Name: 169590-42-5|4-(5-(p-Tolyl)-3-(trifluoromethyl)-1H-pyrazol-1-yl)benzenesulfonamide|98%
Brand: Ambeed
SKU: A180379
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1
[ 720-94-5 ]
[ 17852-52-7 ]
[ 169590-42-5 ]

Yield	Reaction Conditions	Operation in experiment
99%	at 90℃;	General procedure: 4,4,4-Trifluoro-l-(4-methyl-phenyl)-butane-l,3-dione 5 stock solution (7 mL) and (4-Sulfamoylphenyl)hydrazine hydrochloride 6 stock solution (7 mL) were each pumped at a flow rate of 0.125 mL.min 1 into the 2 mL glass mixing chip at room temperature and through the 14 mL PTFE coil heated to 90C. The output of the reactor was collected until no further product was eluted and the solvent removed in vacuo. The solid obtained was suspended in ethyl acetate (30 mL) followed by vacuum filtration. The filtrate was concentrated to obtain a pale yellow solid (0.393 g, 1.0 mmol, 99%). Rf= 0.33 (20% methanol/dichloromethane).
90%	In ethanol;Reflux;	C01 (23.55 g, 102.3 mmol) was refluxed with 4-sulphonamidophenyl hydrazine HCl (23.95 g, 127.9 mmol) in 700 mL ethanol overnight. The reaction was evaporated, dissolved in 700 mL ethyl acetate, washed with water and brine, dried over magnesium sulfate and evaporated to -100 mL ethyl acetate. The product was crystalized by the addition of ~ 400 mL isooctane. After 15 minutes, the white crystalline solid was broken up, washed with isooctane and dried under vacuum (35.15 g, 90% yield). 1H NMR (400 MHz, CDC13) delta 7.94-7.91 (m, 2H), 7.51-7.49 (m, 2H), 7.21-7.20 (m, 2H), 7.15-7.13 (m, 2H), 6.77 (s, 1H), 2.41 (s, 3H). LC tr=4.27 minutes (C-18 column, 5 to 95% acetonitrile/water over 6 minutes at 1.7 mL/min with detection 254 nm, at 23 C). ES(neg)MS m/z 380 (M-H calcd for C17H14F3N302S requires 380).
80%	In ethanol; for 20h;Reflux;	A suspension of 2.21 g (9.61 mmol) 3 and 2.36 g (10.57 mmol) 4-hydrazinylbenzensulfonamidehydrochloride, 5, in 25 mL abs. EtOHwas refluxed for 20 h. The resulting solution was concentrated in vaccum. Theresidue was dissolved in 50 mL ethyl acetate, washed with water (2 x 50 mL) andbrine (50 mL). The organic phase was dried over Na2SO4, filtrated andconcentrated in vacuum. The crude product was purified by column chromatographyeluting with n-hexane and ethyl acetate (2:1) to afford 2.91 g (80%) Celecoxib. Modified ADDIN EN.CITEPenning1997111117ThomasD. PenningJohn J.TalleyStephen R.BertenshawJeffery S.CarterPaul W. CollinsStephenDocterMatthew J.GranetoLen F.LeeJames W.MalechaJulie M.MiyashiroRoland S.RogersD. J.RogierStella S. YuGaryD. AndersonEarl G.BurtonJ. NitaCogburnSusan A.GregoryCarol M.KoboldtWilliam E.PerkinsKarenSeibertAmy W. VeenhuizenYanY. ZhangPeter C.IsaksonSynthesisand Biological Evaluation of the 1,5-Diarylpyrazole Class of Cyclooxygenase-2Inhibitors: Identification of4-[5-(4-Methylphenyl)-3-(trifluoromethyl)-1H-pyrazol-1-yl]benzenesulfonamide(SC-58635, Celecoxib)J. Med.Chem.J.Med.Chem.1347-13654091997[2] 1H-NMR(250 MHz, CDCl3): delta = 7.89 (d, 2H, J = 8.9 Hz, 2H,6H-Ph),7.46 (d, 2H, J = 8.9 Hz, 3H,5H-Ph), 7.14 (pq, 4H, J1 = 8.0 Hz, J2 = 8.3 Hz, Tolyl), 6.74 (s,1H, Pyr), 5.03 (s, 2H, SO2-NH2),2.37 (s, 3H, -CH3). Mp = 159.6 C, m/z = 382.2 [M+H]+

46%	In ethanol; for 24h;Heating / reflux;	To the dione from Step 1 (4. 14 g, 18. 0 mmol) in 75 mL absolute ethanol, 4.26 g (19.0 mmol) 4-sulphonamidophenylhydrazine hydrochloride was added. The reaction was refluxed under argon for 24 hours. After cooling to room temperature and filtering, the reaction mixture was concentrated to afford 6.13 g of an orange solid. The solid was recrystallized from methylene chloride/hexane to give 3.11 g (8.2 mmol, 46%) of the product as a pale yellow solid, having a melting point (mp) of 157 -159 C ; and a calculated composition of C17 H14 N3 2 SF3 ; C, 53.54 ; H, 3.70 ; N, 11.02. The composition that was found by analysis was: C, 53.17 ; H, 3.81 ; N, 10.90.
46%	In ethanol; for 24h;Heating / reflux;	To the dione from Step 1 (4. 14 g, 18.0 mmol) in 75 mL absolute ethanol, 4.26 g (19.0 mmol) 4-sulphonamidophenylhydrazine hydrochloride was added. The reaction was refluxed under argon for 24 hours. After cooling to room temperature PC26183 46 and filtering, the reaction mixture was concentrated to afford 6.13 g of an orange solid. The solid was recrystallized from methylene chloride/hexane to give 3. 11 g (8. 2 mmol, 46%) of the product as a pale yellow solid, having a melting point (mp) of 157-159C ; and a calculated composition of C17 H14 N3 02 SF3 ; C, 53.54 ; H, 3. 70 ; N, 11.02. The composition that was found by analysis was: C, 53.17 ; H, 3.81 ; N, 10.90.
46%	In ethanol; for 24h;Heating / reflux;	Step 2: Preparation of 4-[5-(4-methylphenyl)-3-(trifluoromethyl)-1H-pyrazol-1-yl]benzenesulfonamide. To the dione from Step 1 (4.14 g, 18.0 mmol) in 75 mL absolute ethanol, 4.26 g (19.0 mmol) 4-sulphonamidophenylhydrazine hydrochloride was added. The reaction was refluxed under argon for 24 hours. After cooling to room temperature and filtering, the reaction mixture was concentrated to afford 6.13 g of an orange solid. The solid was recrystallized from methylene chloride/hexane to give 3.11 g (8.2 mmol, 46%) of the product as a pale yellow solid, having a melting point (mp) of 157-159 C.; and a calculated composition of C17H14N3O2SF3; C, 53.54; H, 3.70; N, 11.02. The composition that was found by analysis was: C, 53.17;H, 3.81; N, 10.90.
46%	In ethanol; for 24h;Heating / reflux;	Step 2: Preparation of 4-[5-(4-methylphenyl)-3-(trifluoromethyl)-1H-pyrazol-1-yl]benzenesulfonamide. To the dione from Step 1 (4.14 g, 18.0 mmol) in 75 mL absolute ethanol, 4.26 g (19.0 mmol) 4-sulphonamido-phenylhydrazine hydrochloride was added. The reaction was refluxed under argon for 24 hours. After cooling to room temperature and filtering, the reaction mixture was concentrated to afford 6.13 g of an orange solid. The solid was recrystallized from methylene chloride/hexane to give 3.11 g (8.2 mmol, 46%) of the product as a pale yellow solid, having a melting point (mp) of 157-159 C.; and a calculated composition of C17H14N3O2SF3; C, 53.54; H, 3.70; N, 11.02. The composition that was found by analysis was: C, 53.17; H, 3.81; N, 10.90.
46%	In ethanol; for 24h;Heating / reflux;	To the dione from Step 1 (4.14 g, 18.0 mmol) in 75 mL absolute ethanol, 4.26 g (19.0 mmol) 4-sulphonamidophenylhydrazine hydrochloride was added. The reaction was refluxed under argon for 24 hours. After cooling to room temperature and filtering, the reaction mixture was concentrated to afford 6.13 g of an orange solid. The solid was recrystallized from methylene chloride/hexane to give 3.11 g (8.2 mmol, 46%) of the product as a pale yellow solid, having a melting point (mp) of 157-159C ; and a calculated composition of C17 H14 N3 02 SF3 ; C, 53.54 ; H, 3.70 ; N, 11.02. The composition that was found by analysis was: C, 53.17 ; H, 3.81 ; N, 10.90.
46%	In ethanol; for 24h;Heating / reflux;	Step 2: Preparation of 4- [5- (4-methylphenyl)-3- (trifluoromethyl)-1 H-pyrazol-1-yl] benzenesulfonamide. [000203] To the dione from Step 1 (4.14 g, 18.0 MMOL) in 75 mL absolute ethanol, 4.26 g (19.0 MMOL) 4-SULPHONAMIDOPHENYLHYDRAZINE hydrochloride was added. The reaction was refluxed under argon for 24 hours. After cooling to room temperature and filtering, the reaction mixture was concentrated to afford 6.13 g of an orange solid. The solid was RECRYSTALLIZED from methylene chloride/hexane to give 3.11 g (8. 2 MMOL, 46%) of the product as a pale yellow solid, having a melting point (mp) of 157-159C
46%	In ethanol; for 24h;Heating / reflux;	To the dione from Step 1 (4.14 g, 18.0 MMOL) in 75 mL absolute ethanol, 4.26 g (19.0 MMOL) 4-sulphonamidophenylhydrazine hydrochloride was added. The reaction was refluxed under argon for 24 hours. After cooling to room temperature and filtering, the reaction mixture was concentrated to afford 6.13 g of an orange solid. The solid was recrystallized from methylene CHLORIDE/HEXANE to give 3.11 g (8.2 mmol, 46%) of the product as a pale yellow solid, having a melting point (mp) of 157-159C ; and a calculated composition of C17 H14 N3 02 SF3 ; C, 53.54 ; H, 3.70 ; N, 11.02. The composition that was found by analysis was: C, 53.17 ; H, 3.81 ; N, 10.90.
46%	In ethanol; for 24h;Heating / reflux;	To the dione from Step 1 (4.14 g, 18.0 MMOL) in 75 mL absolute ethanol, 4.26 g (19.0 MMOL) 4-SULPHONAMIDOPHENYLHYDRAZINE hydrochloride was added. The reaction was refluxed under argon for 24 hours. After cooling to room temperature and filtering, the reaction mixture was concentrated to afford 6.13 g of an orange solid. The solid was RECRYSTALLIZED from methylene chloride/hexane to give 3.11 g (8.2 MMOL, 46%) of the product as a pale yellow solid, having a melting point (mp) of 157-159C ; and a calculated composition of C17 HR4 N3 02 SF3 ; C, 53. 54 ; H, 3.70 ; N, 11.02. The composition that was found by analysis was: C, 53.17 ; H, 3.81 ; N, 10.90.
46%	In ethanol; for 24h;Heating / reflux;	To the digne from Step 1 (4.14 g, 18.0 mmol) in 75 mL absolute ethanol, 4.26 g (19.0 mmol) 4-sulphonamidophenylhydrazine hydrochloride was added. The reaction was refluxed under argon for 24 hours. After cooling to room temperature and filtering, the reaction mixture was concentrated to afford 6.13 g of an orange solid. The solid was recrystallized from methylene chloride/hexane to give 3.11 g (8.2 mmol, 46%) of the product as a pale yellow solid, having a melting point (mp) of 157-159C ; and a calculated composition of C17 H14 N3 2 SF3 ; C, 53.54 ; H, 3.70 ; N, 11.02. The composition that was found by analysis was: C, 53.17 ; H, 3.81 ; N, 10.90.
		To a 100 mL Morton flask was charged [1G 4-SAPH-HCI] and 20 mL THF. To this slurry, under nitrogen at room temperature, was added 4.5 mL [NAOH] [(1 M] in [H20)] to pH 11.2. The solution turned homogeneous. After 30 minutes the pH of the solution was adjusted to 0.9 with [TRIFLUOROACETIC] acid. At room temperature, 105 mg diketone, in 10 mL THF, was added. Aliquots were taken periodically as the reaction proceeded and analyzed by HPLC on a 4.6 mm, 5 micron Supelco [SUPELCOSILE] LC-DP column. HPLC analysis in all of the following examples was done by the same method. Results are given in table 1 a below.
		A 50 mL [3-NECK] Morton flask was fitted with a thermometer, a reflux condenser and a nitrogen inlet. To this reactor was charged 25 mL isopropanol and [1G] (4.5 [MMOL)] [4-SAPH-HCI,] followed by the addition of 0.5 g triethylamine (4.4 [MMOL)] to free base the 4-SAPH. The reaction mixture was allowed to stir for 15 minutes at room temperature. To the resultant slurry was added 0.87g (9.2 [MMOL)] chloroacetic acid. The mixture was allowed to stir at room temperature for 15 minutes. After this time period, [1 G] (4.3 [MMOL)] diketone was added and the reaction mixture was heated to 60 [C] and held at this temperature for 2.5 hr. An aliquot was taken and analyzed via HPLC. The reaction was repeated with each of the following acids: acetic, [DICHLOROACETIC,] trichoroacetic, and [TRIFLUOROACETIC.] Comparative results are given in table 2 below.
		A 50 mL [3-NECK] Morton flask was fitted with a thermometer, a reflux condenser and a nitrogen inlet. To this reactor was charged 25 mL isopropanol and [1G] (4.5 [MMOL)] [4-SAPH-HCI,] followed by the addition of 0.5 g triethylamine (4.4 [MMOL)] to free base the 4-SAPH. The reaction mixture was allowed to stir for 15 minutes at room temperature. To the resultant slurry was added 0.87g (9.2 [MMOL)] chloroacetic acid. The mixture was allowed to stir at room temperature for 15 minutes. After this time period, [1 G] (4.3 [MMOL)] diketone was added and the reaction mixture was heated to 60 [C] and held at this temperature for 2.5 hr. An aliquot was taken and analyzed via HPLC. The reaction was repeated with each of the following acids: acetic, [DICHLOROACETIC,] trichoroacetic, and [TRIFLUOROACETIC.] Comparative results are given in table 2 below.
		A 50 mL [3-NECK] Morton flask was fitted with a thermometer, a reflux condenser and a nitrogen inlet. To this reactor was charged 25 mL isopropanol and [1G] (4.5 [MMOL)] [4-SAPH-HCI,] followed by the addition of 0.5 g triethylamine (4.4 [MMOL)] to free base the 4-SAPH. The reaction mixture was allowed to stir for 15 minutes at room temperature. To the resultant slurry was added 0.87g (9.2 [MMOL)] chloroacetic acid. The mixture was allowed to stir at room temperature for 15 minutes. After this time period, [1 G] (4.3 [MMOL)] diketone was added and the reaction mixture was heated to 60 [C] and held at this temperature for 2.5 hr. An aliquot was taken and analyzed via HPLC. The reaction was repeated with each of the following acids: acetic, [DICHLOROACETIC,] trichoroacetic, and [TRIFLUOROACETIC.] Comparative results are given in table 2 below.
		A 50 mL [3-NECK] Morton flask was fitted with a thermometer, a reflux condenser and a nitrogen inlet. To this reactor was charged 25 mL isopropanol and [1G] (4.5 [MMOL)] [4-SAPH-HCI,] followed by the addition of 0.5 g triethylamine (4.4 [MMOL)] to free base the 4-SAPH. The reaction mixture was allowed to stir for 15 minutes at room temperature. To the resultant slurry was added 0.87g (9.2 [MMOL)] chloroacetic acid. The mixture was allowed to stir at room temperature for 15 minutes. After this time period, [1 G] (4.3 [MMOL)] diketone was added and the reaction mixture was heated to 60 [C] and held at this temperature for 2.5 hr. An aliquot was taken and analyzed via HPLC. The reaction was repeated with each of the following acids: acetic, [DICHLOROACETIC,] trichoroacetic, and [TRIFLUOROACETIC.] Comparative results are given in table 2 below.
		A 50 mL [3-NECK] Morton flask was fitted with a thermometer, a reflux condenser and a nitrogen inlet. To this reactor was charged 25 mL isopropanol and [1G] (4.5 [MMOL)] [4-SAPH-HCI,] followed by the addition of 0.5 g triethylamine (4.4 [MMOL)] to free base the 4-SAPH. The reaction mixture was allowed to stir for 15 minutes at room temperature. To the resultant slurry was added 0.87g (9.2 [MMOL)] chloroacetic acid. The mixture was allowed to stir at room temperature for 15 minutes. After this time period, [1 G] (4.3 [MMOL)] diketone was added and the reaction mixture was heated to 60 [C] and held at this temperature for 2.5 hr. An aliquot was taken and analyzed via HPLC. The reaction was repeated with each of the following acids: acetic, [DICHLOROACETIC,] trichoroacetic, and [TRIFLUOROACETIC.] Comparative results are given in table 2 below.
		A 100 mL 3-neck Morton flask was fitted with a reflux condenser, a nitrogen inlet, a thermometer and a glass stopper. This setup was purged with nitrogen for 15 min after which time 1 g (4.47 [MMOL)] [4-SAPH-HCI] and 25 mL anhydrous methyl alcohol was charged to the flask. To the slurry was added 0.5 g (4.95 [MMOL)] triethylamine at room temperature. After 15 minutes, 1 g (8.77 [MMOL)] [TRIFLUOROACETIC] acid was added at room temperature. After 15 minutes at room temperature, the reaction mixture was heated to 55 [C,] 1 g solid diketone (4.3 [MMOL)] was added all at once followed by 5 mL methyl alcohol to wash the addition funnel. Aliquots from the reaction mixture were taken and analyzed by HPLC. Results in mole% by-product formed based on celecoxib at reaction completion are show in table 3 below. The reaction was repeated for the following solvents: Ethyl alcohol, n- Propyl alcohol, i-Propyl alcohol, Trifluoroethanol, and t-Butyl alcohol.
		To a 100 mL Morton flask was charged 1.03g 4-SAPH and 20 mL THF. To this slurry, under nitrogen at room temperature, was added 1g NaOMe (25 wt% in [MEOH)] to pH 10.4. The solution turned homogeneous. After 30 minutes the pH of the solution was adjusted to 1.1 with [TRIFLUOROACETIC] acid. At room temperature, 104 mg diketone, in 10 mL THF, was added. Aliquots were taken periodically as the reaction proceeded and analyzed by HPLC. Results are given in table [1B] below.
	In ethanol; for 20h;Inert atmosphere; Reflux;	General procedure: 4-Hydrazinylbenzenesulfonamide hydrochloride (3?HCl) (982 mg, 4.4 mmol) was added to the stirred solution of diketone 2 (4.0 mmol) in EtOH (60 mL). If free base 3 was used to replace 3?HCl, additional HCl (3 N, 2.0 mL) is needed. The mixture was heated to reflux for 20 h. Then the reaction mixture was concentrated in vacuo. The residue was added EtOAc, washed with water, dried, filtered, and concentrated. The crude product was purified by column chromatography on silica gel (12% MeOH/CH2Cl2) to give a white solid 4 in 85 +/- 5% (n = 3) yield, Rf = 0.78-0.82 (10% MeOH/CH2Cl2).
24.06g	With trifluoroacetic acid; In water; isopropyl alcohol; at 55 - 65℃; for 1h;	Take another 500 mL three-necked glass vial, add 50 mL of isopropanol, to a solution of hydrazinobenzenesulfonamide hydrochloride (17.4 g, 0.078, 1101) and trifluoroacetic acid (0.428, 0.0037111001), and the temperature was raised to 55 (after adding reaction solution 3, reaction 111, adding50mL water, the temperature rose to 65 C full solution, cooling 10 C per hour, down to 15 C, pumping, 45 C under reduced pressure drying to get celecoxib eight crystal 24.068, the yield of 85% Ie ^: detection purity of 99.7%.
	In ethanol; for 24h;Heating / reflux;	To the dione from Step 1 (4.14 g, 18.0 mmol) in 75 mL absolute ethanol, 4.26 g (19.0 mmol) 4-sulphonamidophenylhydrazine hydrochloride was added. The reaction was refluxed under argon for 24 hours. After cooling to room temperature and filtering, the reaction mixture was concentrated to afford 6.13 g of an orange solid. The solid was recrystallized from methylene chloride/hexane to give 3.11 g (8.2 mmol, 46%) of the product as a pale yellow solid, having a melting point of 157-159C ; and a calculated composition of C17Hl4N302SF3 ; C, 53.54 ; H, 3.70 ; N, 11.02. The composition that was found by analysis was: C, 53.17 ; H, 3. 81 ; N, 10.90.
	In ethanol; for 24h;Heating / reflux;	To the dione from Step 1 (4.14 g, 18.0 mmol) in 75 mL absolute ethanol, 4.26 g (19.0 mmol) 4-sulphonamidophenylhydrazine hydrochloride was added. The reaction was refluxed under argon for 24 hours. After cooling to room temperature and filtering, the reaction mixture was concentrated to afford 6.13 g of an orange solid. The solid was recrystallized from methylene chloride/hexane to give 3.11 g (8.2 mmol, 46%) of the product as a pale yellow solid, having a melting point of 157-159C ; and a calculated composition of C17Hl4N302SF3 ; C, 53.54 ; H, 3.70 ; N, 11.02. The composition that was found by analysis was: C, 53.17 ; H, 3. 81 ; N, 10.90.

Reference： [1]Patent: WO2019/64139,2019,A1 .Location in patent: Page/Page column 15-17
[2]Patent: WO2014/12074,2014,A2 .Location in patent: Paragraph 00209; 00210
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[8]Patent: WO2005/49014,2005,A1 .Location in patent: Page/Page column 137-138
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[10]Patent: US2005/14729,2005,A1 .Location in patent: Page 64
[11]Patent: US2005/187172,2005,A1 .Location in patent: Page/Page column 62
[12]Patent: WO2005/84654,2005,A2 .Location in patent: Page/Page column 184
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2
[ 108-24-7 ]
[ 169590-42-5 ]
N-[[4-[5-(4-methylphenyl)-3-(trifluoromethyl)-1H-pyrazol-1-yl]phenyl]sulfonyl]acetamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
84%	With pyridine; dmap at 23℃; for 14h;
	With triethylamine In dichloromethane at 20℃; for 24h;

Reference： [1]Pham, Manh V.; Ye, Baihua; Cramer, Nicolai [Angewandte Chemie - International Edition, 2012, vol. 51, # 42, p. 10610 - 10614,5][Angewandte Chemie, 2012, vol. 124, # 42, p. 10762 - 10766,5] Pham, Manh V.; Ye, Baihua; Cramer, Nicolai [Angewandte Chemie - International Edition, 2012, vol. 51, # 42, p. 10610 - 10614][Angew. Chem., 2012, vol. 124, # 42, p. 10762 - 10766,5]
[2]Pal, Manojit; Madan, Manjula; Padakanti, Srinivas; Pattabiraman, Vijaya R.; Kalleda, Srinivas; Vanguri, Akhila; Mullangi, Ramesh; Mamidi, N. V. S. Rao; Casturi, Seshagiri R.; Malde, Alpeshkumar; Gopalakrishnan; Yeleswarapu, Koteswar R. [Journal of Medicinal Chemistry, 2003, vol. 46, # 19, p. 3975 - 3984]

3
[ 123-62-6 ]
[ 169590-42-5 ]
N-((4-(5′-(p-tolyl)-3′-(trifluoromethyl)-1H-pyrazol-1′-yl)phenyl)sulfonyl)propionamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
90.4%	With triethylamine In tetrahydrofuran for 4h; Heating / reflux;	1 Example 1 Preparation of 4-[5-(4-methylphenyl)-3-(trifluoromethyl)-1H-pyrazol-1-yl]-N-propionylbenzenesulfonamide. Celecoxib (4-[5-(4-methylphenyl)-3-(trifluoromethyl)-1H-pyrazol-1-yl]benzenesulfonamide) (0.2 mol, 76.3 g), tetrahydrofuran (300 ml), propionic anhydride (0.4 mol, 52.1 g), triethylamine (0.22 mol, 22.3 g), and 4-dimethylaminopyridine (0.02 mol, 2.44 g) were stirred at reflux for 4 h.The mixture was concentrated, dissolved in ethyl acetate and washed successively with hydrochloric acid (1N), brine, and water.After drying over magnesium sulfate and concentrating under high vacuum, the mixture was dissolved in ethanol and stirred for 4 h.A white solid was collected by filtration (79.1 g, 90.4%). mp 88.3-96.7° C. Anal. Calculated for C20H18N3SO3F3: C, 54.91; H, 4.15; N, 9.61. Found: C, 54.84; H, 4.23; N, 9.52. 1H NMR (D6-acetone): 11.6 (brs, 1H), 8.06 (d, 2H), 7.59 (d, 2H), 7.23 (s, 4H), 6.99 (s, 1H), 2.8 (m, 2H), 0.98 (t, 3H).
	With triethylamine In dichloromethane at 20℃; for 24h;

Reference： [1]Current Patent Assignee: PFIZER INC - US2004/92566, 2004, A1 Location in patent: Page/Page column 8-9
[2]Pal, Manojit; Madan, Manjula; Padakanti, Srinivas; Pattabiraman, Vijaya R.; Kalleda, Srinivas; Vanguri, Akhila; Mullangi, Ramesh; Mamidi, N. V. S. Rao; Casturi, Seshagiri R.; Malde, Alpeshkumar; Gopalakrishnan; Yeleswarapu, Koteswar R. [Journal of Medicinal Chemistry, 2003, vol. 46, # 19, p. 3975 - 3984]

4
[ 169590-42-5 ]
Carboxy-Celecoxib [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
87%	With potassium permanganate; sodium hydroxide In water at 20℃;	Synthesis of 4-[1-(4-aminosulfonylphenyl)-3-(trifluoromethyl)-1Hpyrazol-5-yl]benzoic acid (2) A mixture of 4-[5-(4-methylphenyl)-3-(trifluoromethyl)-1H-pyrazol-1-yl]benzenesulfonamide (1) (0.5 g, 1.311 mmol), sodium hydroxide (0.056 g, 1.311 mmol) and water (100 mL) was stirred at ambient temperature for 20 min followed by addition of potassium permanganate (0.036 g, 2.25 mmol). After completion of the reaction (as indicated by TLC), the reaction mixture was filtered off at a pump to remove the precipitated manganese dioxide followed by decolourisation of the filtrate with sodium metabisulphite solution (10% w/v). The filtrate was acidified to Congo red to get the precipitated 4-[1-(4-aminosulfonylphenyl)-3-(trifluoromethyl)-1H-pyrazol-5-yl]benzoic acid (2), which was filtered off, washed with distilled water and dried. The precipitate was crystallised from ethanol as: White crystalline powder; m.p. 246 °C; IR (KBr): 2972, 1679, 1090 cm-1;1H NMR (DMSO-d6): δ2.27 (s, 3H, CH3), 7.41 (s, 1H, ArH), 7.49-7.53 (m, 6H, ArH), 7.87 (d, J = 8.1 Hz, 2H, NH2), 12.81 (s, 1H, OH). Anal. calcd for C17H12F3N3O4S: C, 49.64; H, 2.94; N, 10.22; found:C, 49.60; H, 2.97; N, 10.25%. MS m/z [M + H]+: 412.08.
66%	With potassium permanganate; sodium hydroxide In water for 6h; Reflux;	To0.51 g (1.32 mmol) 1, 0.42 g (2.65mmol) potassium permanganate in 10 mL water 0.52 mL 2M sodium hydroxide wereadded and heated to reflux for 6 h. The cooled, brown suspension was filtratedand washed with water. The filtrate was acidified with 2M hydrochloric acid andthe white voluminous preticipate was collected and dried in vacuum affording0.36 g (66%) carboxylic acid. Modified ADDIN EN.CITEBigelow1921181817LuciusA. BigelowASTUDY OF SIDE-CHAIN OXIDATIONS WITH POTASSIUM PERMANGANATE.IIJ. Am. Chem.Soc.J.Am. Chem. Soc.2010-20194491921[3]. 1H-NMR (300 MHz, DMSO-d6): δ = 13.3 (br s, 1H, -COOH),7.94 (d, 2H, J = 8.3 Hz, 2H,6H-Ph),7.88 (d, 2H, J = 8.6 Hz, 2H,6H-Ph-COOH),7.56 (d, 2H, J = 8.6 Hz, 3H,5H-Ph),7.51 (s, 2H, -SO2NH2),7.44 (d, 2H, J = 8.3 Hz, 3H,5H-Ph-COOH),7.34 (s, 1H, Pyr), Mp = 243 °C, m/z =410.1 [M-H]-
66%	With potassium permanganate; sodium hydroxide In water for 6h; Reflux; Inert atmosphere;	To 0.51 g (1.32 mmol) Celecoxib, 0.42 g (2.65 mmol) potassiumpermanganate in 10mL water 0.52 mL 2M sodium hydroxide wereadded and heated to reflux for 6 h. The cooled, brown suspensionwas filtrated and washed with water. The filtrate was acidified with2M hydrochloric acid and the white voluminous preticipate wascollected and dried in vacuum affording 0.36 g (66%) carboxylic acidB15.1H NMR (400 MHz, Chloroform-d) d 8.05-7.97 (m, 2H), 7.85 (d,J = 8.2 Hz, 2H), 7.37 (d, J = 8.1 Hz, 2H), 7.26 (d, J = 8.0 Hz, 2H), 6.79(s, 1H), 4.94-4.74 (m, 2H), 2.46 (t, J = 2.3 Hz, 1H). ESI-HRMS (m/z):calcd. for C17H13F3N3O4S [MH]: 412.0579; found 412.0658,C17H12F3N3KO4S [MNa]: 450.0138; found 450.0138.

65%	With cerium(III) chloride; 1,1,1-trichloroethanol; oxygen In acetonitrile at 60℃; Irradiation;
	Multi-step reaction with 2 steps 1.1: NBS / Irradiation 1.3: sodium borohydride 2.1: Jones's chromic acid / acetone
	Multi-step reaction with 3 steps 1: NBS / benzene / 3 h / Irradiation 2: H₂O / acetone / 120 h / Heating 3: 46 percent / 1.33M Jones reagent / acetone
	With potassium permanganate; sodium hydroxide In water at 20℃;	Synthesis of 4-{1-[4-(aminosulfonyl)phenyl]-3-(trifluoromethyl)-1H-pyrazol-5-yl}benzoic acid (2) A mixture of 4-[5-(4-methylphenyl)-3-(trifluoromethyl)-1H-pyrazol-1-yl]benzenesulfonamide (1) (0.5g, 1.31mmol), sodium hydroxide (0.056g, 1.31mmol) and water (100ml) was stirred at ambient temperature for 20min followed by addition of potassium permanganate (0.036g, 2.25mmol). After completion of the reaction (as indicated by TLC), reaction mixture was filtered off at pump to remove the precipitated manganese dioxide followed by decolorization of the filtrate with sodium metabisulfite solution. Filtrate was acidified to get the precipitated 4-{1-[4-(aminosulfonyl)phenyl]-3-(trifluoromethyl)-1H-pyrazol-5-yl}benzoic acid (2), which was filtered, washed with distilled water and dried. The precipitates were crystallized from ethanol. White powder; M.p. 246°C. IR (KBr) cm-1: 2972, 1679, 1090 1H NMR (DMSO-d6, 400MHz) δ: 2.27 (s, 3H, CH3), 7.41 (s, 1H, ArH), 7.49-7.53 (m, 6H, ArH), 7.87(d, J=8.1Hz, 2H, NH2), 12.81 (s, 1H, OH) Anal. Calculated for C17H12F3N3O4S: C, 49.64, H, 2.94, N, 10.22; Found: C, 49.6, H, 2.97, N, 10.25; MS m/z [M+H]+ : 412.08.

Reference： [1]Mustafa, Ghulam; Zia-Ur-Rehman, Muhammad; Khan, Islam Ullah; Ishtiaq, Saiqa; Hussain, Sajjad; Arshad, Muhammad Nadeem; Asiri, Abdullah Mohammad [Journal of Chemical Research, 2016, vol. 40, # 3, p. 167 - 172]
[2]Lill, Andreas; Scholich, Klaus; Stark, Holger [Tetrahedron Letters, 2013, vol. 54, # 49, p. 6682 - 6686]
[3]Li, Jili; Zhang, Jinlong; Zhang, Qiuping; Bai, Zhongjie; Zhao, Quanyi; Wang, Zhen; Chen, Yonglin; Liu, Bin [Journal of Organometallic Chemistry, 2018, vol. 874, p. 49 - 62]
[4]Wang, Chang-Cheng; Zhang, Guo-Xiang; Zuo, Zhi-Wei; Zeng, Rong; Zhai, Dan-Dan; Liu, Feng; Shi, Zhang-Jie [Science China Chemistry, 2021, vol. 64, # 9, p. 1487 - 1492]
[5]Paulson; Zhang; Jessen; Lawal; Liu; Dudkowski; Wang; Chang; Yang; Findlay; Berge; Markos; Breau; Hribar; Yuan [Xenobiotica, 2000, vol. 30, # 7, p. 731 - 744]
[6]Penning, Thomas D.; Talley, John J.; Bertenshaw, Stephen R.; Carter, Jeffery S.; Collins, Paul W.; Docter, Stephen; Graneto, Matthew J.; Lee, Len F.; Malecha, James W.; Miyashiro, Julie M.; Rogers, Roland S.; Rogier; Yu, Stella S.; Anderson, Gary D.; Burton, Earl G.; Cogburn, J. Nita; Gregory, Susan A.; Koboldt, Carol M.; Perkins, William E.; Seibert, Karen; Veenhuizen, Amy W.; Zhang, Yan Y.; Isakson, Peter C. [Journal of Medicinal Chemistry, 1997, vol. 40, # 9, p. 1347 - 1365]
[7]Mustafa, Ghulam; Angeli, Andrea; Zia-ur-Rehman, Muhammad; Akbar, Nosheen; Ishtiaq, Saiqa; Supuran, Claudiu T. [Bioorganic Chemistry, 2019, vol. 91]

5
[ 720-94-5 ]
[ 169590-42-5 ]

Yield	Reaction Conditions	Operation in experiment
	In water; isopropyl alcohol;	Step b 4-[5-(4-Methylphenyl)-3-(trifluoromethyl)-1H-pyrazol-1-yl]benzenesulfonamide 1-(4-Methylphenyl)-4,4,4-trifluorobutane-1,3-dione (4.14 g) from step a was stirred in isopropanol (75 ml). 4-sulphonamidophenylhydrazine hydrochloride (4.25 g) was added. The reaction mixture was refluxed under nitrogen atmosphere for 24 hours, cooled to room temperature and filtered, The filtrate was treated with activated carbon at 40-45 C. The product was crystallized by adding water (150 ml). The product was recrystallized from isopropanol and water.
3.11 g (8.2 mmol, 46%)	In ethanol;	Step 2 Preparation of 4-[5-(4-methylphenyl)-3-(trifluoromethyl)-1H-pyrazol-1-yl]benzenesulfonamide To the dione from Step 1 (4.14 g, 18.0 mmol) in 75 mL absolute ethanol was added 4.26 g (19.0 mmol) 4-sulphonamidophenylhydrazine hydrochloride. The reaction was refluxed under argon for 24 hours. After cooling to room temperature and filtering, the reaction mixture was concentrated to afford 6.13 g of an orange solid. The solid was recrystallized from methylene chloride/hexane to give 3.11 g (8.2 mmol, 46%) of the product as a pale yellow solid: mp 157-159 C.; Anal. calc'd for C17 H14 N3 O2 SF3: C, 53.54; H, 3.70; N, 11.02. Found: C, 53.17; H, 3.81; N, 10.90.
3.11 g (8.2 mmol, 46%)	In ethanol;	Step 2: Preparation of 4-[5-(4-methylphenyl)-3-(trifluoromethyl)-1H-pyrazol-1-yl]benzenesulfonamide To the dione from Step 1 (4.14 g, 18.0 mmol) in 75 mL absolute ethanol was added 4.26 g (19.0 mmol) 4-sulphonamidophenylhydrazine hydrochloride. The reaction was refluxed under argon for 24 hours. After cooling to room temperature and filtering, the reaction mixture was concentrated to afford 6.13 g of an orange solid. The solid was recrystallized from methylene chloride/hexane to give 3.11 g (8.2 mmol, 46%) of the product as a pale yellow solid: mp 157-159 C.; Anal. calc'd for C17 H14 N3 O2 SF3: C, 53.54; H, 3.70; N, 11.02. Found: C, 53.17; H, 3.81; N, 10.90.

	In water; ethyl acetate; at 0 - 80℃; for 6h;Product distribution / selectivity;	A mixture of 4-Sulphonamidophenylhydrazine hydrochloride (10.5 g), 4,4,4-trifluoro-1-[4-(methyl)phenyl]butane-1,3-dione (10.5 g), ethyl acetate (50 ml) and water (50 ml) was heated at 75-80 C. and stirred for 5 hours. The reaction mixture was cooled to 0-5 C. and stirred for 1 hour. The separated solid was filtered, washed with water (150 ml) and dried (Yield: 27 g).
	In methanol; at 65℃; for 10h;Product distribution / selectivity;	A mixture of 4-sulphonamidophenylhydrazine hydrochloride (42.2 g), 4,4,4-trifluoro-1-[4-(methyl)phenyl]butane-1,3-dione (40 g) and methanol (860 ml) was heated to 65 C. and stirred for 10 hours. The reaction mixture was cooled to 25-30 C. and the solvent was completely removed under vacuum. The residue was taken in a mixture of ethyl acetate (332 ml) and water (80 ml) and stirred for 10 minutes. The layers were separated and the aqueous layer was extracted with ethyl acetate (2×52 ml). The organic layers were combined and washed with water (2×80 ml). The combined organic layer was treated with activated carbon at 60 C. The carbon was removed by filtration and the solvent was distilled off to a volume of about 100-115 ml and n-hexane (320 ml) was added. The reaction mixture was stirred at 30 C. for 30 minutes. The separated solid was filtered and washed with n-hexane (20 ml) (Yield: 55 g, purity 94.3%).

Reference： [1]Patent: US2002/16351,2002,A1
[2]Patent: US5756529,1998,A
[3]Patent: US5760068,1998,A
[4]Patent: US2008/234491,2008,A1 .Location in patent: Page/Page column 4
[5]Patent: US2008/234491,2008,A1 .Location in patent: Page/Page column 4
[6]Chemistry - A European Journal,2019,vol. 25,p. 8903 - 8910

6
[ 169590-42-5 ]
C₁₇H₁₄F₃N₃O₂S^(1-)*Na⁽¹⁺⁾ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Stage #1: 4-[5-(4-(methyl)phenyl)-3-(trifluoromethyl)-1H-pyrazol-1-yl]benzenesulphonamide With sodium hydroxide; water at 60℃; Stage #2: In ethanol at 60℃;	1; 3; 6 Example 1; Celecoxib sodium salt from aqueous solution To 77.3 mg of commercially-available celecoxib was added 1.0 mL distilled water, followed by 0.220 mL of 1 M [NAOH] (VWR). The mixture was heated with stirring to [60°C,] whereupon an additional 1.0 mL distilled water was added. Solid [NAOH] (22 mg) was added, and the solid [NAOH] and celecoxib dissolved. The mixture was heated again at [60°C] to evaporate water. About 15 mL reagent-grade ethanol was added, while the mixture was stirred and heated at [60°C] with air blowing over the solution. Heating continued until the solution was dry. The resulting material was analyzed by powder x-ray diffraction (PXRD), differential scanning calorimetry (DSC), and thermogravimetric analysis (TGA), the results of which are seen in Figs. 1-3. The product was found to contain about 4.1 equivalents of water per equivalent of salt, although most of all of the water could be contained in the [NAOH] that co-precipitated with the salt. For the DSC analysis, the purge gas used was dry nitrogen, the reference material was an empty aluminum pan that was crimped, and the sample purge was 50 mL/minute. DSC analysis of the sample was performed by placing 2.594 mg of sample in an aluminum pan with a crimped pan closure. The starting temperature was [20°C] with a heating rate of [10°C/MINUTE,] and the ending temperature was 200°C. The resulting DSC analysis is shown in Fig. 1. The transitions observed include a melt/dehydration process between about 40 and about 70 C, another transition between about 70 and about 100 C possibly resulting from a [RECRYSTALLIZATION/PRECIPITATION] event and a second melt/dehydration transition between about 100 and about 110 C. For all of the TGA experiments, the purge gas used was dry nitrogen, the balance purge was 40 mL/minute N2, and the sample purge was 60 [ML/MINUTE] N2. TGA of the sample was performed by placing 2.460 mg of sample in a platinum pan. The starting temperature was [20°C] with a heating rate of [10°C/MINUTE,] and the ending temperature was [300°C.] The resulting TGA analysis is shown in Fig. 2. The TGA shows a mass loss of about 12.5% between about 30 and about [50] C, attributed to the loss of about 2.8 water molecules. A second mass loss of about 2.0% between about 71 and 85 C, attributed to the loss of about 0.5 water molecules. Finally, a mass loss of about 4. [0%] between about 148 and 170 C attributed to either the loss of about 1 water molecule or some decomposition of the drug compound. The hydration state of the salt can vary depending on the humidity, temperature and other conditions. The PXRD pattern for the compound prepared above is shown in Fig. 3. In the diffractogram of Fig. 3, the background has been removed. The PXRD pattern has characteristic peaks that can be used to characterize the salt comprising any one, or any combination of any two, any three or any four peaks or any other combination of peaks at a 2-theta angle of Fig. 3 including for example, the peaks at 6. [40°,] 7. [01°,] 16. [73°,] and 20. [93°.]Example 3. Celecoxib sodium salt from aqueous solution. Synthesis 1 : To a vial was added 29.64 mg celecoxib and 3.00 mL of 1 N sodium hydroxide. The celecoxib dissolved immediately. After [A] time, the celecoxib precipitated from solution. Synthesis 2 : TO a vial was added 7.10 mg celecoxib and 3.00 mL of 1 N sodium hydroxide. The celecoxib dissolved. Overnight, the celecoxib precipitated and formed white, needle-like crystals. Synthesis 3 : To a vial was added 17.6 mg celecoxib and 10 mL of 1 N sodium hydroxide. The celecoxib dissolved. The vial was placed in a beaker wrapped in aluminum foil and filled with a large tissue for insulation. The beaker was left and crystals formed within about 12-36 hours. Analysis : The product solids from syntheses 1 and 2 were combined and analyzed by PXRD, DSC, and TGA as in example 1, but a 0.5 mm capillary was used to hold the sample in the PXRD experiment. The product salt was found to contain about 4 equivalents of water per equivalent of salt, although as stated herein the hydration state of the salt can vary depending on humidity, temperature, and other conditions. TGA showed a weight loss of 14.9% as the temperature was increased from room temperature to 100C at 10C/MIN. DSC analysis showed a large endothermic transition at 74+/-1. 0C and a second broad and noisy endothermic transition at about 130+/-5. 0C. The PXRD pattern has peaks that can be used to characterize the salt include any one or combination comprising any two, any three, any four, any five, or all six 2-theta angle peaks of 3. [6,] 8. [9,] 9. [6,] 10. [8,] 11. [4,] [AND20. 0.]Example 6 Preparation of Celecoxib Sodium The free acid of Celecoxib 5.027 g was suspended in an aqueous solution OF NAOH (13.181 mL, 1 M). The suspension was gently heated at 60C for 1 minute to dissolve the remaining solid. The mixture was allowed to cool to room temperature, which yielded no precipitation. Further cooling in an ice bath for 1 hour gives precipitation of the product. The resulting solution was filtered and allowed to air dry. Characterization of the product has been achieved via TGA, DSC, PXRD, Raman spectroscopy, microscopy, [AND'H NNR] spectroscopy. NMR acquisitions were performed on a Varian 300 MHz Spectrometer in (methyl [SULFOXIDE)-D6.] The PXRD pattern has characteristic peaks as shown in Fig. 13A. An intense peak can be seen at 19.85 with other peaks at 2-theta angles including but not limited to, 3.57, 10.69, 13.69, 20.43, 21.53 and 22.39. The crystal can be characterized by any one, any two, any three, any four, any five or all six of the peaks above, or any one or combination of any number 2-theta angles of Fig. 13A. Results of Raman spectroscopy can be seen in Fig. 13B. Raman shift [(CM~L)] peaks occur at positions including, but not limited to, any one, any two, any three, any four, all five of 1617.11, 1446.20, 1373.73, 975.02 and 800.15, or any combinations 2,3, 4,5 or more peaks of Fig. 13B.
	With sodium ethanolate In ethanol; isopropyl alcohol	2 Example 2; Celecoxib sodium salt from 2-propanol solution To 126.3 mg of celecoxib (Fako Hazlari) was added a 1.0 mL aliquot of isopropanol, and the mixture was heated to dissolve the celecoxib. Sodium ethoxide was added as a solution 21% in ethanol (0.124 mL solution, 3. [31] x [104] mol sodium ethoxide). An additional 1.0 mL of isopropanol was added. The mixture was stirred to obtain a [SLURRY] of white crystalline solids that appeared as fine birefringent needles by polarized light microscopy. The slurry was filtered by suction filtration and rinsed with 2 mL of isopropanol. The solid was allowed to air dry before being gently ground to a powder. The product was analyzed by PXRD, DSC, and TGA as in Example 1, but a 0.5 mm capillary was used to hold the sample in the PXRD experiment. The compound lost 17.35% weight between room temperature and [120°C.] The DSC trace shows a broad endothermic region, which is consistent with a loss of volatile components with increasing temperature. The endotherm peaks at [66°C.] The PXRD pattern peaks that can be used to characterize the salt include any one or combination comprising any two, any three, any four, any five, any six, any seven, any eight, any nine, any ten, any eleven, any twelve, or all thirteen 2-theta angles of 4.09°, 4.99°, 6.51°, 7.07°, 9.99°, 11.59°, 16. [53°,] 17. [69°,] 18. [47,] 19. [13', 20. 11',] 20. [95] 22. [67 °,] or any one or combination of 2,3, 4,5, 6,7, 8,9, 10,11, 12, or 13 peaks of Fig. 62.

Reference： [1]Current Patent Assignee: JOHNSON & JOHNSON INC - WO2004/284, 2003, A1 Location in patent: Page 63, 64
[2]Current Patent Assignee: JOHNSON & JOHNSON INC - WO2004/284, 2003, A1 Location in patent: Page 64, 65

7
[ 598-21-0 ]
[ 169590-42-5 ]
[ 1369589-67-2 ]

Yield	Reaction Conditions	Operation in experiment
	With triethylamine In dichloromethane at 0 - 20℃; for 1h;	5.1 N-(Bromoacetyl)-4-[5-(4-methylphenyl)-3-(trifluoromethyl)-1H-pyrazol-1-yl]-benzenesulfonamide To a solution of Celebrex (1.9 g, 5 mmol) and Et3N (0.7 g, 7 mmol) in 30 ml OF CH2Cl2 is added 2-bromoacetyl bromide (1.0 g, 5 mmol) at 0 °C. After 1h of stirring at rt, the reaction mixture is poured into a separatory funnel containing EtOAc (50 mL)/NH4Cl (50 mL, sat). The phases are separated and the aqueous phase is extracted twice with EtOAc (2 * 50 mL). The organic layers are combined, washed with brine, dried over anhydrous NA2SO4 and evaporated to dryness. The crude material can be further purified by flash chromatography eluting with 1: 3 EtOAc/hexanes to yield the title compound.

Reference： [1]Current Patent Assignee: MERCK & CO INC - WO2004/37798, 2004, A1 Location in patent: Page 31-32

8
[ 169590-42-5 ]
[ 258278-55-6 ]
[ 586347-24-2 ]

Yield	Reaction Conditions	Operation in experiment
	With 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride In dichloromethane at 0 - 20℃; for 1h;	3 4-[({4-[5-(4-Methylphenyl)-3-(trifluoromethyl)-1H-pyrazol-1-yl]phenyl}sulfonyl)amino]carbonyl}benzyl nitrate To a solution OF 4-NITROOXYMETHYLBENZOIC acid (1.97 g, 10 mmol) and Celebrex (3.81 g, 10 mmol) in 100 ml OF CH2Cl2 is added EDCI (3.8 g, 20 mmol) at 0 °C. After 1h of stirring at rt, the reaction mixture is poured into a separatory funnel containing EtOAc (50 RNL)/NH4Cl (50 mL, sat). The phases are separated and the aqueous phase is extracted twice with EtOAc (2 * 50 mL). The organic layers are combined, washed with brine, dried over anhydrous NA2SO4 and evaporated to dryness. The crude material can be further purified by flash chromatography eluting with 1: 3 EtOAc/hexanes to yield the title compound.

Reference： [1]Current Patent Assignee: MERCK & CO INC - WO2004/37798, 2004, A1 Location in patent: Page 30

9
[ 169590-42-5 ]
[ 2949-22-6 ]
[ 693260-03-6 ]

Yield	Reaction Conditions	Operation in experiment
88.1%	With 1,8-diazabicyclo[5.4.0]undec-7-ene In chloroform at 20℃; for 6h;	3.a a. Synthesis of Ethylamino COX-2 (EA- COX-2) [0188] The COX-2 enzyme is a disease angiogenic target that can be targeted with ECCOX-2, a compound of the present invention. N-4-(5-p-tolyl-3-trifluoromethyl-pyrazol-1-yl)benzenesulfonylamide (COX-2 inhibitor) (114.4 mg, 0.3 mmol) was dissolved in chloroform (2 ml). To this solution, DBU 44.9 μl (0.3 mmol in chloroform 0.5 ml) and ethyl isocyanatoacetate 33.7 μl (0.3 mmol in chloroform 0.5 ml) were added. The reaction was stirred at room temperature for 6 hours. The solvent was evaporated under vacuo. The product was isolated from silica gel-packed column using chloroform/methanol as an eluant. The yield of the ester form of COX-2 (compound I) was 135 mg (88.1%). The synthetic scheme is shown in FIG. 13. NMR spectra data was recorded in FIG. 14. [0189] Compound I (102 mg, 0.2 mmol) was dissolved in 2 ml of methanol and ethylene diamine (72.9 μl) was added. The reaction was stirred at room temperature for 24 hours. The product was isolated from silica gel-packed column using chloroform/methanol as an eluant. The desired ethylamino COX-2 (EA- COX-2) (compound II) was isolated (91 mg, 86.7% yield). NMR spectra data of compound II was recorded in FIG. 15.
88.1%	With 1,8-diazabicyclo[5.4.0]undec-7-ene In chloroform at 20℃; for 6h;	3.a The COX-2 enzyme is a disease angiogenic target that can be targeted with EC-celecoxib, a compound of the present invention. N-4-(5-p-tolyl-3-trifluoromethyl-pyrazol-1-yl)benzenesulfonylamide (celecoxib) (114.4 mg, 0.3 mmol) was dissolved in chloroform (2 ml). To this solution, DBU 44.9 μl (0.3 mmol in chloroform 0.5 ml) and ethyl isocyanatoacetate 33.741 (0.3 mmol in chloroform 0.5 ml) were added. The reaction was stirred at room temperature for 6 hours. The solvent was evaporated under vacuo. The product was isolated from silica gel-packed column using chloroform/methanol as an eluant. The yield of the ester form of celecoxib (compound I) was 135 mg (88.1%). The synthetic scheme is shown in FIG. 13. NMR spectra data was recorded in FIG. 14. Compound I (102 mg, 0.2 mmol) was dissolved in 2 ml of methanol and ethylene diamine (72.9 μl) was added. The reaction was stirred at room temperature for 24 hours. The product was isolated from silica gel-packed column using chloroform/methanol as an eluant. The desired ethylamino celecoxib (EA-celecoxib) (compound II) was isolated (91 mg, 86.7% yield). NMR spectra data of compound II was recorded in FIG. 15.
82%	With 1,8-diazabicyclo[5.4.0]undec-7-ene In chloroform at 20℃; for 3h;	2 381.4 mg (1.0 mmol) of Celebrex (BZF, 4-[5-(4-methylphenyl)-3-(trifluoromethyl)-1-pyrazol-1-yl]-Benzenesulfonamide) and 152.4 mg (11.0 mmol) of DBU (1,8-diazabicyclo[5.4.0]undec-7-ene) were dissolved in 10 ml of chloroform. 129.1 mg (1.0 mmol) of ethyl isocyanatoacetate in 5 ml chloroform was then added dropwisely. The mixture was stirred for 3 hours at room temperature. The solvent was evaporated in vacuo and the crude product was loaded onto a silica gel packed column (mobile phase: chloroform and methanol gradient). The product (418.6 mg, white solid) was then isolated as (82% yield). Synthetic scheme of GAP-Coxi is shown in FIG. 12. Proton NMR of BZF and COXi-OEt confirmed the respective structures (FIG. 13).

Reference： [1]Current Patent Assignee: CELL POINT; THE UNIVERSITY OF TEXAS SYSTEM - US2004/166058, 2004, A1 Location in patent: Page/Page column 13
[2]Current Patent Assignee: THE UNIVERSITY OF TEXAS SYSTEM - US2005/129619, 2005, A1 Location in patent: Page/Page column 14
[3]Current Patent Assignee: THE UNIVERSITY OF TEXAS SYSTEM - US2006/246005, 2006, A1 Location in patent: Page/Page column 26-27

10
[ 24424-99-5 ]
[ 169590-42-5 ]
[ 850828-49-8 ]

Yield	Reaction Conditions	Operation in experiment
87%	With dmap; triethylamine In dichloromethane at 20℃;	11 To a suspension of 4- [5- (4-methylphenyl)-3- (trifluoro- methyl)-lH-pyrazol-1-yl] benzenesulfonamide (6.93 g, 18.2 mmol) in dichloromethane (70 ml) were added dimethylamino- pyridine (0.22 g, 1.82 mmol) and triethylamine (3.80 ml, 27.3 mmol) at room temperature. Thereto was added dropwise a solution of di-tert-butyl dicarbonate (4.76 g, 21.8 mmol) in dichloromethane (70 ml) at room temperature, and the mixture was stirred overnight. The reaction mixture was concentrated under reduced pressure, and ethyl acetate and a 20% aqueous oxalic acid solution were added thereto, and the organic layer was separated. The organic layer was washed with water twice and washed with brine, dried over sodium sulfate and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (hexane: ethyl acetate = 4: 1-> 3: 1) to give tert butyl ( {4- [5- (4-methylphenyl)-3- (trifluoromethyl)-lH- pyrazol-l-yl] phenyl} sulfonyl) carbamate (7.64 g, 87%) as powders. MS: 499 [M+NH4]+, APCI (10 mM-AcONH4/MeOH)

Reference： [1]Current Patent Assignee: MITSUBISHI CHEMICAL HOLDINGS CORPORATION - WO2005/37271, 2005, A2 Location in patent: Page/Page column 84-85

11
[ 24424-99-5 ]
[ 96-32-2 ]
[ 169590-42-5 ]
[ 473465-06-4 ]

Yield	Reaction Conditions	Operation in experiment
91%	With dmap; potassium carbonate; triethylamine In tetrahydrofuran	3 Preparation of methyl N-(tert-butoxycarbonyl)-N-({4-[5-(4-methylphenyl)-3-(trifluoromethyl)-1H-pyrazol-1-yl]phenyl}sulfonyl)glycinate Preparation of methyl N-(tert-butoxycarbonyl)-N-({4-[5-(4-methylphenyl)-3-(trifluoromethyl)-1H-pyrazol-1-yl]phenyl}sulfonyl)glycinate A mixture of celecoxib (1.00 g, 2.62 mmol), DMAP (0.160 g, (1.31 mmol), di-t-butyl dicarbonate (1.72 g, 7.87 mmol) and triethylamine (0.318 g, 3.14 mmol) in anhydrous THF (10.0 mL) was stirred at room temperature for 1 hour. Methyl bromoacetate (1.00 g, 6.55 mmol) and K2CO3 (0.724 g, 5.24 mmol) was then added and the resulting mixture was stirred at room temperature for 21.5 hours. The reaction mixture was poured into sat. NaHCO3 and extracted with ethyl acetate (2*100 mL). The organic layers were combined, washed with sat. NaCl (50 mL), dried over MgSO4, filtered and concentrated under vacuum. The resulting yellow glass was purified by flash chromatography (silica gel, 9:1 hexanes:ethyl acetate) to afford 1.32 g (91% yield) of the product as a white powder: mp, 88.5° C.; 1H NMR (dmso-d6/300 MHz) δ 8.06 (d, 2H, J=8.7 Hz), 7.61 (d, 2H, J=8.9 Hz), 7.22-7.16 (m, 5H), 4.59 (s, 2H), 3.69 (s, 3H), 2.30 (s, 3H), 1.23 (s, 9H); HRMS (M+H)+calcd. for C25H27F3O6S: 554.1573; found: 554.1601.

Reference： [1]Current Patent Assignee: PFIZER INC - US2003/55012, 2003, A1

12
[ 96-32-2 ]
[ 169590-42-5 ]
[ 473465-08-6 ]

Yield	Reaction Conditions	Operation in experiment
51%	With sodium hydrogencarbonate; potassium carbonate In ethyl acetate; N,N-dimethyl-formamide	4 Preparation of methyl N-(2-methoxy-2-oxoethyl)-N-({4-[5-(4-methylphenyl)-3-(trifluoromethyl)-1H-pyrazol-1-yl]phenyl}sulfonyl)glycinate Preparation of methyl N-(2-methoxy-2-oxoethyl)-N-({4-[5-(4-methylphenyl)-3-(trifluoromethyl)-1H-pyrazol-1-yl]phenyl}sulfonyl)glycinate A mixture of Celecoxib (0.500 g, 1.31 mmol), methyl bromoacetate (0.501 g, 3.28 mmol) and K2CO3 (0.362 g, 2.62 mmol) in anhydrous DMF (5.0 mL) was stirred at room temperature for 21 hours. The mixture was then poured into sat. NaHCO3 (200 mL) and extracted with ethyl acetate (200 mL). The ethyl acetate solution was then washed with sat NaCl (50 mL), dried over MgSO4, filtered and concentrated under vacuum. The crude product was purified by flash chromatography (silica gel, 98:2 methylene chloride:methanol) to afford 0.350 g (51% yield) of the product as a colorless glass: 1H NMR (dmso-d6/300 MHz) δ 7.90 (d, 2H, J=8.7 Hz), 7.53 (d, 2H, J=8.7 Hz), 7.23-7.17 (m, 5H), 4.19 (s, 4H), 3.54 (s, 6H), 2.30 (s, 3H); HRMS (M+NH4)+calcd. for C23H26F3N4O6S: 543.1525; found: 543.1526.

Reference： [1]Current Patent Assignee: PFIZER INC - US2003/55012, 2003, A1

13
[ 383-63-1 ]
4-hydrazinobenzene-1-sulfonamide hydrochloride [ No CAS ]
[ 122-00-9 ]
[ 169590-42-5 ]

Yield	Reaction Conditions	Operation in experiment
	Stage #1: ethyl trifluoroacetate,; para-methylacetophenone With sodium methylate In methanol; isopropyl alcohol at 50 - 55℃; for 2h; Stage #2: 4-hydrazinobenzene-1-sulfonamide hydrochloride With trifluoroacetic acid In methanol; water; isopropyl alcohol at 50 - 55℃; for 2.5h; Stage #3: In methanol; water; isopropyl alcohol at 20 - 65℃; for 14h;	7 Example 7 Preparation of celecoxib with hydrazine reactant containing water To a 250 mL reactor which had been purged with nitrogen and which had been fitted with a mechanical stirrer and a chilled condenser was charged while stirring, isopropyl alcohol (50.75g), ethyltrifluoroacetate (37.95g), sodium methoxide (25% in methanol, 53.28g) and [4'-METHYLACETOPHENONE] (27.43g). The reaction mixture was heated to [50-55C] and held for at least 2 hours. To a separate 1 L reactor which had been purged with nitrogen and fitted with a mechanical stirrer and a chilled condenser, was charged [4-SAPH HCI] (45.96g), isopropyl alcohol [(101.] 2g), water (74g) and [TRIFLUOROACETIC] acid (23.43g). The 4- [SAPH HCI] was heated to [50C] with agitation. At the completion of the 2 hour reaction period, the contents of the first reactor was transferred to the second reactor containing the [4-SAPH HCI] over a period of at least five minutes and the reaction mixture was then brought to [55C] and maintained at that temperature for at least 30 minutes. The pH of the reaction mixture was then adjusted to be within the range of 3 to 9 followed by the addition of water (95g). The contents were then heated to [65C] and the pH was again adjusted to be within the range of 3 to 9. Water (90g) was then added to the mixture over a time period of about 20 minutes while maintaining the temperature at about [65C.] The reaction mixture was then cooled to about [20C] over a period of 12 to 14 hours to produce celecoxib (62-65g) with less than 0.05% regio-isomer and undetectable regioisomer.
	Stage #1: ethyl trifluoroacetate,; para-methylacetophenone With sodium methylate In methanol; isopropyl alcohol at 50℃; for 2h; Stage #2: 4-hydrazinobenzene-1-sulfonamide hydrochloride With trifluoroacetic acid In methanol; isopropyl alcohol at 50 - 55℃; for 1h; Stage #3: With sodium hydroxide In methanol; water; isopropyl alcohol at 20 - 65℃; for 9h;	10 Example 10 Preparation of celecoxib by the addition of 4-SAPH-HCI to diketone To a 1 L reactor fitted with a mechanical stirrer and maintained under a nitrogen atmosphere, was added isopropyl alcohol (54.7g, 0.912 moles), ethyl [TRIFLUOROACETATE] (37.7g, 0.267 moles), and 25% sodium methoxide in methanol (53.3g, 0.247 moles). To the agitated reactor was added 4-methylacetophenone (27.32g, 0.205 moles). The reaction mixture was heated to [50C] and maintained for 2 hours. Trifluoroacetic acid (36.6g, 0.321 moles) was added to the reaction mixture over a period of five minutes. [4-SAPH-HCI] (46. [0G,] 0.205 moles) was added through a power addition funnel over a period of 10 minutes. The reaction mixture was brought to [55C] and maintained for one hour. Isopropyl alcohol (81.5g, 1.36 moles) was added followed by the addition of 50% sodium hydroxide [(18.] 5g, 0.231 moles) to achieve a pH of 7. Water (87.8g, 4.88 moles) was added and the reaction mixture heated to [65C.] Water (90. 0g 5.00 moles) was added over ten minutes. The reaction mixture was cooled to [20C] over nine hours. The slurry was filtered and washed twice with 50% (weight) aqueous isopropyl alcohol (100g). The solid was dried in a vacuum oven for 16 hours to yield celecoxib (67.2g) whose HPLC retention time was identical to that of authentic material. Regio-isomer was not detected by HPLC.
	Stage #1: ethyl trifluoroacetate,; para-methylacetophenone With sodium methylate In methanol; isopropyl alcohol at 50 - 55℃; for 2h; Stage #2: 4-hydrazinobenzene-1-sulfonamide hydrochloride With trifluoroacetic acid In methanol; isopropyl alcohol at 45 - 55℃; for 2.5h; Stage #3: With sodium hydroxide In methanol; water; isopropyl alcohol at 20 - 65℃; for 9h;	9 Example 9 Preparation of [CELECOXIB] by addition of diketone salt to 4-SAPH-HCI To a 250mL reactor, fitted with a mechanical stirrer and maintained under a nitrogen atmosphere, was added isopropyl alcohol (54.8g, 0.912 moles), ethyl trifluoroacetate (38. 0g, 0.267 moles) and 25% sodium methoxide in methanol (53.3g, 0.246 moles). To the agitated reactor was added [4-METHYLACETOPHENONE] (27.6g, 0.206 moles). The reaction mixture was heated to [50C] and maintained for 2 hours. To a second (1 liter) reactor was added 4-sulphamidophenyl hydrazine hydrochloride (46. 0g, 0.206 moles), isopropyl alcohol (101.3g, 1.685 moles) and trifluoroacetic acid [(11.] 7g, 0.103 moles) with stirring. The reaction mixture was heated to approximately [45C.] Upon completion of the 2-hour reaction period in the 250mL reactor, the contents was added to the second reactor over approximately 10 minutes. The reaction mixture maintained at [55C] for 30 minutes. The pH was adjusted with 50% aqueous sodium hydroxide to a pH of 5-6. The reaction mixture was heated to [65C] and water was added (95g, 5.3 moles). The pH was again adjusted with 50% aqueous sodium hydroxide to a value of 5-6. Water (90g, 5.0 moles) was added over 20 minutes while maintaining the temperature at [65C.] The reaction mixture was then cooled over 9 hours to [20C.] The reaction mixture was filtered, washed twice with 50% aqueous isopropyl alcohol and dried in a vacuum over for 16 hours to yield [CELECOXIB] (65.6g) whose HPLC retention time was identical to that of authentic celecoxib. Regio-isomer was not detected by HPLC.

	Stage #1: ethyl trifluoroacetate,; para-methylacetophenone With sodium methylate In methanol; isopropyl alcohol at 50 - 55℃; for 2h; Stage #2: 4-hydrazinobenzene-1-sulfonamide hydrochloride With trifluoroacetic acid In methanol; isopropyl alcohol at 50 - 55℃; for 2.5h; Stage #3: In methanol; water; isopropyl alcohol at 20 - 65℃; for 14h;	8 Example [8] Preparation of celecoxib with anhydrous hydrazine reactant To a 250 mL reactor which had been purged with nitrogen and which had been fitted with a mechanical stirrer and a chilled condenser was charged while stirring, isopropyl alcohol (50.75g), ethyltrifluoroacetate (37.95g), sodium methoxide (25% in methanol, 53.28g) and [4'-METHYLACETOPHENONE] (27.43g). The reaction mixture was heated to [50-55C] and held for at least 2 hours. To a separate 1 L reactor which had been purged with nitrogen and fitted with a mechanical stirrer and a chilled condenser, was charged [4-SAPH HCI] (45.96g), isopropyl alcohol [(101.] 2g), water (74g) and [TRIFLUOROACETIC] acid (23.43g). The 4- [SAPH HCI] was heated to [50C] with agitation. At the completion of the 2 hour reaction period, the contents of the first reactor was transferred to the second reactor containing the [4-SAPH HCI] over a period of at least five minutes and the reaction mixture was then brought to [55C] and maintained at that temperature for at least 30 minutes. The pH of the reaction mixture was then adjusted to be within the range of 3 to 9 followed by the addition of water (95g). The contents were then heated to [65C] and the pH was again adjusted to be within the range of 3 to 9. Water (90g) was then added to the mixture over a time period of about 20 minutes while maintaining the temperature at about [65C.] The reaction mixture was then cooled to about [20C] over a period of 12 to 14 hours to produce celecoxib (62-65g) with less than 0.05% regio-isomer and undetectable regioisomer.
	Stage #1: ethyl trifluoroacetate,; para-methylacetophenone With sodium methylate In methanol; tert-butyl methyl ether at 45 - 55℃; Large scale; Stage #2: With hydrogenchloride In water at 55℃; for 0.5h; Large scale; Stage #3: 4-hydrazinobenzene-1-sulfonamide hydrochloride In water at 75 - 85℃; for 2h; Large scale;	1 Example 1 Preparation of celecoxib Weigh 77.0kg of methyl tert-butyl ether (MTBE) solution, 20.0kg of p-methylacetophenone solution and 27.5kg of ethyl trifluoroacetate solution in a reaction tank, and slowly dropwise add 25% of sodium methoxide under stirring and cooling Methanol solution,Maintain the reaction liquid temperature does not exceed 55 . Bi completed, 45 ~ 55 under the conditions of continued reaction 10 ~ 24h.After the reaction was completed, the solvent was distilled off under reduced pressure and then 10% hydrochloric acid solution was slowly added dropwise under stirring and cooling to maintain the temperature below 55 ° C. After completion of the dropwise addition, stirring was continued for 30 minutes, and the mixture was extracted with ethyl acetate / water. , Add activated carbon 0.4kg, stirred at room temperature for 1h and filtered.The filtrate was added 137.2kg of purified water, sulfonamido phenylhydrazine hydrochloride 33.3kg, heated to 75 ~ 85 reaction 2h, cooled to room temperature crystallization, centrifugation, and dried to give crude celecoxib.Weigh celecoxib crude 20.0kg in the reaction tank, add 60% ethanol (m / m) 80 liters, heated to 75 ~ 85 ° C and stirred for 1 ~ 2h. After cooling to room temperature crystallization, centrifugation, drying celecoxib.

Reference： [1]Current Patent Assignee: PFIZER INC - WO2003/99794, 2003, A1 Location in patent: Page 40-41
[2]Current Patent Assignee: PFIZER INC - WO2003/99794, 2003, A1 Location in patent: Page 43
[3]Current Patent Assignee: PFIZER INC - WO2003/99794, 2003, A1 Location in patent: Page 42
[4]Current Patent Assignee: PFIZER INC - WO2003/99794, 2003, A1 Location in patent: Page 41-42
[5]Current Patent Assignee: NANJING SANHOME INVESTMENT GROUP CO LTD - CN104418804, 2017, B Location in patent: Paragraph 0055; 0056; 0057

14
[ 720-94-5 ]
[ 4392-54-5 ]
[ 169590-42-5 ]

Yield	Reaction Conditions	Operation in experiment
		Into a 100 mL Morton flask fitted with a reflux condenser, a nitrogen inlet and a thermometer was weighed 67 mg 4-SAPH (free base, 0.36 [MMOL).] To the 4-SAPH was added 15 mL isopropyl alcohol followed by 5 mL of a 0.36M TFA stock solution (in isopropyl alcohol). The mixture was heated to [40C] with an oil bath giving a homogeneous solution. At [40C] a 10 ml aliquot of a 0.036M 1,1, 1- [TRIFLUORO-4- (4APOS;-METHYLPHENYL)-2,] 4-butanedione (in isopropyl alcohol) diketone stock solution, preheated to [40C,] was added all at once to the 4-SAPH mixture. Aliquots were taken periodically [(200] [UL),] quenched in 0.2M [NAOH] (in 55: 45 acetonitrile : water), and cooled in ice. Analysis was carried out by HPLC and area percent values were converted to molar concentrations using standards. The results using four different concentrations of 4-SAPH are given in table 4 below for the initial rate of [CELECOXIB] and Hydroxyregioisomer formation. The diketone concentration for all four trials was 12 mmolar.
	With hydrogenchloride; In water; at 98 - 100℃;	Stage-2:Preparation of 4-[5-(4-methylphenyl)-3-(trifluorornethyl)-lh-pyrazol-l- yljbenzenesulfonamide (Celecoxib) (I) l-(4-Methylphenyl)-4,4,4-trifluorobutane-l,3-dione (IV) (80 g, 0.348 mol), 4- hydrazinophenylsulfonamide (V) (77.74 g, 0.348 mol) and concentrated hydrochloric acid (18.6 g) were added to DM water (500 ml) and heated to 98-1000C. The mass was stirred for 4 hr to complete the reaction. The reaction mass was cooled to 70-75 C and a mixture of toluene (600 ml) and methanol (10 ml) was added to the reaction mass. After 1 hr stirring at 70-750C, the reaction mass was cooled to 20-250C, the product was filtered and lambdavashed with toluene (100 ml) followed by DM water (200 ml). The product obtained was dried at 55-600C under reduced pressure to produce 1 15 g of Celecoxib crude. Chromatographic purity: 99percent(by PTPLC, by area normalization)

Reference： [1]Patent: WO2003/99794,2003,A1 .Location in patent: Page 37-38
[2]Patent: WO2010/95024,2010,A2 .Location in patent: Page/Page column 9

15
[ 169590-42-5 ]
4-(5-p-tolyl-3-(trifluoromethyl)-1H-pyrazol-1-yl)benzenesulfonyl azide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
94%	With triflic azide; sodium hydrogencarbonate; copper(II) sulfate In water; toluene; <i>tert</i>-butyl alcohol at 20℃; for 38h;

Reference： [1]Raushel, Jessica; Pitram, Suresh M.; Fokin, Valery V. [Organic Letters, 2008, vol. 10, # 16, p. 3385 - 3388]

16
[ 720-94-5 ]
[ 17852-52-7 ]
[ 331943-04-5 ]
[ 169590-42-5 ]

Reference： [1]Organic Process Research and Development,2009,vol. 13,p. 98 - 101

17
[ 685107-23-7 ]
[ 32315-10-9 ]
[ 169590-42-5 ]
[ 1369589-68-3 ]

Yield	Reaction Conditions	Operation in experiment
	Stage #1: 3,5-bis-triisopropylsilyloxymethyl phenol; bis(trichloromethyl) carbonate With pyridine In dichloromethane at -78 - 20℃; for 1h; Stage #2: 4-[5-(4-(methyl)phenyl)-3-(trifluoromethyl)-1H-pyrazol-1-yl]benzenesulphonamide With pyridine In dichloromethane at -78 - 0℃; for 1h;	7.5 3,5-Bis[(triisopropylsilyloxy)methyl]phenyl {4-[5-(4-methylphenyl)-3-(trifluoromethyl)-1H-pyrazol-1-yl]phenyl}sulfonylcarbamate To a solution of the previous phenol (product of Step 4) and TRIPHOSGENE in CH2Cl2, pyridine is added dropwise AT-78°C. After 1h of stirring at rt, the final suspension is transferred via a canula to a solution Celebrex and pyridine mL CH2Cl2 cooled AT-78°C. After 1 h at 0°C, the reaction mixture is poured into a separatory funnel containing ETOAC/NH4Cl (sat). The phases were separated and the aqueous phase is extracted twice with EtOAc. The organic layers are combined, washed with brine, dried over anhydrous Na2SO4 and evaporated to dryness. The crude material is further purified by flash chromatography eluting with EtOAc/hexanes to yield the title compound.

Reference： [1]Current Patent Assignee: MERCK & CO INC - WO2004/37798, 2004, A1 Location in patent: Page 35

18
[ 190442-16-1 ]
[ 32315-10-9 ]
[ 169590-42-5 ]
[ 685106-98-3 ]

Yield	Reaction Conditions	Operation in experiment
	Stage #1: 3-hydroxy-α-nitrate-benzenemethanol; bis(trichloromethyl) carbonate With pyridine In dichloromethane at -78 - 20℃; for 1h; Stage #2: 4-[5-(4-(methyl)phenyl)-3-(trifluoromethyl)-1H-pyrazol-1-yl]benzenesulphonamide With pyridine In dichloromethane at -78 - 0℃; for 1h;	1 4-[(Nitrooxy)methyl]phenyl {4-[5-(4-methylphenyl)-3-(trifluoromethyl)-1H-pyrazol-1-yl]phenyl}sulfonylcarbamate To a solution OF 3-NITROOXYMETHYLPHENOL (1.69 g, 10 mmol) and triphosgene (0.92 g, 3.1 mmol) in 100 ml of CH2C12, pyridine (0.86 g, 11 mmol) is added dropwise AT-78 °C. After 1h of stirring at rt, the final suspension is transferred via a canula to a solution of Celebrex (3. 81 g, 10 mmol) and pyridine 0.86g in CH2C12 cooled AT-78 °C. After 1 h at 0 °C, the reaction mixture is poured into a separatory funnel containing EtOAc (50 ML)/NH4C1 (50 mL, sat). The phases are separated and the aqueous phase is extracted twice with EtOAc (2 * 50 mL). The organic layers are combined, washed with brine, dried over anhydrous NA2S04 and evaporated to dryness. The crude material can be further purified by flash chromatography eluting with 1: 3 EtOAc/hexanes to yield the title compound.

Reference： [1]Current Patent Assignee: MERCK & CO INC - WO2004/37798, 2004, A1 Location in patent: Page 29-30

19
[ 1094772-24-3 ]
[ 169590-42-5 ]
[ 1233497-36-3 ]

Yield	Reaction Conditions	Operation in experiment
70%	Stage #1: 5-[2-(2-carboxyethyl)phenylazo]-2-hydroxybenzoic acid tert-butyl ester; 4-[5-(4-(methyl)phenyl)-3-(trifluoromethyl)-1H-pyrazol-1-yl]benzenesulphonamide With dmap; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride In 1,2-dichloro-ethane; <i>tert</i>-butyl alcohol at 20℃; for 24h; Stage #2: In ethyl acetate; 1,2-dichloro-ethane; <i>tert</i>-butyl alcohol for 2h;	1 Tert-Butyl ester of Celecoxib Azocarrier Prodrug; Into a round bottom flask was added the azo carrier (0.35 mmol, 0.13 g), t-BuOH (4.5 ml), ClCH2CH2Cl (4.5 ml), DMAP (3 eq., 1.05 mmol, 0.13 g), P- EDC (1.69 g) and Celecoxib (0.7 eq., 0.25 mmol, 0.09 g). The resulting mixture was allowed to stir at room temperature for 24 hours. The reaction mixture was then diluted with EtOAc (4 ml), and Amberlyst-15 (2.6 g) was added to the reaction and the reaction was left stirring for additional two hours. At this time the reaction was filtered through a short plug of silica gel and the residue was rinsed with additional EtOAc. The resulting filtrate was concentrated to afford the product as orange oil (0.16 g). The crude mixture was columned using methylene chloride:EtOAc (9:1) as a mobile phase to yield the product as orange oil (70%).IRVBrø*(KBr): 3071.79, 1722.97, 1672.76, 1594 cm"1. 1H-NMR (CDCl3) δ: 11.51 (IH, s), 8.42 (IH, d, J2.48 Hz), 7.98 (IH, dd, J 9.04 and 2.52 Hz), 7.93 (2H, d, J9.04 Hz), 7.65 (IH, m), 7.46 (2H, d, J 8.52 Hz), 7.32 (IH, m), 7.20 (3H, m), 7.09 (4H, m), 6.76 (IH, s), 3.37 (2H, t, J 7.52 Hz), 2.69 (2H, t, J 7 Hz), 2.40 (3H5 s), 1.68 (9H, s).13C-NMR (CDCl3) δ: 169.01 (C, C=O, C-16), 164.04 (C, C-13), 149.40 (C, C-5), 144.86 (C, C-27), 144.82 (C, C-10), 143.99 (C, C-25), 143.60 ( C, C- 35), 142.99 (C, C-22), 139.44 (C, C-4), 137.91 (C, C-19), 137.14 (C, C-28), 130.71 (C, C-28), 130.04 (CH, C-9), 129.39 (CH, C-21), 129.02 (CH, C-23), 128.98 (CH, C-30, C-32), 128.65 ( CH, C-Il), 128.25 (CH, C-7), 127.32 (CH, C-29, C-33), 126.21 (CH, C-15), 125.19 (C, C-31), 124.58 (CH, C-20, C-24), 118.23 (CH, C-14), 115.45 (CH, C-6), 113.46 (C, C-12), 106.07 (CH, C-26), 83.39 (C, C-17), 38.01 (CH2, C-2), 27.75 (CH3, C-18), 25.72 (CH2, C-3), 20.89 (CH3, C-34).
	With dmap In dichloromethane; <i>tert</i>-butyl alcohol

Reference： [1]Current Patent Assignee: UNIVERSITY OF DUBLIN - WO2010/72734, 2010, A2 Location in patent: Page/Page column 27-29
[2]Location in patent: scheme or table Marquez Ruiz, Juan F.; Kedziora, Kinga; Keogh, Brian; Maguire, Jacqueline; Reilly, Mary; Windle, Henry; Kelleher, Dermot P.; Gilmer, John F. [Bioorganic and Medicinal Chemistry Letters, 2011, vol. 21, # 22, p. 6636 - 6640]

20
[ 1233497-42-1 ]
[ 169590-42-5 ]
[ 1233497-37-4 ]

Yield	Reaction Conditions	Operation in experiment
46.4%	Stage #1: C₂₀H₂₂N₂O₄; 4-[5-(4-(methyl)phenyl)-3-(trifluoromethyl)-1H-pyrazol-1-yl]benzenesulphonamide With dmap; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride In 1,2-dichloro-ethane at 20℃; for 24h; Stage #2: In ethyl acetate; 1,2-dichloro-ethane for 2h;	2 Experimental procedure (E)-tert-butyl 4-((2-(3-oxo-3-(2-(p-tolyl)-4-trifluoromethyl)cyclopenta-2,4-dien-l-yl)phenylsuIfonamido)propyl)phenyl)diazenyl)benzoate; Into a round bottom flask was added the azo carrier (0.21 mmol, 0.076 g), t-BuOH (3 ml), ClCH2CH2Cl (3 ml), DMAP (3 eq, 0.64 mmol, 0.078 g), P-EDC (1.03 g) and the celecoxib (0.7 eq, 0.15 mmol, 0.06 g). The resulting mixture was allowed to stir at room temperature for 24 hours. The reaction mixture was then diluted with EtOAc (4 ml), and Amberlyst-15 (1.58 g) was added to the reaction and the reaction was left stirring for additional two hours. At this time the reaction was filtered through a short plug of silica gel and the residue was rinsed with additional EtOAc. The resulting filtrate was concentrated to afford the product as orange oil (O.lg). The crude mixture was columned using DCM: EtOAc (9: 1) to yield the product as orange oil (0.07 g, 46.4 %). 1H-NMR (CDCl3) δ: 8.13 (d, 2H, J 8.24 Hz), 7.95 (d, 2H, J 8.56 Hz), 7.87 (d, 2H, J 8.52 Hz), 7.68 (d, IH, J 7.52 Hz), 7.44 (d, 2H, J 8.04 Hz), 7.34 (t, 2H, J 8.04 Hz), 7.27 (t, 2H, J 7.28 Hz), 7.18 (d, 2H, J 7.28 Hz), 7.12 (d, 2H, J 8.04 Hz), 6.76 (s, IH), 3.41 (t, 2H, J 7.28 Hz), 2.70 (t, 2H, J 7.52 Hz), 2.38 (s, 3H), 1.63 (s, 9H). 13C-NMR (CDCl3) δ: 165.90, 165.13,154.85, 149.85, 145.30, 144.76, 143.58, 142.39, 139.86 , 137.89, 137.27, 132.17, 130.63, 130.52, 129.81, 129.34, 128.77, 128.65, 128.35, 127.65, 125.65, 125.05, 122.63, 118.23, 115.72, 113.73, 106.50, 81.62, 38.56, 28.11, 26.36, 21.34.

Reference： [1]Current Patent Assignee: UNIVERSITY OF DUBLIN - WO2010/72734, 2010, A2 Location in patent: Page/Page column 32-33

21
[ 1070955-54-2 ]
[ 169590-42-5 ]
[ 1233497-38-5 ]

Yield	Reaction Conditions	Operation in experiment
60%	Stage #1: C₁₄H₁₉NO₄; 4-[5-(4-(methyl)phenyl)-3-(trifluoromethyl)-1H-pyrazol-1-yl]benzenesulphonamide With dmap; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride In 1,2-dichloro-ethane; <i>tert</i>-butyl alcohol Stage #2: In ethyl acetate; 1,2-dichloro-ethane; <i>tert</i>-butyl alcohol for 2h;	(2-{3-Oxo-3[4-5(-p-tolyl-3-trifluoromethyl-pyrazol-l-yl)- benzenesulfonylamino]-propyl}-phcnyl)-carbaniic acid tert-butyl ester; Into a round bottom flask was BOC-amino phenyl propionic acid (0.78 mmol, 0.2 g), /-BuOH (9 mL), ClCH2CH2Cl (9 mL), DMAP (3 eq, 2.34 mmol, 0.27 g), P-EDC (3.6 g) and the Celecoxib (0.7 eq, 0.54 mmol, 0.21 g). The reaction mixture was then diluted with EtOAc (4 ml), and Amberlyst-15 (4.8 g) was added to the reaction and the reaction was left stirring for additional two hours. At this time the reaction was filtered through a short plug of silica gel and the residue was rinsed with additional EtOAc. The resulting filtrate was concentrated to afford the product as colourless oil (0.26 g). The crude mixture was columned using Hexane: EtOAc (7: 3) as a mobile phase to yield the product as white off crystals (0.19g, 60 %) m.p 184-186 °C. IRVTOα(KBr): 3437.21, 1564.30, 1415.85, 1261.62 cm"1. 1H-NMR (MeOD) δ: 9.48 (s, IH, NH), 7.89 (d, 2H, J 8.52 Hz), 7.45 (d, 2H J9.04 Hz), 7.37 (d, IH, J 7.56 Hz), 7.21 (d, 3H J 8.04 Hz), 7.14 (d, 2H, J8.04 Hz), 6.96 (t, IH, J7.52 Hz), 6.92 (d, IH, J6.52 Hz), 6.5 (s, IH, NH), 2.84 (t, 2H, J 7 Hz), 2.48 (t, 2H J 7.04 Hz), 2.40 (s, 3H), 1.53 (s, 9H). 13C-NMR (MeOD) δ: 178.64 (C, C=O, C-I), 155.13 (C=O, C-IO), 145.48 (C, C-21), 143.87 (C, C-19), 141.05 (C, C-16), 139.44 (C, C-25), 135.59 (C, C- 13), 134.96 (C, C-5), 132.19 (C, C-4), 131.01 (C, C-22), 129.22 (CH, C-26, C- 24), 129.19 (CH, C-23, C-27), 128.62 (CH, C- 14, C- 18), 127.80 (CH, C-7, C-9), 125.98 (CH, C-8), 124.89 (C, C-29), 124.82 (CH, C-6), 124.65 (CH,C-17, C-15), 105.29 (CH, C-20), 79.46 (C, C-I l), 39.44 (CH2, C-3), 27.34 (CH3, C-12), 26.60 (CH2, C-3), 22.34 (CH3, C-28). HRMS: Expected (M-Na+) = 651.1875, Found (M-Na+) = 651.11865.
	With dmap In dichloromethane; <i>tert</i>-butyl alcohol

Reference： [1]Current Patent Assignee: UNIVERSITY OF DUBLIN - WO2010/72734, 2010, A2 Location in patent: Page/Page column 35-36
[2]Location in patent: scheme or table Marquez Ruiz, Juan F.; Kedziora, Kinga; Keogh, Brian; Maguire, Jacqueline; Reilly, Mary; Windle, Henry; Kelleher, Dermot P.; Gilmer, John F. [Bioorganic and Medicinal Chemistry Letters, 2011, vol. 21, # 22, p. 6636 - 6640]

22
[ 720-94-5 ]
[ 613660-87-0 ]
[ 331943-04-5 ]
[ 169590-42-5 ]

Reference： [1]Tetrahedron Letters,2010,vol. 51,p. 5005 - 5008

23
[ 169590-42-5 ]
[ 147-85-3 ]
4-[5-(4-methylphenyl)-3-(trifluoromethyl)pyrazol-1-yl]benzenesulfonamide L-proline [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
94%	In dichloromethane	A Example: Celecoxib - L-proline co-crystal (1:2) Process A (preparation by slurrying): To a 10 mL flask equipped with magnetic stirrer containing celecoxib (509 mg, 1.34 mmol) and L-proline (307 mg, 2.68 mmol, 2 eq), was added 4 mL dichloromethane. The resultant suspension was stirred overnight. The solid was filtered with a sintered funnel (porosity 3) and washed with 1 mL cold dichloromethane. Traces of solvent were removed in vacuo at room temperature affording co-crystal celecoxib - L-proline (1:2) as a white powder (768 mg, 94%).

Reference： [1]Current Patent Assignee: Corporacion Quimico Farmaceutica Esteve SA - EP2325172, 2011, A1 Location in patent: Page/Page column 8

24
[ 853793-24-5 ]
[ 169590-42-5 ]

Yield	Reaction Conditions	Operation in experiment
99%	With sulfuric acid at 20℃; for 8h;	General procedure: To a 5mL round bottom flask were added 4c or 4d(0.1mmol), concentrated H2SO4 (1mL). The reaction was stirred at room temperature for 8h, and then was added to water (10mL) carefully. The mixture was extracted with Et2O. The organic layer was dried over Na2SO4, filtered, and then concentrated in vacuo. The residue was purified by column chromatography on silica gel (DCM/EtOAc=10/1) to afford Celecoxib or Mavacoxib (99% yield) as a white solid. The analytical data are in accordance with literature.9,16,17
70%	With sulfuric acid at 20℃; for 4h;
69%	With sulfuric acid at 20℃; for 2h;	Celecoxib (1) N,N-Dibenzyl-4-[5-(4-methylphenyl)-3-(trifluoromethyl)-1H-pyrazol-1-yl]benzenesulfonamide (10) (0.34 g, 0.606 mmol) was added portion wise to cH2SO4 (5 mL). The reaction was stirred at room temperature for 2 h. The mixture was then added carefully to cold H2O (30 mL) before extracting with TBME (2 × 15 mL). The organic layers were combined then washed with an aqueous solution of saturated NaHCO3 (20 mL). The organic layer was collected, dried over Na2SO4, filtered, and then concentrated in vacuo. The residue was purified using chromatography on silica gel (via ISCO) eluting with EtOAc in heptane (0-30%). The solid obtained was finally recrystallized from heptane to afford a white solid. Yield = 0.160 g (69%).CommentSpectroscopic details are consistent with those reported.refPreviewPlaceHolder2bCommentHPLC: Rt = 1.70 min, purity >95% by ELSD detection.CommentLRMS: m/z 382 [M + H]+.Comment1H NMR (400 MHz; CDCl3): δ 2.38 (s, 3H), 4.99 (br s, 2H), 6.74 (s, 1H), 7.11 (d, 2H, J = 8.20 Hz), 7.18 (d, 2H, J = 8.01 Hz), 7.47 (d, 2H, J = 8.59 Hz), 7.90 (d, 2H, J = 8.59 Hz).Comment13C NMR (100 MHz; CDCl3): 21.5, 106.6, 119.9, 125.7, 125.9, 127.7, 129.0, 130.0, 140.0, 141.6, 142.8, 145.5.CommentAnal. Calcd for C17H14F3N3O2S: C, 53.54; H, 3.70; N 11.02. Found: C, 53.79; H, 3.65; N, 10.84.

Reference： [1]Wang, Yongdong; Han, Jing; Chen, Jie; Cao, Weiguo [Tetrahedron, 2015, vol. 71, # 43, p. 8256 - 8262]
[2]Li, Feng; Nie, Jing; Sun, Long; Zheng, Yan; Ma, Jun-An [Angewandte Chemie - International Edition, 2013, vol. 52, # 24, p. 6255 - 6258]
[3]Location in patent: experimental part Gaulier, Steven M.; McKay, Reuben; Swain, Nigel A. [Tetrahedron Letters, 2011, vol. 52, # 45, p. 6000 - 6002]

25
C₁₇H₁₆F₃N₃O₂S [ No CAS ]
[ 169590-42-5 ]

Yield	Reaction Conditions	Operation in experiment
83%	With sodium anthraquinone-2-sulfonate; palladium diacetate; potassium carbonate In chlorobenzene at 110℃; for 12h;	Typical procedure for Pd-catalyzed oxidative reactions General procedure: 1a (0.5 mmol), Pd(OAc)2 (5 mol%), AMS (20 mol%), K2CO3 (0.4 equiv.), and dry chlorobenzene (1 mL) were added in a test tube. The reaction mixture was allowed to stir vigorously at 110 °C for 6 h. After cooling at room temperature, the mixture was concentrated and the residue was purified by column chromatography on Al2O3 (mobile phase: dichloromethane/methanol or petroleum ether/ethyl acetate) to afford the pure product.
77%	With [RhCl₂(p-cymene)]2; oxygen In dimethyl sulfoxide at 110℃; for 10h; Inert atmosphere;

Reference： [1]Zhu, Ye-Fu; Wei, Bo-Le; Wei, Jiao-Jiao; Wang, Wen-Qiong; Song, Wei-Bin; Xuan, Li-Jiang [Tetrahedron Letters, 2019, vol. 60, # 17, p. 1202 - 1205]
[2]Hu, Jiantao; Chen, Shi; Sun, Yonghui; Yang, Jing; Rao, Yu [Organic Letters, 2012, vol. 14, # 19, p. 5030 - 5033,4]

26
[ 2001-32-3 ]
[ 169590-42-5 ]
[ 1426535-45-6 ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2013,vol. 23,p. 1693 - 1698

27
[ 108-30-5 ]
[ 169590-42-5 ]
[ 586412-28-4 ]

Yield	Reaction Conditions	Operation in experiment
80%	Stage #1: N-[4-[5-(4-methylphenyl)-3-(trifluoromethyl)-1H-pyrazol-1yl]phenylsulfonyl]benzensulfonamide With 4-dimethylaminopyridine; triethylamine In tetrahydrofuran Inert atmosphere; Stage #2: succinic acid anhydride In tetrahydrofuran at 20℃; for 24h; Reflux;	2 Synthesis of celecoxib-sussinamidic acid pro-drug (C-SA) Synthesis of celecoxib-sussinamidic acid pro-drug (C-SA) [0100] Celecoxib (2.62 mmoles) was dissolved in anhydrous THF under argon atmosphere. DMAP and TEA (3.15 mmoles each) were added while stirring. After 5- 10 minutes, succinic anhydride (3.15 mmole) was added and reaction mixture was stirred overnight (16-18 h) at room temperature after which it was refluxed for 5-6 h (Figure 8). At the end of 24 h, when there was no further increase in the intensity of the TLC spot for the product and the reaction was stopped. The organic layer was collected and concentrated to a viscous material on rotary evaporator. The viscous material was dissolved in minimum volume of dichloromethane and washed once with equal volume of water. Final product in the organic layer was purified by column chromatography. Silica gel 60 (Geduran, particle size 40-63 μιη, EMD Chemicals) and dichloromethane/methanol were used as stationary phase and mobile phase respectively.
31%	With pyridine In toluene Reflux;	(Z)-4-Oxo-4-(4-(5-(p-tolyl)-3-(trifluoromethyl)-lH-pyrazol-l- yl)phenylsulfonamido)butanoic acid (C05) C02 (250 mg, 0.66 mmol) was dissolved in 1 mL toluene. Succinic anhydride (329 mg, 3.28 mmol) and pyridine (80 ul, 0.99 mmol) were added and refluxed overnight. The rxn was washed with NH4C1 solution, dried over magnesium sulfate and evaporated. The product was chromato graphed using 50% ethyl acetate/hexanes to yield a colorless oil (100 mg, 31% yield). 1H NMR (400 MHz, CDC13) δ 7.93-7,89 (m, 2H), 7.48-7.42 (m, 2H), 7.20-7.07 (m, 4H), 6.79 (s, 1H), 2.73-2.68 (m, 2H), 2.58-2.52 (m, 2H), 2.39 (s, 3H). LC tr=4.35 minutes (C-18 column, 5 to 95% acetonitrile/water over 6 minutes at 1.7 mL/min with detection 254 nm, at 23° C). ES(neg)MS m/z 480 (M-H calcd for C2iH18F3N305S requires 480).
	With triethylamine In acetonitrile

Reference： [1]Current Patent Assignee: UNIVERSITY OF COLORADO (SYSTEM) - WO2013/74988, 2013, A1 Location in patent: Paragraph 0021; 0100
[2]Current Patent Assignee: EUCLISES PHARMACEUTICALS - WO2014/12074, 2014, A2 Location in patent: Paragraph 00282; 00283
[3]Markowicz, Joanna; Uram, Łukasz; Wałajtys-Rode, Elżbieta; Wołowiec, Stanisław; Wróbel, Konrad [Cancers, 2022, vol. 14, # 3]

28
[ 693-11-8 ]
[ 169590-42-5 ]
[ 1448300-85-3 ]

Yield	Reaction Conditions	Operation in experiment
39%	Stage #1: 4-dimethylamino-butyric acid With O-(1H-benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate; N-ethyl-N,N-diisopropylamine In N,N-dimethyl-formamide at 20℃; for 1h; Inert atmosphere; Stage #2: 4-[5-(4-(methyl)phenyl)-3-(trifluoromethyl)-1H-pyrazol-1-yl]benzenesulphonamide In N,N-dimethyl-formamide at 20℃; for 15h;	1 Synthesis of 4-(dimethylamino)-N-((4-(5-(p-tolyl)-3-(trifluoromethyl)-1H-pyrazol-1-yl)phenyl)sulfonyl)butanamide (CXB-OCT) 30.0 mg (0.18 mmol) of 4-(dimethylamino)butanoic acid, 101.0 mg (0.27 mmol) of HBTU (O-Benzotriazole-N,N,N′,N′-tetramethyl-uronium-hexafluoro-phosphate), and 52.0 μl (0.30 mmol) of DIEA (N,N-Diisopropylethylamine) were dissolved in anhydrous 3.0 ml DMF (dimethyl formamide). The reaction was stirred for 1 hour at room temperature under argon. After 1 hour Celecoxib (0.2 mmol) was added to the reaction and the resulting reaction was stirred for 15 hours at room temperature. At the end of the reaction, the solvent was evaporated and the product was purified by flash column chromatography. Yield of the product was 39%.

Reference： [1]Current Patent Assignee: UNIVERSITY OF COLORADO (SYSTEM) - US2013/190324, 2013, A1 Location in patent: Paragraph 0125; 0126

29
[ 2483-46-7 ]
[ 169590-42-5 ]
C₃₃H₄₂F₃N₅O₇S [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
50%		Step 1: [0119] 84.0 mg (0.17 mmol) of <strong>[2483-46-7]2,6-bis((tert-butoxycarbonyl)amino)hexanoic acid</strong>, 120.0 mg (0.31 mmol) of HBTU (O-Benzotriazole-N,N,N?,N?-tetramethyl-uronium-hexafluoro-phosphate), and 75.0 mul (0.30 mmol) of DIEA (N,N-Diisopropylethylamine) were dissolved in anhydrous 3.0 ml DMF (dimethyl formamide). The reaction was stirred for 1 hour at room temperature under inert gas (argon). After 1 hour 95.0 mg of celecoxib (0.25 mmol) was added to the reaction under argon and the resulting reaction were stirred for 15 hours at room temperature. At the end of the reaction, the solvent was evaporated and the product was purified by flash column chromatography. Yield of the product was 50%.

Reference： [1]Patent: US2013/190324,2013,A1 .Location in patent: Paragraph 0117; 0118; 0119

30
[ 108-55-4 ]
[ 169590-42-5 ]
[ 1448300-84-2 ]

Yield	Reaction Conditions	Operation in experiment
89%	With N-ethyl-N,N-diisopropylamine In N,N-dimethyl-formamide at 20℃; for 15h;	1 Synthesis of 5-oxo-5-(4-(5-(p-tolyl)-3-(trifluoromethyl)-1H-pyrazol-1-yl)phenylsulfonamido)pentanoic acid (CXB-MCT) 100 mg (0.26 mmol) of Celecoxib, 114.0 mg of glutaric anhydride (0.33 mmol), and 68 μl of DIEA (N,N-Diisopropylethylamine) were dissolved in 3.0 ml of anhydrous DMF and the reaction was stirred at room temperature for 15 hours. The reaction progress was monitored by TLC. Once the reaction was completed, the solvent was evaporated under vacuum. Product was purified by flash column chromatography. Yield of the reaction was 89%

Reference： [1]Current Patent Assignee: UNIVERSITY OF COLORADO (SYSTEM) - US2013/190324, 2013, A1 Location in patent: Paragraph 0123; 0124

31
[ 13139-15-6 ]
[ 169590-42-5 ]
C₂₈H₃₃F₃N₄O₅S [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
38%	Stage #1: Boc-DL-Leu-OH With O-(1H-benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate; N-ethyl-N,N-diisopropylamine In N,N-dimethyl-formamide at 20℃; for 1h; Inert atmosphere; Stage #2: 4-[5-(4-(methyl)phenyl)-3-(trifluoromethyl)-1H-pyrazol-1-yl]benzenesulphonamide In N,N-dimethyl-formamide at 20℃; for 15h; Inert atmosphere;	1 Synthesis of 2-amino-4-methyl-N-((4-(5-p-tolyl)-3-(trifluoromethyl)-1H-pyrazol-1-yl)phenyl)sulfonyl)pentanamide [CXB-ATB (Leucine)] Step 1 [0114] 46.0 mg (0.24 mmol) of 2-((tert-butoxycarbonyl)amino)-4-methylpentanoic acid, 112.0 mg (0.3 mmol) of HBTU (O-Benzotriazole-N,N,N′,N′-tetramethyl-uronium-hexafluoro-phosphate), and 52.0 μl (0.30 mmol) of DIEA (N,N-Diisopropylethylamine) were dissolved in anhydrous 3.0 ml DMF (dimethyl formamide). The reaction was stirred for 1 hour at room temperature under inert gas (argon). After 1 hour 75.0 mg of celecoxib (0.2 mmol) was added to the reaction under argon and the resulting reaction was stirred for 15 hours at room temperature. At the end of the reaction, the solvent was evaporated and the product was purified by using flash column chromatography. Yield of the product was 38%.

Reference： [1]Current Patent Assignee: UNIVERSITY OF COLORADO (SYSTEM) - US2013/190324, 2013, A1 Location in patent: Paragraph 0112; 0113; 0114

32
(E)-5-(2,3-bis(tert-butoxycarbonyl)guanidino)-2-((tert-butoxycarbonyl)amino)pentanoic acid [ No CAS ]
[ 169590-42-5 ]
C₃₉H₅₂F₃N₇O₈S [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
50%	Stage #1: (E)-5-(2,3-bis(tert-butoxycarbonyl)guanidino)-2-((tert-butoxycarbonyl)amino)pentanoic acid With O-(1H-benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate; N-ethyl-N,N-diisopropylamine In N,N-dimethyl-formamide at 20℃; for 1h; Inert atmosphere; Stage #2: 4-[5-(4-(methyl)phenyl)-3-(trifluoromethyl)-1H-pyrazol-1-yl]benzenesulphonamide In N,N-dimethyl-formamide at 20℃; for 15h; Inert atmosphere;	1 Step 1: [0108] 84.0 mg (0.17 mmol) of (E)-5-(2,3-bis(tert-butoxycarbonyl)guanidino)-2-((tert-butoxycarbonyl)amino)pentanoic acid, 120.0 mg (0.31 mmol) of HBTU (O-Benzotriazole-N,N,N′,N′-tetramethyl-uronium-hexafluoro-phosphate), and 75.0 μl (0.30 mmol) of DIEA (N,N-Diisopropylethylamine) were dissolved in anhydrous 3.0 ml DMF (dimethyl formamide). The reaction was stirred for 1 hour at room temperature under inert gas (argon). After 1 hour 95.0 mg of celecoxib (0.25 mmol) was added to the reaction under argon and the resulting reaction were stirred for 15 hours at room temperature. At the end of the reaction, the solvent was evaporated and the residue was purified by flash column chromatography. Yield of the product was 50%.

Reference： [1]Current Patent Assignee: UNIVERSITY OF COLORADO (SYSTEM) - US2013/190324, 2013, A1 Location in patent: Paragraph 0106; 0107; 0108

33
[ 169590-42-5 ]
celecoxib sodium salt [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
100%	With sodium hydroxide In ethanol; water at 20℃; for 0.0833333h;	1 [0144] Step 1: Celecoxib was made by previously published procedures (Penning, et. al. Synthesis and Biological Evaluation of the 1,5-Diarylpyrazole Class of Cyclooxygenase-2 Inhibitors: Identification of 4-[5-(4-Methylphenyl)-3-(trifluoromethyl)-lH-pyrazol-l-yl] benzenesulfonamide (Celecoxib). J. Med. Chem. 1997, 40, 1347-1365. Celecoxib (5.0 g, 13.11 mmol) was dissolved in 120 mL ethanol, then 40 mL of water was added. Aqueous sodium hydroxide (0.49 M NaOH, 29.83 mL, 13.11 mmol) was added and stirred at room temperature for 5 minutes. The product was azeotroped with 25 mL acetonitrile and 25 mL ethanol. The resulting sodium salt of celecoxib (2a) was dried under vacuum to yield a white solid (5.32 g, quantitative yield). Comparing starting material to product by thin layer chromatography confirmed the formation of the desired sodium salt.
	With sodium hydride In tetrahydrofuran; mineral oil at 0 - 10℃; for 1h;	2.2. General Procedure for the Synthesis of Title Compounds 5 (a-1) To the solution of celecoxib (1) (0.66 mmol) in 20 mL of dry THF, 48 mg of sodium hydride (55% in paraffin oil) (2) (1.32 mmol) was added at 0-5 °C. The reaction mixture was stirred for 1 h at 0-10 °C to get the sodium salt of celecoxib intermediate (3). Various benzyl bromides/hetero halides (4a-1) (0.65 mmol) were added slowly at 0-10 °C to the intermediate 3 and then heated to 50-65 °C. The reaction mixture was stirred vigorously for 2-3 h at reflux temperature and TLC was used to check the completion of the reaction. The reaction mass was cooled to room temperature and sodium salts were removed by filtration. The solvent in filtrate was removed in a rotaevaporator to get crude title compounds (5a-1) and they were purified by column chromatography using ethyl acetate and hexane as an eluent.
	With sodium hydroxide In methanol

Reference： [1]Current Patent Assignee: EUCLISES PHARMACEUTICALS - WO2014/12000, 2014, A2 Location in patent: Paragraph 0144
[2]Madhava, Golla; Ramana, Katla V.; Sudhana, Saddala M.; Rao, Devineni S.; Kumar, Kuntrapakam H.; Lokanatha, Valluru; Rani, Asupatri U.; Raju, Chamarthi N. [Medicinal Chemistry, 2017, vol. 13, # 5, p. 484 - 497]
[3]Bansal, Arvind K.; Joshi, Prachi; Kashyap, Mahesh Chand; Mandal, Sanjay K.; Mukesh, Sumit; Sangamwar, Abhay T.; Sathe, Vasant [Molecular Pharmaceutics, 2021, vol. 18, # 6, p. 2334 - 2348]

34
[ 1538566-37-8 ]
[ 169590-42-5 ]
[ 1538558-30-3 ]

Yield	Reaction Conditions	Operation in experiment
7%	With dmap; dicyclohexyl-carbodiimide In dichloromethane at 20℃;	(Z)-3,7-Dimethyl-l,9-dioxo-l-(4-(5-(p-tolyl)-3-(trifluoromethyl)-lH-pyrazol- l-yl)phenylsulfonamido)-6,8,10-trioxa-3,4,5-triazadodec-4-ene 4-oxide (407) C02 (126 mg, 0.33 mmol) and N207 (108 mg, 0.41 mmol) were dissolved mL methylene chloride. Dicyclohexylcarbodiimide (85 mg, 0.41 mmol) and 4-dimethylamino pyridine (10 mg, 0.08 mmol) were added and stirred at room temperature overnight. The reaction underwent only partial conversion to product. The reaction mixture was evaporated and dissolved in ethyl acetate. The organic layer was washed with sat. potassium hydrogensulfate solution and brine, dried over magnesium sulfate and evaporated. The product was chromato graphed using 35% ethyl acetate/hexanes to obtain a colorless oil (15 mg, 7% yield). 1H NMR (400 MHz, CDC13) δ 8.03-8.02 (m, 2H), 7.48-7.46 (m, 2H), 7.20-7.11 (m, 4H), 6.75 (s, IH), 6.40 (dq, J=41.5, 5.6 Hz, IH), 4.29-4.19 (m, 2H), 4.04 (d, J=6.3 Hz, 2H), 3.18 (d, J=2.8 Hz, 3H), 2.86 (d, J=4.9 Hz, IH), 2.39 (s, 3H), 1.62 (dd, J=29.5, 5.6 Hz, 3H), 1.32 (tt, J=13.9, 7.2 Hz, 3H). LC tr=4.84 minutes (C-18 column, 5 to 95% acetonitrile/water over 6 minutes at 1.7 mL/min with detection 254 nm, at 23° C). ES(neg)MS m/z 627 (M-H calcd for C25H27F3N608S requires 627).

Reference： [1]Current Patent Assignee: EUCLISES PHARMACEUTICALS - WO2014/12074, 2014, A2 Location in patent: Paragraph 00267; 00268

35
[ 169590-42-5 ]
[ 639010-33-6 ]

Yield	Reaction Conditions	Operation in experiment
100%	With sodium hydroxide In ethanol; water at 20℃; for 0.0833333h;	4-(5-(p-Tolyl)-3-(trifluoromethyl)-lH-pyrazol-l-yl)benzenesulfonamide sodium salt (C04) C02 (5.0 g, 13.11 mmol) was dissolved in 120 mL ethanol, then 40 mL of water was added. Aqueous sodium hydroxide (0.49 M NaOH, 29.83 mL, 13.11 mmol) was added and stirred at room temperature for 5 minutes. The product was azeotroped with 25 mL acetonitrile and 25 mL ethanol. The resulting sodium salt of celecoxib (2) was dried under vacuum to yield a white solid (5.32 g, quantitative yield). Comparing starting material to product by thin layer chromatography confirmed the formation of the desired sodium salt.

Reference： [1]Current Patent Assignee: EUCLISES PHARMACEUTICALS - WO2014/12074, 2014, A2 Location in patent: Paragraph 00258; 00259

36
[ 102-09-0 ]
[ 1122-58-3 ]
[ 169590-42-5 ]
[ 1538566-50-5 ]

Yield	Reaction Conditions	Operation in experiment
98%	In acetonitrile at 20℃; for 0.166667h;	(Z)-4 Dimethylamino)-N-((4-(5-(p-tolyl)-3-(trifluoromethyl)-lH-pyrazol-l- yl)phenyl)sulf onyl)pyridin- 1 -ium- 1 -carbimidate ( C03) C02 (5.0 g, 13.11 mmol) was dissolved in 20 mL acetonitrile. 4-Dimethylamino pyridine (3.30 g, 27.01 mmol) was added, followed by diphenyl carbonate (2.95 g, 13.77 mmol) and stirred at room temperature for 10 minutes. The resulting white precipitate was filtered, washed with ethyl ether and dried under vacuum (6.77 g, 98% yield). 1H NMR (400 MHz, d- DMSO) δ 8.23-8.20 (m, 2H), 7.82-7.78 (m, 2H), 7.39-7.36 (m, 2H), 7.29-7.25 (m, 2H), 7.09- 7.04 (m, 1H), 6.99-6.96 (m, 2H), 6.91-6.88 (m, 2H), 3.18 (s, 6H), 2.31 (s, 3H). LC tr=4.93 minutes (C-18 column, 5 to 95% acetonitrile/water over 6 minutes at 1.7 mL/min with detection 254 nm, at 23° C). ES(pos)MS m/z 502 (M+H calcd for C25H22F3N503S requires 502), ES(neg)MS m/z 500 (M-H calcd for C25H22F3N503S requires 500).

Reference： [1]Current Patent Assignee: EUCLISES PHARMACEUTICALS - WO2014/12074, 2014, A2 Location in patent: Paragraph 00211; 00212

37
[ 169590-42-5 ]
[ 544686-20-6 ]

Yield	Reaction Conditions	Operation in experiment
	With [(COD)Ir(tribenzylphosphine₎(1,3-bis(2,4,6-trimethylphenyl)imidazolin-2-ylidene)]PF₆; deuterium In dichloromethane at 20℃; for 1h; Inert atmosphere; Sealed tube; regioselective reaction;
	With ((CH₃)2C₃N₂(C₆H₂(CH₃)3)2)Ir(C₈H₁₂)Cl; deuterium In dichloromethane at 25℃; for 2h; chemoselective reaction;
	With deuterium at 100℃; Sealed tube;

Reference： [1]Brown, Jack A.; Cochrane, Alison R.; Irvine, Stephanie; Kerr, William J.; Mondal, Bhaskar; Parkinson, John A.; Paterson, Laura C.; Reid, Marc; Tuttle, Tell; Andersson, Shalini; Nilsson, Gran N. [Advanced Synthesis and Catalysis, 2014, vol. 356, # 17, p. 3551 - 3562]
[2]Kerr, William J.; Reid, Marc; Tuttle, Tell [ACS Catalysis, 2015, vol. 5, # 1, p. 402 - 410]
[3]Valero, Mégane; Mishra, Anurag; Blass, Jennifer; Weck, Remo; Derdau, Volker [ChemistryOpen, 2019, vol. 8, # 9, p. 1183 - 1189]

38
[ 915280-82-9 ]
[ 18276-81-8 ]
[ 169590-42-5 ]

Yield	Reaction Conditions	Operation in experiment
55%	With lithium hydroxide In 1,2-dimethoxyethane at 20℃; for 10h; regioselective reaction;	Representative procedure forthe synthesis of pyrazole 5 General procedure: 1a (227 mg, 1.0 mmol) and 4a (175 mg,1.0 mmol) were dissolved in 3 mL of DME. LiOH (48 mg, 2.0 mmol) was added to the reaction mixture. The reaction mixture was stirred at rt for 10 h. HPLC indicated completion of reaction. Water (6 mL)was added to the reaction mixture, the reaction mixture was then stirred overnight. Pyrazole 5a (278 mg, 95% yield) was then filtered and dried. When pyrazole product is oil, the reaction mixture was concentrated and column chromatography using heptane and ethyl acetate gave the desired product.
55%	With lithium hydroxide In 1,2-dimethoxyethane at 20℃; for 10h; regioselective reaction;	Representative procedure forthe synthesis of pyrazole 5 General procedure: 1a (227 mg, 1.0 mmol) and 4a (175 mg,1.0 mmol) were dissolved in 3 mL of DME. LiOH (48 mg, 2.0 mmol) was added to thereaction mixture. The reaction mixture was stirred at rt for 10 h. HPLCindicated completion of reaction. Water (6 mL) was added to the reactionmixture, the reaction mixture was then stirred overnight. Pyrazole 5a (278 mg, 95% yield) was then filtered and dried. When pyrazole product is oil,the reaction mixture was concentrated and column chromatography using heptaneand ethyl acetate gave the desired product.

Reference： [1]Sun, Aixue; Ye, Jia-Hai; Yu, Haitao; Zhang, Wenchao; Wang, Xiaolong [Tetrahedron Letters, 2015, vol. 55, # 4, p. 889 - 892]
[2]Sun, Aixue; Ye, Jia-Hai; Yu, Haitao; Zhang, Wenchao; Wang, Xiaolong [Tetrahedron Letters, 2014, vol. 55, # 4, p. 889 - 892]

39
[ 720-94-5 ]
4-hydrazinobenzene-1-sulfonamide hydrochloride [ No CAS ]
[ 169590-42-5 ]

Yield	Reaction Conditions	Operation in experiment
98.8%	In ethanol; for 24h;Inert atmosphere; Reflux;	Preparation Example 1 of the embodiment will be obtained orange crude celecoxib (purity: 94.1percent) 10 .0g 30ml of ethyl acetate was added and dissolved with stirring at room temperature, was slowly added dropwise 90ml of petroleum ether. Complete addition, crystallization was stirred 1 hour, filtered and dried to give a pale yellow powder celecoxib 7.8g (purity: 99.5percent).The above recrystallization was 7.8g celecoxib and 54.6mL of methanol, 5.5mL of ethyl acetate were mixed and dissolved fully, the solution of the resulting clear liquid was added 120mL of water, stirred for 2 hours, filtered, washed with purified water, dried to give 7.7g no bonding, no separation in the preparation of compositions with other materials, do not coalesce into a block of crystalline celecoxib, 98.8percent yield, 99.5percent purity.

Reference： [1]Patent: CN103724268,2016,B .Location in patent: Paragraph 0061-0062; 0068-0070

40
C₁₄H₁₁BrF₃N₃O₆S₂ [ No CAS ]
[ 766-97-2 ]
[ 169590-42-5 ]

Yield	Reaction Conditions	Operation in experiment
	With sodium acetate; copper(II) sulfate; ascorbic acid In water; acetonitrile at 45℃; for 36h;	Implementation of specific operations Water (1.0 mL) was added to the compound (1.0 mmol) and compound II (1.0 mmol) in acetonitrile (3 mL) at room temperature, followed by the addition of 10% copper sulfate solution (0.02 mL, 0.1 mmol), 20% ascorbic acid Solution (0.02 mL, 0.2 mmol), and sodium acetate (382 mg, 4.0 mmol).The mixed solution was heated at 45 ° C for 1 hour.The reaction solution was dried under reduced pressure, and then methanol (1 mL) and aqueous ammonia (5 mL) were added, extracted with ethyl acetate, dried, and the product was separated by spin-column.

Reference： [1]Current Patent Assignee: NANJING UNIVERSITY OF CHINESE MEDICINE - CN103992273, 2016, B Location in patent: Paragraph 0007; 0008

41
tapentadol hydrochloride [ No CAS ]
[ 169590-42-5 ]
C₁₄H₂₃NO*C₁₇H₁₄F₃N₃O₂S*ClH [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
98.7%	In ethanol for 2h; Reflux;	1 Preparation of Tapentadol hydrochloride and celecoxib eutectic 2.57g tapentadol hydrochloride added into100ml round-bottomed flask, add 10ml of absolute ethanol, stirring to dissolve, then add 3.81 g celecoxib, heated to reflux, the solution was clear and transparent, refluxed for 2h, about 5 ml of ethanol was distilled off, cooled at room temperature, allowed to stand for 5h, then eutectic material precipitation , Filtered , the solid was dried in vacuo at 60~65 ° C for 6h, to give 6.3 g of tapentadol hydrochloride and celecoxib eutectic, yield 98.7%.

Reference： [1]Current Patent Assignee: ANHUI YI XIN MING PHARMACEUTICAL - CN104276960, 2016, B Location in patent: Paragraph 0037; 0038

42
[ 4813-57-4 ]
[ 169590-42-5 ]
C₃₈H₅₄F₃N₃O₄S [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With tetrabutyl ammonium fluoride; potassium carbonate In dichloromethane at 45℃; for 96h;	6 Exam le 6: Synthesis of CXB-BAE-C18 Celecoxib (CXB, 1 g), K2C03 (0.3623 g), tetrabutyl ammonium fluoride (TBAF, 0.342 g) and octadecyl acrylate (0.851 g) were weighed and added to a RBF. Anhydrous DCM (35 mL) was added and stirred. The reaction was carried out under reflux conditions at 45 °C for 96 hrs. The reaction mixture was then washed twice with NaHC03 solution to remove K2C03 and TBAF. The DCM phase was dried over MgS04 and a wax-like product was obtained after vacuum distillation. The product was characterized by LC-MS.

Reference： [1]Current Patent Assignee: TEVA PHARMACEUTICAL INDUSTRIES LTD. - WO2018/13783, 2018, A1 Location in patent: Paragraph 00208

43
[ 720-94-5 ]
4-mercaptobenzenesulfonamide hydrochloride [ No CAS ]
[ 169590-42-5 ]

Yield	Reaction Conditions	Operation in experiment
32.3%	With triethylamine; In ethanol; water; for 20h;Reflux;	Ethanol (120 mL) was separately added to the reaction flask. Pure water (30 mL), <strong>[720-94-5]4,4,4-trifluoro-1-(4-methylphenyl)butane-1,3-dione</strong> (10.0 g, 43 mmol), triethylamine (4.62 g, 46 mmol) and 4-mercaptobenzenesulfonamide hydrochloride (10.2 g, 46 mmol), mechanical stirring, heating, refluxing for 20 h, sampling, HPLC detection of impurity B content of 1.38percent (Figure 3), Stop the reaction, cool, and concentrate under reduced pressure to drynessThe 30.06 g of the crude product obtained in Example 2 was weighed, and the impurity B was separated by the SFC method under the specific conditions of chromatography. Column: Chiral PAK I.D.; column size: 0.46 cm×15 cm L; mobile phase: MeOH/CO 2 = 20/80 (V/V); wave Length: UV 254 nm; Flow rate: 2.0 ml/min; Temperature: 25° C.; Methanol solution of impurity B was obtained and concentrated under reduced pressure to give 4-[3-(4-Methylphenyl)-5-(trifluoromethyl)pyrazol-1-yl]benzenesulfonamide (Impurity B) 9.7 g, yield 32.3percent, purity99.57percent

Reference： [1]Patent: CN107759519,2018,A .Location in patent: Paragraph 0040; 0042; 0045

44
[ 616-45-5 ]
[ 169590-42-5 ]
N-(pyrrolidin-2-ylidene)-4-(5-(p-tolyl)-3-(trifluoromethyl)-1H-pyrazol-1-yl)benzenesulfonamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
86%	With diazoacetic acid ethyl ester; manganese(II) perchlorate hexahydrate In cyclohexane at 90℃; for 12h; chemoselective reaction;

Reference： [1]Chen, Jijun; Long, Wenhao; Yang, Yonggang; Wan, Xiaobing [Organic Letters, 2018, vol. 20, # 9, p. 2663 - 2666]

45
[ 3721-95-7 ]
[ 169590-42-5 ]
C₂₁H₂₀F₃N₃O₂S [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
75%	With copper(I) thiophene-2-carboxylate; (4,4'-di-tert-butyl-2,2'-dipyridyl)-bis-(5-methyl-2-(4-fluorophenyl)pyridine(-1H))-iridium(III) hexafluorophosphate; N,N,N′,N′-tetramethyl-N″-tert-butylguanidine; bathophenanthroline; iodomesitylene diacetate In 1,4-dioxane at 20℃; for 1h; Inert atmosphere; Irradiation; regioselective reaction;	Procedure for decarboxylative sp3 C-N couplings General procedure: To a 20 ml or 40 ml viale quipped with a stir bar was added photocatalyst, nitrogen nucleophile, iodomesitylene dicarboxylate, copper salt, and ligand. Dioxane was added followed by addition of the base. The solution was sonicated for 1-3 min until it became homogeneous. Next, the solution was degassed by sparging with nitrogen for 5-10 min before sealing with Parafilm. The reaction was stirred and irradiated using two 34-W blue LED lamps (3 cm away, with cooling fan to keep the reaction at room temperature) for 1 h. The reaction mixture was removed from the light, cooled to ambient temperature, diluted with water (15 ml) and ethyl acetate (25 ml), and the aqueous layer was extracted with ethyl acetate (3 × 25 ml). The combined organic layers were washed with brine, dried over Na2SO4, filtered and concentrated. The residue was purified by flash chromatography on silica gel to afford the desired decarboxylative C-N coupling product. For aniline substrates, a solution of these nitrogen nucleophiles in dioxane was used; additionally, if the iodomesitylene dicarboxylate is a liquid, its solution in dioxane was used.

Reference： [1]Liang, Yufan; Zhang, Xiaheng; MacMillan, David W. C. [Nature, 2018, vol. 559, # 7712, p. 83 - 88]

46
[ 169590-42-5 ]
[ 98-89-5 ]
C₂₃H₂₄F₃N₃O₂S [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
61%	With copper(I) thiophene-2-carboxylate; (4,4'-di-tert-butyl-2,2'-dipyridyl)-bis-(5-methyl-2-(4-fluorophenyl)pyridine(-1H))-iridium(III) hexafluorophosphate; N,N,N′,N′-tetramethyl-N″-tert-butylguanidine; bathophenanthroline; iodomesitylene diacetate In 1,4-dioxane at 20℃; for 1h; Inert atmosphere; Irradiation; regioselective reaction;	Procedure for decarboxylative sp3 C-N couplings General procedure: To a 20 ml or 40 ml viale quipped with a stir bar was added photocatalyst, nitrogen nucleophile, iodomesitylene dicarboxylate, copper salt, and ligand. Dioxane was added followed by addition of the base. The solution was sonicated for 1-3 min until it became homogeneous. Next, the solution was degassed by sparging with nitrogen for 5-10 min before sealing with Parafilm. The reaction was stirred and irradiated using two 34-W blue LED lamps (3 cm away, with cooling fan to keep the reaction at room temperature) for 1 h. The reaction mixture was removed from the light, cooled to ambient temperature, diluted with water (15 ml) and ethyl acetate (25 ml), and the aqueous layer was extracted with ethyl acetate (3 × 25 ml). The combined organic layers were washed with brine, dried over Na2SO4, filtered and concentrated. The residue was purified by flash chromatography on silica gel to afford the desired decarboxylative C-N coupling product. For aniline substrates, a solution of these nitrogen nucleophiles in dioxane was used; additionally, if the iodomesitylene dicarboxylate is a liquid, its solution in dioxane was used.

Reference： [1]Liang, Yufan; Zhang, Xiaheng; MacMillan, David W. C. [Nature, 2018, vol. 559, # 7712, p. 83 - 88]

47
[ 73152-70-2 ]
[ 169590-42-5 ]
C₃₀H₃₆F₃N₃O₂S [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
55%	With copper(I) thiophene-2-carboxylate; (4,4'-di-tert-butyl-2,2'-dipyridyl)-bis-(5-methyl-2-(4-fluorophenyl)pyridine(-1H))-iridium(III) hexafluorophosphate; N,N,N′,N′-tetramethyl-N″-tert-butylguanidine; bathophenanthroline; iodomesitylene diacetate In 1,4-dioxane at 20℃; for 1h; Inert atmosphere; Irradiation; regioselective reaction;	Procedure for decarboxylative sp3 C-N couplings General procedure: To a 20 ml or 40 ml viale quipped with a stir bar was added photocatalyst, nitrogen nucleophile, iodomesitylene dicarboxylate, copper salt, and ligand. Dioxane was added followed by addition of the base. The solution was sonicated for 1-3 min until it became homogeneous. Next, the solution was degassed by sparging with nitrogen for 5-10 min before sealing with Parafilm. The reaction was stirred and irradiated using two 34-W blue LED lamps (3 cm away, with cooling fan to keep the reaction at room temperature) for 1 h. The reaction mixture was removed from the light, cooled to ambient temperature, diluted with water (15 ml) and ethyl acetate (25 ml), and the aqueous layer was extracted with ethyl acetate (3 × 25 ml). The combined organic layers were washed with brine, dried over Na2SO4, filtered and concentrated. The residue was purified by flash chromatography on silica gel to afford the desired decarboxylative C-N coupling product. For aniline substrates, a solution of these nitrogen nucleophiles in dioxane was used; additionally, if the iodomesitylene dicarboxylate is a liquid, its solution in dioxane was used.

Reference： [1]Liang, Yufan; Zhang, Xiaheng; MacMillan, David W. C. [Nature, 2018, vol. 559, # 7712, p. 83 - 88]

48
[ 106-96-7 ]
[ 169590-42-5 ]
N-(prop-2-yn-1-yl)-4-(5-(p-tolyl)-3-(trifluoromethyl)-1H-pyrazol-1-yl)benzenesulfonamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
23.8%	Stage #1: 4-[5-(4-(methyl)phenyl)-3-(trifluoromethyl)-1H-pyrazol-1-yl]benzenesulphonamide With potassium carbonate In acetone at 20℃; for 0.5h; Inert atmosphere; Stage #2: propargyl bromide In acetone at 20℃; for 24h; Inert atmosphere;	Compound A12 General procedure: Compound A12: To the solution of (celecoxib, 1013 mg 3.0 mmol)in 20 mL of acetone, anhydrous potassium carbonate (167 mg,1.2 mmol) were added with stirring at room temperature for 0.5h.Then 3-bromopropyne (0.08 mL, 1.0 mmol) was added and stirredfor 24 h at room temperature. After filtration, the filtrate wasevaporated under reduced pressure to remove the solvent. Thecrude product was chromatographed on a silica gel (ethyl acetate:petroleum ether10:1/3:1), and 298.0 mg white solid was obtained.Yield:23.8%.1H NMR (400 MHz, Chloroform-d) δ 7.81 (d,J = 8.7 Hz, 2H), 7.41 (dd, J = 8.9, 2.2 Hz, 2H), 7.19 (s, 1H), 7.11 (s, 2H),7.03 (d, J = 8.2 Hz, 2H), 6.67 (s, 1H), 3.80 (dd, J = 6.1, 2.6 Hz, 2H), 2.31(s, 3H), 2.02 (t, J = 2.5 Hz, 1H).ESI-HRMS (m/z): calcd. forC20H16F3N3NaO2S [MNa]:442.0813; found 442.0820.

Reference： [1]Li, Jili; Zhang, Jinlong; Zhang, Qiuping; Bai, Zhongjie; Zhao, Quanyi; Wang, Zhen; Chen, Yonglin; Liu, Bin [Journal of Organometallic Chemistry, 2018, vol. 874, p. 49 - 62]

49
[ 4023-79-4 ]
4-hydrazinobenzene-1-sulfonamide hydrochloride [ No CAS ]
[ 169590-42-5 ]

Yield	Reaction Conditions	Operation in experiment
95.2%	With hydrogenchloride In methanol; water at 65℃; for 3.5h;	1.2; 1.3 2) Preparation of crude celecoxib Add 500 ml of methanol to the reaction solution of the previous step.Add 50.1 g (224 mmol) of p-nonylbenzenesulfonamide hydrochloride, add concentrated hydrochloric acid (concentration: 37.5%) to adjust the pH to 3.4, and raise the temperature to 65 °C.Insulation reaction for 3.5 hours;After completion of the reaction, 530 ml of purified water was added, and the temperature was lowered to 20 ° C. After the incubation for 1.5 hours, the mixture was crystallized and suction filtered. 77.65 g of crude celecoxib was obtained with a purity of 99.5% and a yield of 90.9%.3) Preparation of celecoxib finished productAdd 40.0g (105mmol) of celecoxib to a 1000ml three-necked flask, add 250ml of methanol, stir to warm to 60 ° C to dissolve, dissolve the solution, add 1g of activated carbon to decolorize, filter; add 300ml to another three-necked bottle of purification Water, the temperature is raised to 40-50 ° C, the decolorized material droplets are added to the water, the dropping process temperature is 43.5 ° C, the temperature is lowered to 25.6 ° C crystallization, after 1.5 hours of heat preservation, suction filtration, to obtain celecoxib The cloth was 38.1 g, the purity was 99.96%, and the yield was 95.2%.

Reference： [1]Current Patent Assignee: QILU PHARMACEUTICAL GROUP CO LTD - CN108558759, 2018, A Location in patent: Paragraph 0031; 0034; 0035; 0036; 0037; 0038; 0043; 0045

50
[ 111409-79-1 ]
[ 169590-42-5 ]
4-[5-(4-methylphenyl)-3-(trifluoromethyl)-1H-pyrazol-1-yl]-2-{2-[tris(propan-2-yl)silyl]ethynyl}benzene-1-sulfonamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
63%	With cesium acetate In 1,2-dichloro-ethane at 110℃; for 24h; Inert atmosphere; Schlenk technique;	4 Example 4 4-(5-Tolyl-3-trifluoromethylmonohydropyrazolyl)-2-((triisopropylsilyl)acetylene)benzenesulfonamide (3d) Under a nitrogen atmosphere,Sulfonamide compound 1d (38.1 mg, 0.10 mmol) was sequentially added to a 15 mL Schlenk reaction tube.Alkynylation reagent 2 (20 μL, 0.15 mmol, no additional oxidant when X = Br or I; when X = H, needAgOAc(2equiv.);),Dichloro(pentamethylcyclopentadienyl) ruthenium dimer (2.3 mg, 0.0025 mmol)Or dichloro(p-methylisopropylbenzene) oxime dimer (1.5mg, 0.0025mmol),Silver bis(trifluoromethanesulfonyl)imide (4.2 mg,0.015 mmol) or silver hexafluoroantimonate (5.0 mg, 0.015 mmol), cesium acetate (30 mg, 0.36 mmol), 1,2-dichloroethane(DCE, 1 mL), and reacted at 110 ° C for 24 hours.After completion of the reaction, the mixture was cooled to room temperature, suction filtered over Celite, and evaporated. The crude product was chromatographed on a prepared silica gel plate. The selected developer or eluent was a petroleum ether to ethyl acetate in a volume ratio of 3:1.4-(5-Tolyl-3-trifluoromethylmonohydropyrazolyl)--2-((triisopropylsilyl)acetylene)benzenesulfonamide (3d),Yellow solid, yield 63% (35.3 mg).

Reference： [1]Current Patent Assignee: GUANGDONG UNIVERSITY OF TECHNOLOGY - CN108822145, 2018, A Location in patent: Paragraph 0119-0121

51
[ 1353016-70-2 ]
(3-phenyl-1,2,3-oxadiazol-3-ium-5-yl)((4-(5-(p-tolyl)-3-(trifluoromethyl)-1H-pyrazol-1-yl)phenyl)sulfonyl)amide [ No CAS ]
C₂₆H₂₁N₃O₃ [ No CAS ]
C₂₆H₂₁N₃O₃ [ No CAS ]
[ 169590-42-5 ]

Reference： [1]Chemical Communications,2018,vol. 54,p. 14089 - 14092

52
[ 169590-42-5 ]
4-(5-(4-formylphenyl)-3-(trifluoromethyl)-1H-pyrazol-1-yl)benzenesulfonamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
78%	With dipotassium peroxodisulfate; copper(ll) sulfate pentahydrate In water; acetonitrile at 65℃; for 0.75h;	1 Example 1 25 mg (0.1 mmol) of copper sulfate pentahydrate and 81.1 mg (0.3 mmol) of potassium persulfateDissolved in 2 ml of water to obtain a blue mixed solution;Then the mixed solution is heated to 65 ° C;Then, 38.1 mg (0.1 mmol) of celecoxib was dissolved in 1 ml of acetonitrile solvent and added to the mixed solution to obtain a light green solution.Heating the light green solution to condense and reflux for 45 min;Tracking the reaction through a thin layer chromatography plate with F-254 specification,After completion of the reaction, 2 ml of water and 6 ml of dichloromethane were added to the reaction mixture for extraction, and the lower layer of the extract was taken to dissolve the dichloromethane.Add anhydrous sodium sulfate to remove water, filter and take the filtrate.Finally, silica gel was added to dry dichloromethane, and the product was purified by column chromatography.The solvent was again dried and vacuumed to obtain 30.8 mg of celecoxib oxide.The yield was 78%.
56%	With dipotassium peroxodisulfate; copper(ll) sulfate pentahydrate In water; acetonitrile for 0.75h; Reflux;
45%	With dipotassium peroxodisulfate; copper(II) sulfate In water; acetonitrile at 65℃; for 1h;

35%

With dipotassium peroxodisulfate; copper(ll) sulfate pentahydrate In water; acetonitrile

Reference： [1]Current Patent Assignee: WUHAN UNIVERSITY OF TECHNOLOGY - CN108892642, 2018, A Location in patent: Paragraph 0034; 0035; 0038; 0040; 0042; 0044; 0046; 0048
[2]Li, Feng; Zhou, Yirong; Yang, Heng; Wang, Ziqi; Yu, Qinqin; Zhang, Fang-Lin [Organic Letters, 2019, vol. 21, # 10, p. 3692 - 3695]
[3]Kim, Saegun; Jeoung, Daeun; Kim, Kunyoung; Lee, Seok Beom; Lee, Suk Hun; Park, Min Seo; Ghosh, Prithwish; Mishra, Neeraj Kumar; Hong, Suckchang; Kim, In Su [European Journal of Organic Chemistry, 2020, vol. 2020, # 46, p. 7134 - 7143]
[4]Kang, Ju Young; An, Won; Kim, Suho; Kwon, Na Yeon; Jeong, Taejoo; Ghosh, Prithwish; Kim, Hyung Sik; Mishra, Neeraj Kumar; Kim, In Su [Chemical Communications, 2021, vol. 57, # 83, p. 10947 - 10950]

53
C₁₇H₁₂F₃N₄⁽¹⁺⁾*BF₄^(1-) [ No CAS ]
[ 169590-42-5 ]

Yield	Reaction Conditions	Operation in experiment
72%	With sodium metabisulfite; sodium azide; tetrabutylammomium bromide; triphenylphosphine In water; acetonitrile at 80℃; for 12h; Inert atmosphere;
72%	With sodium metabisulfite; sodium azide; tetrabutylammomium bromide; triphenylphosphine In water; acetonitrile at 80℃; for 4h; Inert atmosphere; Schlenk technique;	26 Synthesis of compound 3a: Under nitrogen protection,The diazonium salt 1ba (520.1 mg, 1.25 mmol), Na2S2O5 (190.1 mg, 1.0 mmol), NaN3 (32.5 mg, 0.5 mmol), PPh3 (157.4 mg, 0.6 mmol), TBAB (241.7 mg, 0.75 mmol) and MeCN /H2O=2/1(1 mL) was added to a Schlenk reaction tube. After the reaction was stirred at 80 ° C for 4 h,Down to room temperature, add 10mL water thinner to the systemThe mixture was extracted with ethyl acetate (10 mL*3) and dried over anhydrous sodium sulfate.Filtration, concentration and column chromatography gave a white solid 3a (72%).
	Multi-step reaction with 3 steps 1: copper dichloride; 2.9-dimethyl-1,10-phenanthroline; potassium hydrogen difluoride; 2,6-dimethylpyridine / acetonitrile / 12 h / 20 °C / Inert atmosphere; Sealed tube 2: methanesulfonic acid / water; dichloromethane / 0.33 h / 20 °C / Inert atmosphere; Sealed tube 3: sodium hydrogencarbonate; water / Inert atmosphere

Reference： [1]Wang, Ming; Fan, Qiaoling; Jiang, Xuefeng [Green Chemistry, 2018, vol. 20, # 24, p. 5469 - 5473]
[2]Current Patent Assignee: EAST CHINA NORMAL UNIVERSITY - CN109438296, 2019, A Location in patent: Paragraph 0142-0145
[3]Liu, Yongan; Pan, Qijun; Hu, Xiaojun; Guo, Yong; Chen, Qing-Yun; Liu, Chao [Organic Letters, 2021, vol. 23, # 10, p. 3975 - 3980]

54
[ 51270-89-4 ]
4-(2-(2,2,2-trifluoroethylidene)hydrazinyl)benzenesulfonamide [ No CAS ]
[ 169590-42-5 ]

Yield	Reaction Conditions	Operation in experiment
93.6%	With sodium carbonate at 60 - 70℃;	1; 2; 3 To the above reaction flask, 120 g (0.23 mol) of 20% was added dropwise.Sodium carbonate solution,Stir the temperature to 60-70 ° C,Then add 19.7 g (0.1 mol) dropwise1-(1-bromovinyl)-4-toluene,After the addition is completed,Stirring was continued for 7-8 hours, and gradually solids precipitated.TLC detection, complete conversion of raw materials, adding 100g of water to the system,Cool down to 20-30 ° C,Stir for 2h,There is a lot of solid precipitation,Filter and dry to get the crude celecoxib34.4g white solid,The yield is 90.3%, and the purity is 99.79%;In a 500mL three-necked bottle,Add 34.4 g (0.09 mol) of celecoxib crude and 150 g of 80% ethanol.After stirring and heating to 70-80 ° C to dissolve,Add activated carbon and stir for 1 hour, and filter while hot.The filtrate was transferred to another reaction flask and 130 g of water was added to precipitate a large amount of solid.Stir and warm to 80-90 ° C,Stop heating and cool down to 20-30 ° C to precipitate the product.Continue to stir for 2 hours.filter,Drying celecoxib fine 32.2g white crystalline solid,The yield is 93.6%.The purity is 99.97%.

Reference： [1]Current Patent Assignee: VALIANT CO., LTD. - CN109232422, 2019, A Location in patent: Paragraph 0030; 0032; 0033; 0034; 0036; 0037; 0038; 0040

55
[ 124-63-0 ]
[ 169590-42-5 ]
C₁₈H₁₆F₃N₃O₄S₂ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
83.1%	Stage #1: 4-[5-(4-(methyl)phenyl)-3-(trifluoromethyl)-1H-pyrazol-1-yl]benzenesulphonamide With potassium carbonate In acetonitrile Stage #2: methanesulfonyl chloride In acetonitrile at 75 - 80℃; for 8h;	1 Preparation of Compound I1 of Example 1 100 mL of a dry three-necked flask, a stirrer and a thermometer were installed, and celecoxib (95 g, 0.249 mol) and dry anhydrous acetonitrile (570 mL) and potassium carbonate (36 g, 0.26 mol) were added thereto and stirred;30 g of methanesulfonyl chloride in acetonitrile (60 mL, 0.262 mmol) was slowly added, and the mixture was heated to 75-80 ° C for 8 h, and TLC was used to identify the end of the reaction (thin layer development conditions (petroleum ether: ethyl acetate = 5:1)) After the reaction is completed, the reaction liquid is cooled and crystallized at 0 ° C to 5 ° C for 2 h, filtered, and the solid is washed with an appropriate amount of acetonitrile, and dried under vacuum at 65 ° C to 70 ° C for 6 h to obtain 95 g of pale yellow crystalline powdery solid, yield 83.1%. The HPLC content was 98.9%. Table 1 is an elemental analysis of Compound I1.

Reference： [1]Current Patent Assignee: ANHUI HEAL STAR PHARMACEUTICAL - CN110105283, 2019, A Location in patent: Paragraph 0021-0028

56
[ 421-50-1 ]
4-[1-(4-methylbenzoyl)hydrazino]benzenesulfonamide hydrochloride [ No CAS ]
[ 169590-42-5 ]

Yield	Reaction Conditions	Operation in experiment
98.6%	In ethanol; water at 25℃; for 4h;	1.2-14.2 (2) Preparation of celecoxib (I) Add 109 g (0.97 mol) of 1,1,1-trifluoroacetone, 1.3 L of 80% ethanol in water to a 5 L reaction flask, 330 g (0.97 mol) of 4-[1-(4-methylbenzoyl)hydrazino]benzenesulfonamide hydrochloride was added and reacted at 25 °C for 4 h. After the reaction is completed, add 980 g of 10% sodium carbonate aqueous solution, stir for 0.5 h, filter, dry. 363 g of celecoxib was obtained with a yield of 98.6%, HPLC purity 99.94%. The total yield was 95.1%.

Reference： [1]Current Patent Assignee: DISHA PHARMACEUTICAL GROUP; WEIHAI DISU PHARMACEUTICAL - CN110526868, 2019, A Location in patent: Paragraph 0025-0052

57
cis-tramadol [ No CAS ]
[ 169590-42-5 ]
(rac) tramadol HBr-celecoxib [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
22 g	Stage #1: cis-tramadol With hydrogen bromide In water; isopropyl alcohol at 25℃; Stage #2: 4-[5-(4-(methyl)phenyl)-3-(trifluoromethyl)-1H-pyrazol-1-yl]benzenesulphonamide In water; isopropyl alcohol at 10 - 65℃;	3 Example 3: The 10 g of (rac)-tramadol free base was dissolved in 10 ml of IPA at 25±5°C and was added 6.4 ml of 48% aqueous solution of HBr and stirred the reaction mass for 3-4 hrs at 25±5°C. The reaction mass was cooled to l0-l5°C. To the resulting clear solution was seeded with 10 mg of co-crystal of (rac) tramadol. HBr-celecoxib at l0-l5°C and slowly added hot solution of celecoxib (14.48 g of celecoxib dissolved in 50 ml of IPA) at 65±5°C for l0-l5min at l0-l5°C and stirred the reaction mass for 2-3 hrs. To the reaction mass was added 100 ml of heptane and continues stirring for further 1-2 hrs. The resulting reaction mass was filtered, washed with heptane and dried under vacuum for l5h at 25-30 °C. The solid obtained was identified as co-crystal of (rac) tramadol HBr-celecoxib. Yield: 22.0 g

Reference： [1]Current Patent Assignee: VIATRIS INC - WO2020/39456, 2020, A1 Location in patent: Page/Page column 7-8

58
[ 18368-76-8 ]
[ 169590-42-5 ]
N-(3-methylpyridin-2-yl)-4-(5-(p-tolyl)-3-(trifluoromethyl)-1H-pyrazol-1-yl)benzenesulfonamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
51%	With (PhPAd-DalPhos)NiCl(o-tol); sodium t-butanolate In 1,4-dioxane at 110℃; for 18h; Inert atmosphere; Sealed tube;

Reference： [1]Ferguson, Michael J.; McGuire, Ryan T.; Simon, Connor M.; Stradiotto, Mark; Yadav, Arun A. [Angewandte Chemie - International Edition, 2020, vol. 59, # 23, p. 8952 - 8956][Angew. Chem., 2020, vol. 132, # 23, p. 9037 - 9041,5]

59
[ 1073-67-2 ]
[ 169590-42-5 ]
C₂₅H₂₁ClF₃N₃O₂S [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
54%	With 1,1,2,2-tetramethyl-1,2-ethanediamino-N,N'-bis(3,5-di-tert-butylsalicylidene)-cobalt(II); tris(bipyridine)ruthenium(II) dichloride hexahydrate; 1,1,3,3-Tetramethyldisiloxane; 1-fluoro-2,4,6-trimethylpyridinium trifluoromethanesulfonate In 1,2-dichloro-ethane at 20℃;

Reference： [1]Sun, Han-Li; Wang, Jun-Jie; Yang, Fan; Ye, Wei-Ting; Zhu, Rong [ACS Catalysis, 2020, vol. 10, # 9, p. 4983 - 4989]

60
trans-cyclooctenol p-nitrobenzene [ No CAS ]
[ 169590-42-5 ]
TCO-celecoxib [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
88%	With dmap In N,N-dimethyl-formamide for 40h;	10 Example 10 General procedure for preparing TCO-celecoxib To a solution of celecoxib (141 mg, 0.37 mmol) in DMF (4 mL),TCO-PNB ester (100 mg, 0.34 mmol), DMAP (106 mg, 0.88 mmol) was added.The mixture was stirred for 40 h, diluted with ethyl acetate (100 mL),Wash with water (30 mL) and brine (30 mL),It was dried over sodium sulfate and concentrated in vacuo. The productOn silica gel, eluting with methanol (5%) in DCM,Purified by flash chromatography,The product TCO-celecoxib (162 mg, 88%) was obtained.

Reference： [1]Current Patent Assignee: STATE UNIVERSITY OF NEW YORK - JP2020/516621, 2020, A Location in patent: Paragraph 00374

61
[ 402-46-0 ]
[ 26974-15-2 ]
[ 169590-42-5 ]

Yield	Reaction Conditions	Operation in experiment
89.5%	Stage #1: 5-(4-methylbenzene)-3-(trifluoromethyl)-1H-pyrazole With potassium <i>tert</i>-butylate In N,N-dimethyl-formamide at 25℃; for 0.5h; Stage #2: 4-fluorophenylsulphonamide In N,N-dimethyl-formamide at 75℃; for 12h;	4-7 Synthesis of Celecoxib Add 5-(4-methylbenzene)-3-(trifluoromethyl)-1H-pyrazole (22.6g, 100.0mmol), 200ml N,N-Dimethylformamide into a 250mL three-neck flask while stirring.potassium tert-butoxide (13.4g, 120.0 mmol), stirred at 25°C for 30min, added 4-fluorobenzenesulfonamide (22.8g, 130.0mmol), heated to 75°C, stirred for 12h, and cooled to room temperature. Water was added and extracted with ethyl acetate. The organic phase was washed again with water, dried over anhydrous sodium sulfate, filtered, and concentrated to obtain a crude product. The crude product was recrystallized with ethyl acetate and n-hexane, filtered and dried to obtain Celecoxib (34.1 g, 89.5%).

Reference： [1]Current Patent Assignee: FUJIAN HAIXI PHARMACEUTICALS CO LTD - CN111484453, 2020, A Location in patent: Paragraph 0041-0048

62
[ 232947-12-5 ]
4-hydrazinobenzene-1-sulfonamide hydrochloride [ No CAS ]
[ 169590-42-5 ]

Yield	Reaction Conditions	Operation in experiment
95.5%	With hydrogenchloride In methanol; water at 80℃; for 6h;	1-5; 1-3 Example 1 1,1,1-Trifluoro-4-methylphenylbutenone20g as raw material in 200ml methanol and 60ml water,Add dilute hydrochloric acid to adjust the pH to 2 and 4-aminosulfonylphenylhydrazine hydrochloride 20.9g, heat to 80 degrees Celsius and react for 6 hours.When the temperature is lowered to 0, white crystals are precipitated,The celecoxib 34g was obtained by suction filtration and drying, with a yield of 95.5%.

Reference： [1]Current Patent Assignee: Nong Yongqiang - CN111217753, 2020, A Location in patent: Paragraph 0018-0025

63
[ 110-82-7 ]
[ 169590-42-5 ]
C₂₃H₂₄F₃N₃O₂S [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
94%	With di-tert-butyl peroxide; copper diacetate; 4,4'-di-tert-butyl-2,2'-bipyridine In acetonitrile at 25℃; for 12h; Inert atmosphere; Irradiation; chemoselective reaction;

Reference： [1]Donabauer, Karsten; König, Burkhard; Narobe, Rok; Yakubov, Shahboz; Zheng, Yi-Wen [ACS Catalysis, 2020, vol. 10, # 15, p. 8582 - 8589]

64
[ 287-92-3 ]
[ 169590-42-5 ]
C₂₂H₂₂F₃N₃O₂S [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
52%	With di-tert-butyl peroxide; copper diacetate; 4,4'-di-tert-butyl-2,2'-bipyridine In acetonitrile at 25℃; for 12h; Inert atmosphere; Irradiation; chemoselective reaction;

Reference： [1]Donabauer, Karsten; König, Burkhard; Narobe, Rok; Yakubov, Shahboz; Zheng, Yi-Wen [ACS Catalysis, 2020, vol. 10, # 15, p. 8582 - 8589]

65
[ 79-03-8 ]
[ 169590-42-5 ]
N-((4-(5′-(p-tolyl)-3′-(trifluoromethyl)-1H-pyrazol-1′-yl)phenyl)sulfonyl)propionamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With dmap; triethylamine In acetonitrile at 0 - 20℃;	4.2. General procedure for the synthesis of celebrex derivatives 2-9 General procedure: In a 50 mL round bottom flask, DMAP (100 mg, 0.26 mmol) wasslowly added to a stirring solution of celebrex (100 mg, 0.26 mmol) in 8mL acetonitrile at 0 C. Substituted benzoyl chlorides (0.65 mmol) used,slowly added to a reaction mixture at 0 C, followed by dropwiseaddition of triethylamine (73.4 mL, 0.52 mmol) as a base. After 20 min,ice bath was removed, and reaction mixture was stirred overnight atroom temperature. Reaction mixture was monitored through normalphase thin layer chromatography (TLC) by using n-hexanes, and ethylacetate (1:9) as solvent system. Upon complete consumption of reactants,the residual part was diluted with 5% aqueous HCl solution andextracted using dichloromethane. The organic phase was dried usinganhydrous Na2SO4, filtered, and evaporated. The desired compoundswere purified by column chromatography using a mixture of ethyl acetate,and n-hexanes (4:6). 4.3.1. N-((4-(5′ -(p-Tolyl)-3′ -(trifluoromethyl)-1H-pyrazol-1′ -yl)phenyl)sulfonyl)propionamide (2)White solid; Yield: 74%; 1H NMR: (400 MHz, CD3OD): δ 8.02 (d, 2H,J2,3/6,5 = 8.8 Hz, H-2, H-6), 7.52 (d, 2H, J3,2/5,6 = 8.4 Hz, H-3, H-5), 7.21(d, 2H, J3′′ ,2′′ /5′′ ,6′′ = 8.4 Hz, H-3′ ′ , H-5′ ′ ), 7.16 (d, 2H, J2′′ ,3′′ /6′′ ,5′′ = 8.4Hz, H-2′ ′ , H-6′ ′ ), 6.89 (s, 1H, H-4′ ), 2.34 (s, 3H, CH3), 2.27 (q, 2H, J CH2-2′ ′ ′ , CH3-3′ ′ ′ = 8.0 Hz, CH2-2′ ′ ′ ), 1.02 (t, 3H, J CH3-3′ ′ ′ , CH2-2′ ′ ′ = 8 Hz, CH3-3′ ′ ′ ); 13C NMR (DMSO-d6, 125 MHz): δ 172.4 (C), 145.3 (C), 142.3 (C),139.2 (C), 139.1 (C), 129.4 (CH), 128.74 (CH), 128.72 (CH), 126.0 (CH),125.1 (C), 122.2 (C), 120.1 (C), 106.2 (CH), 28.7 (CH2), 20.7 (CH3), 8.2(CH3); IR (KBr, cm 1) vmax: 3413 (N-H), 1726 (C- -O), 1470 (C- -C),1597 (C- -C), 1163 (S- -O), 1238 (S- -O); MS (FAB): m/z 438 (M++1).

Reference： [1]Kausar, Nabeela; Ullah, Saeed; Khan, Maria Aqeel; Zafar, Humaira; Atia-tul-Wahab; Choudhary, M. Iqbal; Yousuf, Sammer [Bioorganic Chemistry, 2021, vol. 106]

66
[ 98-88-4 ]
[ 169590-42-5 ]
N-((4-(5′-(p-tolyl)-3′-(trifluoromethyl)-1H-pyrazol-1′-yl)phenyl)sulfonyl)benzamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
57%	With dmap; triethylamine In dichloromethane; ethyl acetate; toluene at 22℃; for 21h; Sealed tube; Inert atmosphere;
49%	With dmap; triethylamine In acetonitrile at 20℃;	4.2. General procedure for the synthesis of celebrex derivatives 2-9 General procedure: In a 50 mL round bottom flask, DMAP (100 mg, 0.26 mmol) wasslowly added to a stirring solution of celebrex (100 mg, 0.26 mmol) in 8mL acetonitrile at 0 C. Substituted benzoyl chlorides (0.65 mmol) used,slowly added to a reaction mixture at 0 C, followed by dropwiseaddition of triethylamine (73.4 mL, 0.52 mmol) as a base. After 20 min,ice bath was removed, and reaction mixture was stirred overnight atroom temperature. Reaction mixture was monitored through normalphase thin layer chromatography (TLC) by using n-hexanes, and ethylacetate (1:9) as solvent system. Upon complete consumption of reactants,the residual part was diluted with 5% aqueous HCl solution andextracted using dichloromethane. The organic phase was dried usinganhydrous Na2SO4, filtered, and evaporated. The desired compoundswere purified by column chromatography using a mixture of ethyl acetate,and n-hexanes (4:6).
	With triethylamine In dichloromethane at 0 - 20℃; Schlenk technique; Inert atmosphere;

Reference： [1]Matheau-Raven, Daniel; Boulter, Elizabeth; Rogova, Tatiana; Dixon, Darren J. [Organic Letters, 2021, vol. 23, # 21, p. 8209 - 8213]
[2]Kausar, Nabeela; Ullah, Saeed; Khan, Maria Aqeel; Zafar, Humaira; Atia-tul-Wahab; Choudhary, M. Iqbal; Yousuf, Sammer [Bioorganic Chemistry, 2021, vol. 106]
[3]Chu, Man-Hei; Du, Xian; Li, Yi-Hui; Luo, Yong; Xu, Xiao-Hong; Yuan, Han; Zhen, Jing-Song [Organic Letters, 2022, vol. 24, # 3, p. 853 - 858]

67
[ 403-43-0 ]
[ 169590-42-5 ]
4′′′-fluoro-N-((4-(5′-(p-tolyl)-3′-(trifluoromethyl)-1H-pyrazol-1′-yl)phenyl)sulfonyl)benzamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
31%	With dmap; triethylamine In acetonitrile at 20℃;	4.2. General procedure for the synthesis of celebrex derivatives 2-9 General procedure: In a 50 mL round bottom flask, DMAP (100 mg, 0.26 mmol) wasslowly added to a stirring solution of celebrex (100 mg, 0.26 mmol) in 8mL acetonitrile at 0 C. Substituted benzoyl chlorides (0.65 mmol) used,slowly added to a reaction mixture at 0 C, followed by dropwiseaddition of triethylamine (73.4 mL, 0.52 mmol) as a base. After 20 min,ice bath was removed, and reaction mixture was stirred overnight atroom temperature. Reaction mixture was monitored through normalphase thin layer chromatography (TLC) by using n-hexanes, and ethylacetate (1:9) as solvent system. Upon complete consumption of reactants,the residual part was diluted with 5% aqueous HCl solution andextracted using dichloromethane. The organic phase was dried usinganhydrous Na2SO4, filtered, and evaporated. The desired compoundswere purified by column chromatography using a mixture of ethyl acetate,and n-hexanes (4:6).

Reference： [1]Kausar, Nabeela; Ullah, Saeed; Khan, Maria Aqeel; Zafar, Humaira; Atia-tul-Wahab; Choudhary, M. Iqbal; Yousuf, Sammer [Bioorganic Chemistry, 2021, vol. 106]

68
[ 122-01-0 ]
[ 169590-42-5 ]
4′′′-chloro-N-((4-(5′-(p-tolyl)-3′-(trifluoromethyl)-1H-pyrazol-1′-yl)phenyl)sulfonyl)benzamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
35%	With dmap; triethylamine In acetonitrile at 20℃;	4.2. General procedure for the synthesis of celebrex derivatives 2-9 General procedure: In a 50 mL round bottom flask, DMAP (100 mg, 0.26 mmol) wasslowly added to a stirring solution of celebrex (100 mg, 0.26 mmol) in 8mL acetonitrile at 0 C. Substituted benzoyl chlorides (0.65 mmol) used,slowly added to a reaction mixture at 0 C, followed by dropwiseaddition of triethylamine (73.4 mL, 0.52 mmol) as a base. After 20 min,ice bath was removed, and reaction mixture was stirred overnight atroom temperature. Reaction mixture was monitored through normalphase thin layer chromatography (TLC) by using n-hexanes, and ethylacetate (1:9) as solvent system. Upon complete consumption of reactants,the residual part was diluted with 5% aqueous HCl solution andextracted using dichloromethane. The organic phase was dried usinganhydrous Na2SO4, filtered, and evaporated. The desired compoundswere purified by column chromatography using a mixture of ethyl acetate,and n-hexanes (4:6).

Reference： [1]Kausar, Nabeela; Ullah, Saeed; Khan, Maria Aqeel; Zafar, Humaira; Atia-tul-Wahab; Choudhary, M. Iqbal; Yousuf, Sammer [Bioorganic Chemistry, 2021, vol. 106]

69
[ 586-75-4 ]
[ 169590-42-5 ]
4′′′-bromo-N-((4-(5′-(p-tolyl)-3′-(trifluoromethyl)-1H-pyrazol-1′-yl)phenyl)sulfonyl)benzamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
35%	With dmap; triethylamine In acetonitrile at 20℃;	4.2. General procedure for the synthesis of celebrex derivatives 2-9 General procedure: In a 50 mL round bottom flask, DMAP (100 mg, 0.26 mmol) wasslowly added to a stirring solution of celebrex (100 mg, 0.26 mmol) in 8mL acetonitrile at 0 C. Substituted benzoyl chlorides (0.65 mmol) used,slowly added to a reaction mixture at 0 C, followed by dropwiseaddition of triethylamine (73.4 mL, 0.52 mmol) as a base. After 20 min,ice bath was removed, and reaction mixture was stirred overnight atroom temperature. Reaction mixture was monitored through normalphase thin layer chromatography (TLC) by using n-hexanes, and ethylacetate (1:9) as solvent system. Upon complete consumption of reactants,the residual part was diluted with 5% aqueous HCl solution andextracted using dichloromethane. The organic phase was dried usinganhydrous Na2SO4, filtered, and evaporated. The desired compoundswere purified by column chromatography using a mixture of ethyl acetate,and n-hexanes (4:6).

Reference： [1]Kausar, Nabeela; Ullah, Saeed; Khan, Maria Aqeel; Zafar, Humaira; Atia-tul-Wahab; Choudhary, M. Iqbal; Yousuf, Sammer [Bioorganic Chemistry, 2021, vol. 106]

70
[ 169590-42-5 ]
[ 610-14-0 ]
2′′′-nitro-N-((4-(5′-(p-tolyl)-3′-(trifluoromethyl)-1H-pyrazol-1′-yl)phenyl)sulfonyl)benzamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
35%	With dmap; triethylamine In acetonitrile at 20℃;	4.2. General procedure for the synthesis of celebrex derivatives 2-9 General procedure: In a 50 mL round bottom flask, DMAP (100 mg, 0.26 mmol) wasslowly added to a stirring solution of celebrex (100 mg, 0.26 mmol) in 8mL acetonitrile at 0 C. Substituted benzoyl chlorides (0.65 mmol) used,slowly added to a reaction mixture at 0 C, followed by dropwiseaddition of triethylamine (73.4 mL, 0.52 mmol) as a base. After 20 min,ice bath was removed, and reaction mixture was stirred overnight atroom temperature. Reaction mixture was monitored through normalphase thin layer chromatography (TLC) by using n-hexanes, and ethylacetate (1:9) as solvent system. Upon complete consumption of reactants,the residual part was diluted with 5% aqueous HCl solution andextracted using dichloromethane. The organic phase was dried usinganhydrous Na2SO4, filtered, and evaporated. The desired compoundswere purified by column chromatography using a mixture of ethyl acetate,and n-hexanes (4:6).

Reference： [1]Kausar, Nabeela; Ullah, Saeed; Khan, Maria Aqeel; Zafar, Humaira; Atia-tul-Wahab; Choudhary, M. Iqbal; Yousuf, Sammer [Bioorganic Chemistry, 2021, vol. 106]

71
[ 169590-42-5 ]
[ 121-90-4 ]
3′′′-nitro-N-((4-(5′-(p-tolyl)-3′-(trifluoromethyl)-1H-pyrazol-1′-yl)phenyl)sulfonyl)benzamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
35%	With dmap; triethylamine In acetonitrile at 20℃;	4.2. General procedure for the synthesis of celebrex derivatives 2-9 General procedure: In a 50 mL round bottom flask, DMAP (100 mg, 0.26 mmol) wasslowly added to a stirring solution of celebrex (100 mg, 0.26 mmol) in 8mL acetonitrile at 0 C. Substituted benzoyl chlorides (0.65 mmol) used,slowly added to a reaction mixture at 0 C, followed by dropwiseaddition of triethylamine (73.4 mL, 0.52 mmol) as a base. After 20 min,ice bath was removed, and reaction mixture was stirred overnight atroom temperature. Reaction mixture was monitored through normalphase thin layer chromatography (TLC) by using n-hexanes, and ethylacetate (1:9) as solvent system. Upon complete consumption of reactants,the residual part was diluted with 5% aqueous HCl solution andextracted using dichloromethane. The organic phase was dried usinganhydrous Na2SO4, filtered, and evaporated. The desired compoundswere purified by column chromatography using a mixture of ethyl acetate,and n-hexanes (4:6).

Reference： [1]Kausar, Nabeela; Ullah, Saeed; Khan, Maria Aqeel; Zafar, Humaira; Atia-tul-Wahab; Choudhary, M. Iqbal; Yousuf, Sammer [Bioorganic Chemistry, 2021, vol. 106]

72
[ 169590-42-5 ]
[ 10397-30-5 ]
4′′′-methyl-3′′′-nitro-N-((4-(5′-(p-tolyl)-3′-(trifluoromethyl)-1H-pyrazol-1′-yl)phenyl)sulfonyl)benzamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
49%	With dmap; triethylamine In acetonitrile at 20℃;	4.2. General procedure for the synthesis of celebrex derivatives 2-9 General procedure: In a 50 mL round bottom flask, DMAP (100 mg, 0.26 mmol) wasslowly added to a stirring solution of celebrex (100 mg, 0.26 mmol) in 8mL acetonitrile at 0 C. Substituted benzoyl chlorides (0.65 mmol) used,slowly added to a reaction mixture at 0 C, followed by dropwiseaddition of triethylamine (73.4 mL, 0.52 mmol) as a base. After 20 min,ice bath was removed, and reaction mixture was stirred overnight atroom temperature. Reaction mixture was monitored through normalphase thin layer chromatography (TLC) by using n-hexanes, and ethylacetate (1:9) as solvent system. Upon complete consumption of reactants,the residual part was diluted with 5% aqueous HCl solution andextracted using dichloromethane. The organic phase was dried usinganhydrous Na2SO4, filtered, and evaporated. The desired compoundswere purified by column chromatography using a mixture of ethyl acetate,and n-hexanes (4:6).

Reference： [1]Kausar, Nabeela; Ullah, Saeed; Khan, Maria Aqeel; Zafar, Humaira; Atia-tul-Wahab; Choudhary, M. Iqbal; Yousuf, Sammer [Bioorganic Chemistry, 2021, vol. 106]

73
(2E)-cyclooct-2’-en-1’-yl 4-nitrophenyl carbonate [ No CAS ]
[ 169590-42-5 ]
C₂₆H₂₆F₃N₃O₄S [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
88%	With dmap In N,N-dimethyl-formamide for 40h;	A4 General Procedure for the Preparation of TCO-celecoxib . To a solution of Celecoxib (14 1 mg, 0.37 mmol) in DMF (4 mL) was added TCO-PNB ester (100 mg, 0.34 mmol), DMAP (106 mg, 0.88 mmol). The mixture was stirred for 40 h and diluted with ethyl acetate (100 mL), and washed with water (30 mL) and brine (30 mL), dried over sodium sulfate, and concentrated in vacuo. The product was purified by flash chromatography on silica gel eluting with methanol (5%) in DCM to afford the product TCO-celecoxib (162 mg, 88%). LC-MS: 534 [M+H] + [00463] NMR (300 MHz, CDCl3) d 8.01 (d, J= 8.7 Hz, 2 H), 7.60 (br, 1 H), 7.50 (d, J= 8.7 Hz, 2 H), 7.18 (d, J= 8.1 Hz, 2 H), 7.14 (d, J= 8.1 Hz, 2 H), 6.74 (s, 1 H), 5.69 (m, 1 H), 5.4 5 (d, J= 12.0 Hz, 1 H), 5.30 (s, 1 H), 2.4 4 (m, 1 H), 2.38 (s 3H), 2.03-0.76 (m, 9 H).

Reference： [1]Current Patent Assignee: TAMBO - WO2021/7160, 2021, A1 Location in patent: Paragraph 00462; 00463

74
C₅₈H₁₀₀O₁₀ [ No CAS ]
[ 169590-42-5 ]
C₇₅H₁₁₂F₃N₃O₁₁S [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
52%	With dmap; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; triethylamine In dichloromethane at 20℃; for 70h;	A Example A: Synthesis of Compound I-1 4-(Dimethylamino)pyridine (DMAP, 184 mg, 1.50 mmol), N-(3-dimethylaminopropyl)-N'- ethylcarbodiimide hydrochloride (EDC*HC1, 721 mg, 3.76 mmol), triethylamine (629 mL, 4.51 mmol) and celecoxib (688 mg, 1.80 mmol) were added to a solution of the carboxylic acid corresponding to the prodrug portion of the desired compound (1.44 g, 1.50 mmol) in CH2CI2 (40 mL) and the mixture stirred at rt for two days and 22 hours. The reaction was diluted with CH2CI2 (30 mL), silica gel was added and the mixture concentrated under reduced pressure. Purification by silica gel chromatography (35% to 100% ethyl acetate/hexanes) gave celecoxib prodrug 1-1 (1.04 g, 52%) as a colourless oil; 1 H NMR (400 MHz, CDCI3) δ 8.74 (s, 1H), 7.79 - 7.73 (m, 2H), 7.43 - 7.36 (m, 3H), 7.17 (d, J = 8.0 Hz, 2H), 7.11 (d, J= 8.2 Hz, 2H), 6.74 (s, 1H), 6.66 (d, J = 1.4 Hz, 1H), 6.54 (d, J = 1.5 Hz, 1H), 5.26 (m, 1H), 4.30 (dd,J = 11.9, 4.4 Hz, 2H), 4.15 (dd, J = 11.9, 5.6 Hz, 2H), 2.62 (t, J = 7.6 Hz, 2H), 2.38 (s, 3H), 2.35 - 2.29 (m, 8H), 2.25 (s, 3H), 2.07 (s, 3H), 1.85 - 1.74 (m, 2H), 1.68 - 1.58 (m, 6H), 1.56 (s, 6H), 1.46 - 1.20 (m, 56H), 0.88 (t, J = 6.8 Hz, 6H); 13C NMR (101 MHz, CDCI3) δ 176.2 (C), 173.5 (2C; C), 173.0 (C), 169.1 (C), 150.5 (C), 145.3 (C), 143.3 (C), 140.0 (C), 138.8 (C), 138.1 (C), 137.7 (C), 133.8 (CH), 131.9 (C), 129.9 (2C; CH), 129.7 (2C; CH), 128.9 (2C; CH), 125.9 (C), 124.9 (2C; CH), 123.5 (CH), 106.6 (CH), 69.1 (CH), 62.2 (2C; CH2), 49.9 (CH2), 40.5 (C), 35.4 (CH2), 34.3 (CH2), 34.2 (2C; CH2), 32.3 (2C; CH3), 32.1 (CH2), 29.85 (6C; CH2), 29.81 (4C; CH2), 29.77 (2C; CH2), 29.6 (2C; CH2), 29.5 (2C; CH2), 29.4 (2C; CH2), 29.30 (CH2), 29.27 (2C; CH2), 29.22 (CH2), 29.19 (CH2), 29.13 (CH2), 25.6 (CH3), 25.0 (2C; CH2), 24.9 (CH2), 24.8 (CH2), 22.8 (2C; CH2), 21.5 (CH3), 20.3 (CH3), 14.3 (2C; CH3); ESI-HRMS: calcd. for C75H113F3N3O11S [M+H+] 1320.8042 ; found 1320.8018 .

Reference： [1]Current Patent Assignee: MONASH UNIVERSITY - WO2021/51172, 2021, A1 Location in patent: Paragraph 00267

75
[ 106-96-7 ]
[ 169590-42-5 ]
C₂₃H₁₈F₃N₃O₂S [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
86%	With potassium carbonate In acetone	1 Example 1: Synthesis of intermediate product formula II Use celecoxib as the reactant to perform substitution reaction with 3-bromopropyne in an acetone solution dissolved with potassium carbonate, wherein the molar ratio of celecoxib, potassium carbonate and 3-bromopropyne is 1:2.5:2.3 , The amount of organic solvent is 200 times the number of moles of celecoxib. After the substitution reaction, the filtrate was collected by filtration, the solvent was removed under reduced pressure to obtain the crude celecoxib derivative product, and then the crude celecoxib derivative product was subjected to petroleum ether and ethyl acetate in a volume ratio of 10:1 to 7:1 The ester eluent is separated by silica gel column chromatography to obtain a high-purity intermediate product. The product detection data is as follows: white solid, yield 86.0%

Reference： [1]Current Patent Assignee: LANZHOU UNIVERSITY - CN112358492, 2021, A Location in patent: Paragraph 0027-0030

76
[ 930-68-7 ]
[ 169590-42-5 ]
N-(3-oxocyclohexyl)-4-(3-(trifluoromethyl)-5-(4-(trifluoromethyl)phenyl)-1H-pyrazol-1-yl)benzenesulfonamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
61%	With 4-tolyl iodide; Selectfluor In acetonitrile at 20℃; for 16h;	General Procedure for hypervalent iodine-catalyzed conjugate addition reaction. General procedure: To an 8 mL vial equipped with a stir bar was added 4-iodotoluene (5 mg, 0.02 mmol), Selectfluor (14 mg, 0.04 mmol) and sulfonamide (0.2 mmol). Then solvent (MeCN, 0.4 mL) was added via a syringe, followed by enone (0.4 mmol). The reaction mixture was then stirred 16 h at room temperature. The reaction mixture was concentrated under reduced pressure to give the crude product, which was purified by column chromatography on silica gel to afford the pure product.

Reference： [1]Ariyarathna, Jeewani Poornima; Ziegelmeyer, Elizabeth Claire; Li, Wei [Arkivoc, 2021, vol. 2020, p. 67 - 78]

77
[ 169590-42-5 ]
[ 156899-14-8 ]
N-[1-(4-isobutylphenyl)ethyl]carbamoyl}-4-[5- (p-tolyl)-3-(trifluoromethyl)-1H-pyrazol-1-yl]benzenesulfonamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
39%	With triethylamine In N,N-dimethyl-formamide at 25℃; for 12h;	N-[1-(4-Isobutylphenyl)ethyl]carbamoyl}-4-[5-(p-tolyl)-3-(trifl uoromethyl)-1H-pyrazol-1-yl]benzenesulfonamide(4a). 1-Isobutyl-4-(1-isocyanatoethyl)-benzene (2), 0.1 g (0.52 mmol), and 0.2 mL of triethylaminewere added dropwise to 0.2 g (0.52 mmol) of4-[5-(4-methylphenyl)-3-(trifluoromethyl)pyrazol-1-yl]benzenesulfonamide (3a) in 5 mL of DMF. Thereaction mixture was allowed to stand at roomtemperature for 12 h and, after the addition of 5 mLof 1N HCl, it was stirred for 1 h. The white precipitatethat formed was fi ltered off, washed with water, andrecrystallized from ethanol. Yield 0.117 g (39%), mp65-67°C. 1H NMR spectrum (CDCl3),d, ppm: 0.84 d(6H,CH3CHCH3,J 6.6 Hz), 1.32 d (3H,CH3CHN,J6.7 Hz), 1.76-1.83 m (1H,CH3CHCH3),2.32 s (3H,CH3-Ph), 2.40 d (2H,CH2,J 7.2 Hz), 4.62-4.68 m (1H,CH3CHN),6.95 d (1H, NHCH, J 7.9 Hz), 7.05-7.13 m(4Harom),7.14-7.22 m(4Harom),7.20 s (1H, pyrazole),7.43 s (1H, NH-S), 7.53-7.59 m (4Harom).Found, %:C 61.65; H 5.35; N 9.55.C30H31F3N4O3S.Calculated,%: C 61.63; H 5.34; N 9.58. M 584.66.

Reference： [1]Burmistrov, V. V.; Butov, G. M.; D’yachenko, V. S.; Gladkikh, B. P. [Russian Journal of Organic Chemistry, 2021, vol. 57, # 5, p. 784 - 792][Zh. Org. Khim., 2021, vol. 57, # 5, p. 718 - 727]

78
[ 3303-84-2 ]
[ 169590-42-5 ]
C₂₅H₂₇F₃N₄O₅S [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
95%	With dmap; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; triethylamine In dichloromethane at 20℃;	1 Preparation of SZY1907-05: Add celecoxib (20.00g, 0.0525mol), DCM (400mL) to the three-necked flask, and then add Boc-β-alanine (0.0735mol), EDCI (0.121mol), triethylamine (0.158mol), DMAP (0.0164 mol); stirring at room temperature, TLC monitoring, until there is no raw material. Post-treatment: wash once with 3% dilute hydrochloric acid, wash once with saturated ammonium chloride, wash with saturated sodium chloride until neutral, The organic phase was dried with sodium sulfate and spin-dried to obtain a white solid; the white solid was dissolved in ethanol, and the same amount of water was added, and the temperature was heated and refluxed until it was completely dissolved. Slowly lower the temperature, precipitate the product, filter with suction, and dry to obtain SZY1907-05 with a yield of about 95% and a purity of greater than 98%. Status: White solid.

Reference： [1]Current Patent Assignee: SHANGHAI YINGNUO FUCHENG BIOTECHNOLOGY - CN113144212, 2021, A Location in patent: Paragraph 0033-0038

79
[ 124072-61-3 ]
[ 169590-42-5 ]
C₂₆H₂₉F₃N₄O₅S [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
1.3 g	With dmap; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; triethylamine In dichloromethane at 20℃;	1 Preparation of SZY1907-06: Add celecoxib (1.34g, 3.5mmol), DCM (26mL) to the three-necked flask, Add N-methyl-Boc-β-alanine (4.9 mmol), EDCI (8.05 mmol), triethylamine (10.5 mmol), DMAP (1 mmol) in sequence; stir at room temperature, monitored by TLC, until there is no raw material. Post-treatment: wash once with 3% dilute hydrochloric acid, wash once with saturated ammonium chloride, wash with saturated sodium chloride until neutral, dry the organic phase with sodium sulfate and spin dry to obtain a white solid; The white solid was stirred through the column, and the product was washed with dichloromethane/methanol to 30:1 (v/v), collected and spin-dried to obtain 1.3 g of white solid.

Reference： [1]Current Patent Assignee: SHANGHAI YINGNUO FUCHENG BIOTECHNOLOGY - CN113144212, 2021, A Location in patent: Paragraph 0065-0070

80
[ 104-54-1 ]
[ 169590-42-5 ]
C₂₆H₂₂F₃N₃O₂S [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
70%	With sodium hexaflorophosphate; magnesium triflate In tetrahydrofuran at 100℃; Schlenk technique;	3.1-3.2 (1) In a 10mL Schlenk tube, add 0.4 mmol cinnamyl alcohol, 0.8 mmol celecoxib, 0.04 mmol magnesium trifluoromethanesulfonate, 0.04 mmol of sodium hexafluorophosphate, add 4mL of tetrahydrofuran, stir and react in air at 100°C, the reaction equation is: (2) After TLC monitors that the reaction is complete, use a vacuum rotary evaporator to remove the solvent, and separate the product by thin-layer chromatography. The developing solvent is a petroleum ether/ethyl acetate system. The allylated product of Celecoxib is a pale yellow solid. 24, the yield was 70%.

Reference： [1]Current Patent Assignee: NANJING TECH UNIVERSITY - CN113277963, 2021, A Location in patent: Paragraph 0071-0076

81
[ 623-73-4 ]
[ 127-19-5 ]
[ 169590-42-5 ]
C₂₃H₂₂F₃N₃O₅S [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
47%	With iron(III) sulfate; potassium hydrogensulfate In cyclohexane at 90℃; for 24h;	23 Example 23 Add amide (0.5 mmol), sulfonamide (0.75 mmol), iron sulfate (20% mmol), potassium hydrogen sulfate (2.0 eq) to the test tube, then add cyclohexane (2 mL), and finally add ethyl diazoacetate EDA (3.0 mmol), the mixture was reacted at 90°C in an oil bath under an air atmosphere for 24 hours. After the reaction is completed, it is quenched with saturated sodium chloride solution, extracted with ethyl acetate, the organic phases are combined and dried over anhydrous magnesium sulfate, and the solvent is spin-dried under reduced pressure. The product can be obtained by column chromatography with a mixed solvent of ethyl acetate and petroleum ether with a yield of 47%. The main test data of the prepared product are as follows. Through analysis, it can be known that the actual synthesized product is consistent with the theoretical analysis.

Reference： [1]Current Patent Assignee: SOOCHOW UNIVERSITY (SUZHOU) - CN113527154, 2021, A Location in patent: Paragraph 0041-0042

82
[ 1119-51-3 ]
[ 169590-42-5 ]
N-(pent-4-en-1-yl)-4-(5-(p-tolyl)-3-(trifluoromethyl)-1H-pyrazol-1-yl)benzenesulfonamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
69%	With potassium carbonate In acetone at 60℃; for 12h; Inert atmosphere;
61%	With potassium carbonate; potassium iodide In acetone at 65℃; for 12h;	Compound 44a According to a literature procedure, an oven-dried 20-mL vial was charged with 5-bromopent-1-ene (0.67 g, 4.5 mmol), Celecoxib (1.0 g, 3.0 mmol), potassium carbonate (0.83 g, 6.0 mmol), potassium iodide (0.50 g, 0.3 mmol), 7.5 mL of dry acetone, and a magnetic stir bar. The reaction was heated at 65 °C for 12h and filtered. The product was purified by flash column chromatography (SiO2; 85:15 Hexanes:EA) to afford the corresponding compound 44a (818 mg, 61%) as a white solid.
	With potassium carbonate In acetonitrile for 7h; Reflux;

Reference： [1]Targos, Karina; Wang, Diana J.; Wickens, Zachary K. [Journal of the American Chemical Society, 2021, vol. 143, # 51, p. 21503 - 21510]
[2]Fan, Haoyu; Hartwig, John F.; Ma, Senjie; Roediger, Sven; Xi, Yumeng [Chem, 2022, vol. 8, # 2, p. 532 - 542]
[3]He, Xinxu; He, Yanyang; Qin, Xiaowen; Wu, Xiao-Feng; Yin, Zhiping [European Journal of Organic Chemistry, 2021, vol. 2021, # 42, p. 5831 - 5834]

83
[ 39267-79-3 ]
[ 169590-42-5 ]
N-(3-oxetanyl)-4-(5-(p-tolyl)-3-(trifluoromethyl)-1H-pyrazol-1-yl)benzenesulfonamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
87%	With 1,1,1,3,3,3-hexamethyl-2-(trimethylsilyl)-2-trisilanol; DBN; [Ir(3,5-difluoro-2-[5-(trifluoromethyl)-2-pyridinyl]phenyl)₂(4,4'-bis(trifluoromethyl)bipyridine)]PF₆; water; bis(2,2,6,6-tetramethyl-3,5-heptadionato) copper(II); lithium tert-butoxide In acetonitrile at 20℃; for 4h; Sealed tube; Irradiation; regioselective reaction;	General procedure B: General procedure: To an oven-dried 40 mL vial equipped with a Teflon stir bar was added Nnucleophile(0.25 mmol, 1.0 equiv.), Ir[dF(CF3)ppy]2[4,4¢-d(CF3)bpy]PF6 ([Ir-1], 2.0 μmol, 0.008 equiv.),MeCN (2.5 mL, 0.1 M) and 1,5-diazabicyclo[4.3.0]non-5-ene (DBN, 0.25 mmol, 1.0 equiv.) The resultinghomogeneous solution was stirred for 5 minutes, after which LiOt-Bu (0.75 mmol, 3.0 equiv.) and water(2.5 mmol, 10 equiv.) were added to the vial. This suspension was then sonicated under air for 1 minuteuntil the mixture became homogeneous. Cu(TMHD)2 (0.05-0.15 mmol, 0.2-0.6 equiv.) was then added tothe vial, and the solution was stirred for 1-2 minutes under air to ensure complete ligation of thenucleophile to the copper precatalyst. Following this complexation period, alkyl halide (0.625 mmol, 2.5equiv.) and silyl radical precursor (0.625 mmol, 2.5 equiv.) were added to the mixture, after which the vialwas capped and an 18G vent needle was inserted through the Teflon-lined septum. The reaction mixturewas subsequently stirred under air within the Integrated Photoreactor (450 nm irradiation) for 4 hours(settings for light intensity, fan speed and stir rate are indicated for each substrate). After 4 hours, thereaction mixture was diluted with EtOAc (5 mL), followed by the addition of KF on alumina (40 wt. %, 1.0g) and tetrabutylammonium bromide (500 mg) to the vial. This suspension was stirred under air for 2-24hours, then filtered into a separatory funnel, using an additional 25 mL EtOAc wash to ensure completetransfer from the vial. The organic layer was subsequently washed with saturated Na2CO3 (10 mL), water(10 mL) and brine (10 mL), and the collected aqueous layer was extracted with EtOAc (10 mL). Thecombined organics were dried over MgSO4 and concentrated in vacuo to obtain the crude product. Thisresidue was purified by flash chromatography and/or preparative thin-layer chromatography on silica gelto afford the desired N-alkylated product.

Reference： [1]Cabré, Albert; Dow, Nathan W.; MacMillan, David W. C. [Chem, 2021, vol. 7, # 7, p. 1827 - 1842]

84
[ 4333-56-6 ]
[ 169590-42-5 ]
N-cycloproyl-4-(5-(p-tolyl)-3-(trifluoromethyl)-1H-pyrazol-1-yl)benzenesulfonamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
51%	With 1,1,1,3,3,3-hexamethyl-2-(trimethylsilyl)-2-trisilanol; DBN; [Ir(3,5-difluoro-2-[5-(trifluoromethyl)-2-pyridinyl]phenyl)₂(4,4'-bis(trifluoromethyl)bipyridine)]PF₆; water; bis(2,2,6,6-tetramethyl-3,5-heptadionato) copper(II); lithium tert-butoxide In acetonitrile at 20℃; for 4h; Sealed tube; Irradiation; regioselective reaction;	General procedure B: General procedure: To an oven-dried 40 mL vial equipped with a Teflon stir bar was added Nnucleophile(0.25 mmol, 1.0 equiv.), Ir[dF(CF3)ppy]2[4,4¢-d(CF3)bpy]PF6 ([Ir-1], 2.0 μmol, 0.008 equiv.),MeCN (2.5 mL, 0.1 M) and 1,5-diazabicyclo[4.3.0]non-5-ene (DBN, 0.25 mmol, 1.0 equiv.) The resultinghomogeneous solution was stirred for 5 minutes, after which LiOt-Bu (0.75 mmol, 3.0 equiv.) and water(2.5 mmol, 10 equiv.) were added to the vial. This suspension was then sonicated under air for 1 minuteuntil the mixture became homogeneous. Cu(TMHD)2 (0.05-0.15 mmol, 0.2-0.6 equiv.) was then added tothe vial, and the solution was stirred for 1-2 minutes under air to ensure complete ligation of thenucleophile to the copper precatalyst. Following this complexation period, alkyl halide (0.625 mmol, 2.5equiv.) and silyl radical precursor (0.625 mmol, 2.5 equiv.) were added to the mixture, after which the vialwas capped and an 18G vent needle was inserted through the Teflon-lined septum. The reaction mixturewas subsequently stirred under air within the Integrated Photoreactor (450 nm irradiation) for 4 hours(settings for light intensity, fan speed and stir rate are indicated for each substrate). After 4 hours, thereaction mixture was diluted with EtOAc (5 mL), followed by the addition of KF on alumina (40 wt. %, 1.0g) and tetrabutylammonium bromide (500 mg) to the vial. This suspension was stirred under air for 2-24hours, then filtered into a separatory funnel, using an additional 25 mL EtOAc wash to ensure completetransfer from the vial. The organic layer was subsequently washed with saturated Na2CO3 (10 mL), water(10 mL) and brine (10 mL), and the collected aqueous layer was extracted with EtOAc (10 mL). Thecombined organics were dried over MgSO4 and concentrated in vacuo to obtain the crude product. Thisresidue was purified by flash chromatography and/or preparative thin-layer chromatography on silica gelto afford the desired N-alkylated product.

Reference： [1]Cabré, Albert; Dow, Nathan W.; MacMillan, David W. C. [Chem, 2021, vol. 7, # 7, p. 1827 - 1842]

85
[ 109-65-9 ]
[ 169590-42-5 ]
N-butyl-celecoxib [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
90%	With potassium carbonate; potassium iodide In acetone at 80℃; for 30h;

Reference： [1]Cao, Tongxiang; Chen, Kai; Lu, Jiajun; Ma, Jun; Wu, Rui; Zhu, Shifa [Journal of the American Chemical Society, 2021, vol. 143, # 36, p. 14916 - 14925]

86
[ 942-54-1 ]
[ 169590-42-5 ]
C₂₅H₂₂F₃N₃O₃S [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
96%	With Isobutyronitrile; copper(II) bis(trifluoromethanesulfonate); sodium phosphate In dichloromethane at 20℃; for 24h; Irradiation; Inert atmosphere; Sealed tube;	General procedure for sulfonamidation General procedure: An oven-dried 6-ml vial equipped witha stir bar was placed in a nitrogen-filled glovebox and charged with Cu(OTf)2 (180.8 mg, 2.5 equiv., 0.50 mmol), Na3PO4 (98.2 mg, 3.0 equiv., 0.60 mmol), the sulfonamide nucleophile (1.5-3.0 equiv.), carboxylic acid (1.0 equiv., 0.20 mmol), methylene chloride (2.0 ml, 0.10 M) and isobutyronitrile (100 μl, 5.5 equiv.,1.1 mmol). The vial was sealed with a screwcap bearing a Teflon septum, removed from the glovebox and placed on a stir plate. The vial was irradiated at 427 nm with two 40-W Kessil PR160 lamps at a distance of 10 cm with stirring at 800 r.p.m. A fan was used to maintain the vial at room temperature. After 24 h, the crude reaction mixture was diluted with 1.5 ml of EtOAc and adsorbed directly on diatomaceous earth (Celite). The product was purified by flash chromatography on silica gel, eluting with mixtures of ethyl acetate and hexanes.

Reference： [1]Li, Qi Yukki; Gockel, Samuel N.; Lutovsky, Grace A.; DeGlopper, Kimberly S.; Baldwin, Neil J.; Bundesmann, Mark W.; Tucker, Joseph W.; Bagley, Scott W.; Yoon, Tehshik P. [Nature Chemistry, 2022, vol. 14, # 1, p. 94 - 99]

87
[ 110-52-1 ]
[ 169590-42-5 ]
C₂₁H₂₀F₃N₃O₂S [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
99%	With potassium carbonate In acetonitrile Reflux;

Reference： [1]Ho, Justin S. K.; Lin, Song; Liu, Kaida; Mao, Kaining; Neurock, Matthew; Novaes, Luiz F. T.; Tanwar, Mayank; Terrett, Jack A.; Villemure, Elisia [Journal of the American Chemical Society, 2022, vol. 144, # 3, p. 1187 - 1197]

88
[ 720-94-5 ]
[ 701-34-8 ]
[ 169590-42-5 ]

Yield	Reaction Conditions	Operation in experiment
87.7%	With hydrazine hydrate monohydrate; triethylamine In methanol; water monomer at 20℃; for 12h; Reflux;	1.b-1.c; 2.b-2.c; 3.b-3.c b) In a 5000ml reaction flask, add the evaporated-to-dry product of step a), 2300g of 70% methanol water, 90g of hydrazine hydrate (80%), 260g of p-bromobenzenesulfonamide, 120g of triethylamine, heated to reflux temperature, and reacted for 12 hours, cooled to room temperature, a large amount of white solids were precipitated, and 400 g of wet product was obtained by suction filtration; c) 400g of the obtained product wet product and 3000g of 70% methanol water were added to the reaction flask, the temperature was raised and refluxed until all dissolved, mechanical impurities were removed by suction filtration while hot, slowly cooled for crystallization, suction filtration, washed with water, and dried to obtain 335g of product , the obtained product has a single impurity ≤ 0.1%, a purity of 99.7%, and the total yield of the three-step process is 87.7% calculated as ethyl trifluoroacetoacetate.

Reference： [1]Current Patent Assignee: SHANDONG PLATINUM SOURCE PHARMACEUTICAL - CN114195714, 2022, A Location in patent: Paragraph 0021; 0036; 0038; 0040; 0042-0044; 0046-0047

Type	HazMat fee for 500 gram (Estimated)
Excepted Quantity	USD 0.00
Limited Quantity	USD 15-60
Inaccessible (Haz class 6.1), Domestic	USD 80+
Inaccessible (Haz class 6.1), International	USD 150+
Accessible (Haz class 3, 4, 5 or 8), Domestic	USD 100+
Accessible (Haz class 3, 4, 5 or 8), International	USD 200+

Purity	Size	Price	VIP Price	USA Stock *0-1 Day	Global Stock *5-7 Days	Quantity
{[ item.p_purity ]}	{[ item.pr_size ]}	{[ getRatePrice(item.pr_usd, 1,1) ]} {[ getRatePrice(item.pr_usd,item.pr_rate,item.mem_rate) ]}	{[ getRatePrice(item.pr_usd, 1,1) ]}	Inquiry {[ getRatePrice(item.pr_usd,item.pr_rate,item.mem_rate) ]} {[ getRatePrice(item.pr_usd,1,item.mem_rate) ]}	{[ item.pr_usastock ]}	Inquiry -	{[ item.pr_chinastock ]}	Inquiry -

CAS No. :	169590-42-5	MDL No. :	MFCD00941298
Formula :	C₁₇H₁₄F₃N₃O₂S	Boiling Point :	-
Linear Structure Formula :	-	InChI Key :	RZEKVGVHFLEQIL-UHFFFAOYSA-N
M.W :	381.37	Pubchem ID :	2662
Synonyms :	SC 58635;YM-177;Xilebao.;brand name Celebrex;YM177. Celecoxib

Num. heavy atoms :	26
Num. arom. heavy atoms :	17
Fraction Csp3 :	0.12
Num. rotatable bonds :	4
Num. H-bond acceptors :	7.0
Num. H-bond donors :	1.0
Molar Refractivity :	89.96
TPSA :	86.36 Å²

GI absorption :	High
BBB permeant :	No
P-gp substrate :	No
CYP1A2 inhibitor :	Yes
CYP2C19 inhibitor :	No
CYP2C9 inhibitor :	Yes
CYP2D6 inhibitor :	No
CYP3A4 inhibitor :	No
Log Kp (skin permeation) :	-6.21 cm/s

[ CAS No. 169590-42-5 ] {[proInfo.proName]}

Quality Control of [ 169590-42-5 ]

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Product Details of [ 169590-42-5 ]

Calculated chemistry of [ 169590-42-5 ]

Physicochemical Properties

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Lipophilicity

Druglikeness

Water Solubility

Medicinal Chemistry

Safety of [ 169590-42-5 ]

Application In Synthesis of [ 169590-42-5 ]

[ 169590-42-5 ] Synthesis Path-Downstream 1~88

Precautionary Statements-General

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Log Po/w (iLOGP) :	2.56
Log Po/w (XLOGP3) :	3.4
Log Po/w (WLOGP) :	5.75
Log Po/w (MLOGP) :	2.65
Log Po/w (SILICOS-IT) :	2.63
Consensus Log Po/w :	3.4

Lipinski :	0.0
Ghose :	None
Veber :	0.0
Egan :	0.0
Muegge :	0.0
Bioavailability Score :	0.55

Log S (ESOL) :	-4.57
Solubility :	0.0104 mg/ml ; 0.0000271 mol/l
Class :	Moderately soluble
Log S (Ali) :	-4.89
Solubility :	0.00488 mg/ml ; 0.0000128 mol/l
Class :	Moderately soluble
Log S (SILICOS-IT) :	-6.22
Solubility :	0.000229 mg/ml ; 0.000000601 mol/l
Class :	Poorly soluble

PAINS :	0.0 alert
Brenk :	0.0 alert
Leadlikeness :	1.0
Synthetic accessibility :	2.74

Signal Word:	Danger	Class:	9
Precautionary Statements:	P201-P202-P260-P273-P280-P308+P313-P391-P405-P501	UN#:	3077
Hazard Statements:	H360-H373-H401-H410	Packing Group:	Ⅲ
GHS Pictogram:

Precautionary Statements-General
Code	Phrase
P101	If medical advice is needed,have product container or label at hand.
P102	Keep out of reach of children.
P103	Read label before use
Prevention
Code	Phrase
P201	Obtain special instructions before use.
P202	Do not handle until all safety precautions have been read and understood.
P210	Keep away from heat/sparks/open flames/hot surfaces. - No smoking.
P211	Do not spray on an open flame or other ignition source.
P220	Keep/Store away from clothing/combustible materials.
P221	Take any precaution to avoid mixing with combustibles
P222	Do not allow contact with air.
P223	Keep away from any possible contact with water, because of violent reaction and possible flash fire.
P230	Keep wetted
P231	Handle under inert gas.
P232	Protect from moisture.
P233	Keep container tightly closed.
P234	Keep only in original container.
P235	Keep cool
P240	Ground/bond container and receiving equipment.
P241	Use explosion-proof electrical/ventilating/lighting/equipment.
P242	Use only non-sparking tools.
P243	Take precautionary measures against static discharge.
P244	Keep reduction valves free from grease and oil.
P250	Do not subject to grinding/shock/friction.
P251	Pressurized container: Do not pierce or burn, even after use.
P260	Do not breathe dust/fume/gas/mist/vapours/spray.
P261	Avoid breathing dust/fume/gas/mist/vapours/spray.
P262	Do not get in eyes, on skin, or on clothing.
P263	Avoid contact during pregnancy/while nursing.
P264	Wash hands thoroughly after handling.
P265	Wash skin thouroughly after handling.
P270	Do not eat, drink or smoke when using this product.
P271	Use only outdoors or in a well-ventilated area.
P272	Contaminated work clothing should not be allowed out of the workplace.
P273	Avoid release to the environment.
P280	Wear protective gloves/protective clothing/eye protection/face protection.
P281	Use personal protective equipment as required.
P282	Wear cold insulating gloves/face shield/eye protection.
P283	Wear fire/flame resistant/retardant clothing.
P284	Wear respiratory protection.
P285	In case of inadequate ventilation wear respiratory protection.
P231 + P232	Handle under inert gas. Protect from moisture.
P235 + P410	Keep cool. Protect from sunlight.
Response
Code	Phrase
P301	IF SWALLOWED:
P304	IF INHALED:
P305	IF IN EYES:
P306	IF ON CLOTHING:
P307	IF exposed:
P308	IF exposed or concerned:
P309	IF exposed or if you feel unwell:
P310	Immediately call a POISON CENTER or doctor/physician.
P311	Call a POISON CENTER or doctor/physician.
P312	Call a POISON CENTER or doctor/physician if you feel unwell.
P313	Get medical advice/attention.
P314	Get medical advice/attention if you feel unwell.
P315	Get immediate medical advice/attention.
P320
P302 + P352	IF ON SKIN: wash with plenty of soap and water.
P321
P322
P330	Rinse mouth.
P331	Do NOT induce vomiting.
P332	IF SKIN irritation occurs:
P333	If skin irritation or rash occurs:
P334	Immerse in cool water/wrap n wet bandages.
P335	Brush off loose particles from skin.
P336	Thaw frosted parts with lukewarm water. Do not rub affected area.
P337	If eye irritation persists:
P338	Remove contact lenses, if present and easy to do. Continue rinsing.
P340	Remove victim to fresh air and keep at rest in a position comfortable for breathing.
P341	If breathing is difficult, remove victim to fresh air and keep at rest in a position comfortable for breathing.
P342	If experiencing respiratory symptoms:
P350	Gently wash with plenty of soap and water.
P351	Rinse cautiously with water for several minutes.
P352	Wash with plenty of soap and water.
P353	Rinse skin with water/shower.
P360	Rinse immediately contaminated clothing and skin with plenty of water before removing clothes.
P361	Remove/Take off immediately all contaminated clothing.
P362	Take off contaminated clothing and wash before reuse.
P363	Wash contaminated clothing before reuse.
P370	In case of fire:
P371	In case of major fire and large quantities:
P372	Explosion risk in case of fire.
P373	DO NOT fight fire when fire reaches explosives.
P374	Fight fire with normal precautions from a reasonable distance.
P376	Stop leak if safe to do so. Oxidising gases (section 2.4) 1
P377	Leaking gas fire: Do not extinguish, unless leak can be stopped safely.
P378
P380	Evacuate area.
P381	Eliminate all ignition sources if safe to do so.
P390	Absorb spillage to prevent material damage.
P391	Collect spillage. Hazardous to the aquatic environment
P301 + P310	IF SWALLOWED: Immediately call a POISON CENTER or doctor/physician.
P301 + P312	IF SWALLOWED: call a POISON CENTER or doctor/physician IF you feel unwell.
P301 + P330 + P331	IF SWALLOWED: Rinse mouth. Do NOT induce vomiting.
P302 + P334	IF ON SKIN: Immerse in cool water/wrap in wet bandages.
P302 + P350	IF ON SKIN: Gently wash with plenty of soap and water.
P303 + P361 + P353	IF ON SKIN (or hair): Remove/Take off Immediately all contaminated clothing. Rinse SKIN with water/shower.
P304 + P312	IF INHALED: Call a POISON CENTER or doctor/physician if you feel unwell.
P304 + P340	IF INHALED: Remove victim to fresh air and Keep at rest in a position comfortable for breathing.
P304 + P341	IF INHALED: If breathing is difficult, remove victim to fresh air and keep at rest in a position comfortable for breathing.
P305 + P351 + P338	IF IN EYES: Rinse cautiously with water for several minutes. Remove contact lenses, if present and easy to do. Continue rinsing.
P306 + P360	IF ON CLOTHING: Rinse Immediately contaminated CLOTHING and SKIN with plenty of water before removing clothes.
P307 + P311	IF exposed: call a POISON CENTER or doctor/physician.
P308 + P313	IF exposed or concerned: Get medical advice/attention.
P309 + P311	IF exposed or if you feel unwell: call a POISON CENTER or doctor/physician.
P332 + P313	IF SKIN irritation occurs: Get medical advice/attention.
P333 + P313	IF SKIN irritation or rash occurs: Get medical advice/attention.
P335 + P334	Brush off loose particles from skin. Immerse in cool water/wrap in wet bandages.
P337 + P313	IF eye irritation persists: Get medical advice/attention.
P342 + P311	IF experiencing respiratory symptoms: call a POISON CENTER or doctor/physician.
P370 + P376	In case of fire: Stop leak if safe to Do so.
P370 + P378	In case of fire:
P370 + P380	In case of fire: Evacuate area.
P370 + P380 + P375	In case of fire: Evacuate area. Fight fire remotely due to the risk of explosion.
P371 + P380 + P375	In case of major fire and large quantities: Evacuate area. Fight fire remotely due to the risk of explosion.
Storage
Code	Phrase
P401
P402	Store in a dry place.
P403	Store in a well-ventilated place.
P404	Store in a closed container.
P405	Store locked up.
P406	Store in corrosive resistant/ container with a resistant inner liner.
P407	Maintain air gap between stacks/pallets.
P410	Protect from sunlight.
P411
P412	Do not expose to temperatures exceeding 50 oC/ 122 oF.
P413
P420	Store away from other materials.
P422
P402 + P404	Store in a dry place. Store in a closed container.
P403 + P233	Store in a well-ventilated place. Keep container tightly closed.
P403 + P235	Store in a well-ventilated place. Keep cool.
P410 + P403	Protect from sunlight. Store in a well-ventilated place.
P410 + P412	Protect from sunlight. Do not expose to temperatures exceeding 50 oC/122oF.
P411 + P235	Keep cool.
Disposal
Code	Phrase
P501	Dispose of contents/container to ...
P502	Refer to manufacturer/supplier for information on recovery/recycling