Name: 328-42-7|Oxalacetic Acid|97%
Brand: Ambeed
SKU: A333802
Price: 5.0 USD
Availability: InStock
Rating: 92 (28 reviews)

1
[ 51304-64-4 ]
[ 328-42-7 ]
[ 100133-65-1 ]

Reference： [1]Helvetica Chimica Acta,1959,vol. 42,p. 1201,1203

2
[ 67-56-1 ]
[ 328-42-7 ]
[ 25007-54-9 ]

Reference： [1]Journal of the Chemical Society,1900,vol. 77,p. 81
Journal of the Chemical Society,1901,vol. 79,p. 91
[2]Tetrahedron Asymmetry,1999,vol. 10,p. 2713 - 2728
[3]International Journal of Chemical Kinetics,2001,vol. 33,p. 431 - 439

3
[ 328-42-7 ]
[ 7512-17-6 ]
[ 131-48-6 ]

Reference： [1]Biochemical Journal,1958,vol. 68,p. 57,59

4
[ 328-42-7 ]
[ 37832-55-6 ]

Reference： [1]Journal of the Chemical Society,1901,vol. 79,p. 94

5
[ 328-42-7 ]
[ 617-45-8 ]

Reference： [1]Hoppe-Seyler's Zeitschrift fur Physiologische Chemie,1925,vol. 148,p. 311
Hoppe-Seyler's Zeitschrift fuer Physiologische Chemie,1927,vol. 170,p. 187,195
[2]Analytical Chemistry,2010,vol. 82,p. 2082 - 2086
[3]Chemical Communications,2019,vol. 55,p. 14721 - 14724

6
[ 328-42-7 ]
[ 300-85-6 ]
[ 77-92-9 ]

Reference： [1]Journal of Biological Chemistry,1948,vol. 176,p. 101

7
[ 328-42-7 ]
[ 453-17-8 ]
[ 56742-44-0 ]
[ 17510-99-5 ]

Reference： [1]Carbohydrate Research,1968,vol. 8,p. 193 - 204

8
[ 328-42-7 ]
[ 453-17-8 ]
[ 17510-99-5 ]

Reference： [1]Carbohydrate Research,1968,vol. 8,p. 193 - 204

9
[ 67-56-1 ]
[ 328-42-7 ]
[ 18830-44-9 ]
[ 102526-15-8 ]
[ 102526-14-7 ]

Reference： [1]Journal of Organic Chemistry USSR (English Translation),1985,vol. 21,p. 1286 - 1291
Zhurnal Organicheskoi Khimii,1985,vol. 21,p. 1414 - 1420
[2]Journal of Organic Chemistry USSR (English Translation),1985,vol. 21,p. 1286 - 1291
Zhurnal Organicheskoi Khimii,1985,vol. 21,p. 1414 - 1420

10
[ 328-42-7 ]
[ 453-17-8 ]
[ 138320-51-1 ]
[ 138320-51-1 ]

Reference： [1]Carbohydrate Research,1989,vol. 188,p. 97 - 104

11
[ 328-42-7 ]
[ 609-06-3 ]
[ 123672-56-0 ]

Reference： [1]Carbohydrate Research,1993,vol. 238,p. 93 - 107

12
[ 328-42-7 ]
[ 1866-15-5 ]
[ 77-92-9 ]

Reference： [1]Journal of Organic Chemistry,1991,vol. 56,p. 3752 - 3755

13
[ 328-42-7 ]
[ 74-88-4 ]
[ 3952-66-7 ]

Reference： [1]Journal of Organic Chemistry,1981,vol. 46,p. 4980 - 4987

14
[ 328-42-7 ]
[ 72915-12-9 ]
[ 25561-30-2 ]
[ 354-38-1 ]
[ 55982-15-5 ]
C₁₇H₂₂F₅NO₅Si₂ [ No CAS ]

Reference： [1]Environmental Science and Technology,1998,vol. 32,p. 2357 - 2370

15
[ 6066-82-6 ]
[ 328-42-7 ]
[ 675594-69-1 ]

Yield	Reaction Conditions	Operation in experiment
	With N-(3-dimethylaminopropyl)-N-ethylcarbodiimide In DMF (N,N-dimethyl-formamide) at 20℃; for 24h;	5-1 Example 5-1; To a 5 wt% DMF solution of oxalacetic acid, 2.2 equivalents of N-hydroxysuccinimide and 2.1 equivalents of EDC were added at room temperature. The resulting mixture was stirred for 24 hours. Subsequently, only the DMF, i.e., the organic solvent in the reaction solution, was removed by reduced-pressure distillation. The residue was purified with an acetone/n-hexane developing solvent by chromatography over a silica gel column to obtain a derivative having two carboxyl groups of oxalacetic acid modified with N-hydroxysuccinimide.

Reference： [1]Current Patent Assignee: NATIONAL INSTITUTE FOR MATERIALS SCIENCE; ENEOS HOLDINGS INC - EP1548004, 2005, A1 Location in patent: Page/Page column 7

16
[ 67-56-1 ]
[ 328-42-7 ]
C₆H₈O₅ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
93%	With thionyl chloride at 0℃; for 2h; Heating / reflux;	135.A Step A. Commercially available 2-oxo-succinic acid (15 g) was dissolved inMeOH (150 mL) and cooled to 0 °C. Thionylchloride (14 mL) was carefully added and the mixture was heated to reflux for 2 h and concentrated. The residue was dried to give the title compound as a solid (16.9 g, 93%). [MH]+ = 161.

Reference： [1]Current Patent Assignee: AMGEN INC - WO2008/63671, 2008, A2 Location in patent: Page/Page column 185

17
[ 142-45-0 ]
[ 328-42-7 ]

Yield	Reaction Conditions	Operation in experiment
78%	With water at 80℃; for 12h;	7 [Example 7]; 0.1 mmol of water-soluble acetylene carboxylic acids whose R1 is COOH and R2 is H in Fig. 1 (a) was mixed with 2 mL of aqueous solution containing 3.1 mg (2.5 µmol) of di[triaqua {2,6-di(phenylthiomethyl)pyridine} ruthenium (III)] 3-sulphate, and the mixture was reacted at the pH 2.0 at 80°C under argon atmosphere for 12 hours. The resulting mixture was condensed to give a product. The product was analyzed by 1H NMR.
70%	With water at 80℃; for 12h;	5 [Example 5]; 0.1 mmol of water-soluble acetylene carboxylic acids whose R1 is COOH and R2 is H in Fig. 1(a) was mixed with 2 mL of aqueous solution containing 5.0 µmol of ruthenium trichloride, and the mixture was reacted at the pH 2.0 at 80°C under argon atmosphere for 12 hours. The resulting mixture was condensed to give a product. The product was analyzed by 1H NMR.
57%	With water at 80℃; for 12h;	8 [Example 8]; 0.1 mmol of water-soluble acetylene carboxylic acids whose R1 is COOH and R2 is H in Fig. 1(a) was mixed with 2 mL of aqueous solution containing 3.1 mg (2.5 µmol) of di[triaqua {2,6-di(phenylthiomethyl)pyridine} rhodium (III)] 3-sulphate, and the mixture was reacted at the pH 2.0 at 80°C under argon atmosphere for 12 hours. The resulting mixture was condensed to give a product. The product was analyzed by 1H NMR.

40%	With water at 80℃; for 12h;	6 [Example 6]; 0.1 mmol of water-soluble acetylene carboxylic acids whose R1 is COOH and R2 is H in Fig. 1(a) was mixed with 2 mL of aqueous solution containing 5.0 µmol of rhodium trichloride, and the mixture was reacted at the pH 2.0 at 80°C under argon atmosphere for 12 hours. The resulting mixture was condensed to give a product. The product was analyzed by 1H NMR.
25%	With water at 80℃; for 12h;	2 [Comparative Example 2]; The same operation as in Examples 5 to 8 except that HgSO4 was used as a catalyst.

Reference： [1]Current Patent Assignee: JAPAN SCIENCE AND TECHNOLOGY AGENCY - EP1932824, 2008, A1 Location in patent: Page/Page column 17; 19
[2]Current Patent Assignee: JAPAN SCIENCE AND TECHNOLOGY AGENCY - EP1932824, 2008, A1 Location in patent: Page/Page column 17; 19
[3]Current Patent Assignee: JAPAN SCIENCE AND TECHNOLOGY AGENCY - EP1932824, 2008, A1 Location in patent: Page/Page column 17; 19
[4]Current Patent Assignee: JAPAN SCIENCE AND TECHNOLOGY AGENCY - EP1932824, 2008, A1 Location in patent: Page/Page column 17; 19
[5]Current Patent Assignee: JAPAN SCIENCE AND TECHNOLOGY AGENCY - EP1932824, 2008, A1 Location in patent: Page/Page column 17; 19

18
[ 14371-10-9 ]
[ 328-42-7 ]
[ 1034123-72-2 ]

Yield	Reaction Conditions	Operation in experiment
35%	Stage #1: (E)-3-phenylpropenal With macrophomate synthase from Macrophoma commelinae; magnesium chloride In acetonitrile at 20℃; for 0.166667h; aq. phosphate buffer; Enzymatic reaction; Stage #2: Oxalacetic acid In acetonitrile for 7h; aq. phosphate buffer; Enzymatic reaction;

Reference： [1]Serafimov, Joerg M.; Gillingham, Dennis; Kuster, Simon; Hilvert, Donald [Journal of the American Chemical Society, 2008, vol. 130, # 25, p. 7798 - 7799]

19
[ 97-96-1 ]
[ 328-42-7 ]
[ 1034123-77-7 ]

Yield	Reaction Conditions	Operation in experiment
45%	Stage #1: 2-Ethylbutyraldehyde With macrophomate synthase from Macrophoma commelinae; magnesium chloride In acetonitrile at 20℃; for 0.166667h; aq. phosphate buffer; Enzymatic reaction; Stage #2: Oxalacetic acid In acetonitrile for 7h; aq. phosphate buffer; Enzymatic reaction;

Reference： [1]Serafimov, Joerg M.; Gillingham, Dennis; Kuster, Simon; Hilvert, Donald [Journal of the American Chemical Society, 2008, vol. 130, # 25, p. 7798 - 7799]

20
[ 328-42-7 ]
[ 78669-40-6 ]
[ 1034123-75-5 ]

Yield	Reaction Conditions	Operation in experiment
48%	Stage #1: (6E)-6,8-nonadienal With macrophomate synthase from Macrophoma commelinae; magnesium chloride In acetonitrile at 20℃; for 0.166667h; aq. phosphate buffer; Enzymatic reaction; Stage #2: Oxalacetic acid In acetonitrile for 7h; aq. phosphate buffer; Enzymatic reaction;

Reference： [1]Serafimov, Joerg M.; Gillingham, Dennis; Kuster, Simon; Hilvert, Donald [Journal of the American Chemical Society, 2008, vol. 130, # 25, p. 7798 - 7799]

21
[ 328-42-7 ]
[ 2687-43-6 ]
N-benzyloxy-α-iminosuccinic acid [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
63%	With sodium acetate In methanol; water at 20℃; for 18h;	N-Benzyloxy-α-iminosuccinic acid (4e) Sodium acetate (807 mg, 9.8 mmol) was added to a solution of oxaloacetic acid (650 mg, 4.9 mmol) and o-benzylhydroxylamine hydrochloride (2.0 eq) in 20 mL of H2O/MeOH (1:1). The mixture was vigorously stirred at room temperature for 18 hrs. Methanol was evaporated and aqueos layer was extracted with ethyl acetate. 10 mL saturated solution of NaHCO3 was added to organic layer and the two layers were separated. The aqueous layer was acidified with 10% HCl at 0°C and extracted with ethyl acetate. The combined organic layers were dried over MgSO4 and concentrated to give a pale yellow solid (730 mg, 63%). 1H NMR (500 M Hz, CD3OD) δ 7.38-7.23 (m, 5H), 5.27 (s, 2H), 3.59 (s, 2H); 13C NMR (125 M Hz, CD3OD) δ 171.8, 165.6, 147.4, 137.9, 129.5, 129.5, 129.4, 78.8, 31.8.

Reference： [1]Tibrewal, Nidhi; Elliott, Gregory I. [Bioorganic and Medicinal Chemistry Letters, 2011, vol. 21, # 1, p. 517 - 519]

22
[ 98-01-1 ]
[ 328-42-7 ]
[ 17356-08-0 ]
[ 1268854-61-0 ]

Yield	Reaction Conditions	Operation in experiment
93%	With trifluoroacetic acid In tetrahydrofuran at 95℃; for 0.25h; Microwave irradiation; Sealed tube;	4.2. General procedure for the synthesis of 6a-6l General procedure: To a mixture of oxalacetic acid (2.6 mmol), aldehyde (2.0 mmol), and urea/thiourea (2.6 mmol) in THF (3 mL) was added TFA (0.10 mL). The mixture was heated at 95 °C for 15 min using microwave irradiation in a sealed tube. Thereafter, the mixture was cooled and the solvent was removed under reduced pressure. The residue obtained was washed with Et2O and dried under vacuum to afford the final product.

Reference： [1]Location in patent: experimental part Fang, Zhanxiong; Lam, Yulin [Tetrahedron, 2011, vol. 67, # 6, p. 1294 - 1297]

23
[ 98-01-1 ]
[ 328-42-7 ]
[ 57-13-6 ]
[ 1268854-65-4 ]

Yield	Reaction Conditions	Operation in experiment
83%	With trifluoroacetic acid In tetrahydrofuran at 95℃; for 0.25h; Microwave irradiation; Sealed tube;	4.2. General procedure for the synthesis of 6a-6l General procedure: To a mixture of oxalacetic acid (2.6 mmol), aldehyde (2.0 mmol), and urea/thiourea (2.6 mmol) in THF (3 mL) was added TFA (0.10 mL). The mixture was heated at 95 °C for 15 min using microwave irradiation in a sealed tube. Thereafter, the mixture was cooled and the solvent was removed under reduced pressure. The residue obtained was washed with Et2O and dried under vacuum to afford the final product.

Reference： [1]Location in patent: experimental part Fang, Zhanxiong; Lam, Yulin [Tetrahedron, 2011, vol. 67, # 6, p. 1294 - 1297]

24
[ 98-03-3 ]
[ 328-42-7 ]
[ 17356-08-0 ]
[ 1268854-62-1 ]

Yield	Reaction Conditions	Operation in experiment
76%	With trifluoroacetic acid In tetrahydrofuran at 95℃; for 0.25h; Microwave irradiation; Sealed tube;	4.2. General procedure for the synthesis of 6a-6l General procedure: To a mixture of oxalacetic acid (2.6 mmol), aldehyde (2.0 mmol), and urea/thiourea (2.6 mmol) in THF (3 mL) was added TFA (0.10 mL). The mixture was heated at 95 °C for 15 min using microwave irradiation in a sealed tube. Thereafter, the mixture was cooled and the solvent was removed under reduced pressure. The residue obtained was washed with Et2O and dried under vacuum to afford the final product.

Reference： [1]Location in patent: experimental part Fang, Zhanxiong; Lam, Yulin [Tetrahedron, 2011, vol. 67, # 6, p. 1294 - 1297]

25
[ 109-57-9 ]
[ 328-42-7 ]
[ 587-04-2 ]
[ 1268854-69-8 ]

Yield	Reaction Conditions	Operation in experiment
75%	With trifluoroacetic acid In tetrahydrofuran at 95℃; for 0.25h; Microwave irradiation; Sealed tube; chemoselective reaction;	4.3. General procedure for the synthesis of 6m-6w General procedure: To a mixture of oxalacetic acid (2.6 mmol), aldehyde (2.0 mmol) and N-substituted urea/thiourea (2.6 mmol) in THF (3 mL) was added TFA (0.10 mL). The mixture was heated at 95 °C for 15 min using microwave irradiation in a sealed tube. Thereafter, the mixture was cooled and the solvent was removed under reduced pressure. 0.5 M NaOH (20 mL) was then added to the residue and the resulting solution was extracted with EtOAc (3×15 mL). Subsequently, the aqueous phase was acidified using concd HCl and extracted with 10% iPrOH in CH2Cl2 (3×15 mL). The combined organic extract was dried over MgSO4 and concentrated under reduced pressure. The residue was washed with Et2O and dried under vacuum to afford the final product.

Reference： [1]Location in patent: experimental part Fang, Zhanxiong; Lam, Yulin [Tetrahedron, 2011, vol. 67, # 6, p. 1294 - 1297]

26
[ 109-57-9 ]
[ 328-42-7 ]
[ 66-99-9 ]
[ 1268854-70-1 ]

Yield	Reaction Conditions	Operation in experiment
79%	With trifluoroacetic acid In tetrahydrofuran at 95℃; for 0.25h; Microwave irradiation; Sealed tube; chemoselective reaction;	4.3. General procedure for the synthesis of 6m-6w General procedure: To a mixture of oxalacetic acid (2.6 mmol), aldehyde (2.0 mmol) and N-substituted urea/thiourea (2.6 mmol) in THF (3 mL) was added TFA (0.10 mL). The mixture was heated at 95 °C for 15 min using microwave irradiation in a sealed tube. Thereafter, the mixture was cooled and the solvent was removed under reduced pressure. 0.5 M NaOH (20 mL) was then added to the residue and the resulting solution was extracted with EtOAc (3×15 mL). Subsequently, the aqueous phase was acidified using concd HCl and extracted with 10% iPrOH in CH2Cl2 (3×15 mL). The combined organic extract was dried over MgSO4 and concentrated under reduced pressure. The residue was washed with Et2O and dried under vacuum to afford the final product.

Reference： [1]Location in patent: experimental part Fang, Zhanxiong; Lam, Yulin [Tetrahedron, 2011, vol. 67, # 6, p. 1294 - 1297]

27
[ 328-42-7 ]
[ 557-11-9 ]
[ 56990-02-4 ]
[ 1268854-75-6 ]

Yield	Reaction Conditions	Operation in experiment
77%	With trifluoroacetic acid; In tetrahydrofuran; at 95℃; for 0.25h;Microwave irradiation; Sealed tube;	General procedure: To a mixture of oxalacetic acid (2.6 mmol), aldehyde (2.0 mmol) and N-substituted urea/thiourea (2.6 mmol) in THF (3 mL) was added TFA (0.10 mL). The mixture was heated at 95 C for 15 min using microwave irradiation in a sealed tube. Thereafter, the mixture was cooled and the solvent was removed under reduced pressure. 0.5 M NaOH (20 mL) was then added to the residue and the resulting solution was extracted with EtOAc (3×15 mL). Subsequently, the aqueous phase was acidified using concd HCl and extracted with 10% iPrOH in CH2Cl2 (3×15 mL). The combined organic extract was dried over MgSO4 and concentrated under reduced pressure. The residue was washed with Et2O and dried under vacuum to afford the final product.

Reference： [1]Tetrahedron,2011,vol. 67,p. 1294 - 1297

28
[ 328-42-7 ]
[ 557-11-9 ]
[ 100-52-7 ]
[ 1268854-74-5 ]

Yield	Reaction Conditions	Operation in experiment
83%	With trifluoroacetic acid In tetrahydrofuran at 95℃; for 0.25h; Microwave irradiation; Sealed tube; chemoselective reaction;	4.3. General procedure for the synthesis of 6m-6w General procedure: To a mixture of oxalacetic acid (2.6 mmol), aldehyde (2.0 mmol) and N-substituted urea/thiourea (2.6 mmol) in THF (3 mL) was added TFA (0.10 mL). The mixture was heated at 95 °C for 15 min using microwave irradiation in a sealed tube. Thereafter, the mixture was cooled and the solvent was removed under reduced pressure. 0.5 M NaOH (20 mL) was then added to the residue and the resulting solution was extracted with EtOAc (3×15 mL). Subsequently, the aqueous phase was acidified using concd HCl and extracted with 10% iPrOH in CH2Cl2 (3×15 mL). The combined organic extract was dried over MgSO4 and concentrated under reduced pressure. The residue was washed with Et2O and dried under vacuum to afford the final product.

Reference： [1]Location in patent: experimental part Fang, Zhanxiong; Lam, Yulin [Tetrahedron, 2011, vol. 67, # 6, p. 1294 - 1297]

29
[ 328-42-7 ]
[ 557-11-9 ]
[ 66-99-9 ]
[ 1268854-76-7 ]

Yield	Reaction Conditions	Operation in experiment
81%	With trifluoroacetic acid In tetrahydrofuran at 95℃; for 0.25h; Microwave irradiation; Sealed tube; chemoselective reaction;	4.3. General procedure for the synthesis of 6m-6w General procedure: To a mixture of oxalacetic acid (2.6 mmol), aldehyde (2.0 mmol) and N-substituted urea/thiourea (2.6 mmol) in THF (3 mL) was added TFA (0.10 mL). The mixture was heated at 95 °C for 15 min using microwave irradiation in a sealed tube. Thereafter, the mixture was cooled and the solvent was removed under reduced pressure. 0.5 M NaOH (20 mL) was then added to the residue and the resulting solution was extracted with EtOAc (3×15 mL). Subsequently, the aqueous phase was acidified using concd HCl and extracted with 10% iPrOH in CH2Cl2 (3×15 mL). The combined organic extract was dried over MgSO4 and concentrated under reduced pressure. The residue was washed with Et2O and dried under vacuum to afford the final product.

Reference： [1]Location in patent: experimental part Fang, Zhanxiong; Lam, Yulin [Tetrahedron, 2011, vol. 67, # 6, p. 1294 - 1297]

30
[ 328-42-7 ]
[ 459-57-4 ]
[ 598-52-7 ]
[ 1268854-67-6 ]

Yield	Reaction Conditions	Operation in experiment
84%	With trifluoroacetic acid; In tetrahydrofuran; at 95℃; for 0.25h;Microwave irradiation; Sealed tube;	General procedure: To a mixture of oxalacetic acid (2.6 mmol), aldehyde (2.0 mmol) and N-substituted urea/thiourea (2.6 mmol) in THF (3 mL) was added TFA (0.10 mL). The mixture was heated at 95 C for 15 min using microwave irradiation in a sealed tube. Thereafter, the mixture was cooled and the solvent was removed under reduced pressure. 0.5 M NaOH (20 mL) was then added to the residue and the resulting solution was extracted with EtOAc (3×15 mL). Subsequently, the aqueous phase was acidified using concd HCl and extracted with 10% iPrOH in CH2Cl2 (3×15 mL). The combined organic extract was dried over MgSO4 and concentrated under reduced pressure. The residue was washed with Et2O and dried under vacuum to afford the final product.

Reference： [1]Tetrahedron,2011,vol. 67,p. 1294 - 1297

31
[ 328-42-7 ]
[ 459-57-4 ]
[ 17356-08-0 ]
[ 1268854-59-6 ]

Yield	Reaction Conditions	Operation in experiment
83%	With trifluoroacetic acid In tetrahydrofuran at 95℃; for 0.25h; Microwave irradiation; Sealed tube;	4.2. General procedure for the synthesis of 6a-6l General procedure: To a mixture of oxalacetic acid (2.6 mmol), aldehyde (2.0 mmol), and urea/thiourea (2.6 mmol) in THF (3 mL) was added TFA (0.10 mL). The mixture was heated at 95 °C for 15 min using microwave irradiation in a sealed tube. Thereafter, the mixture was cooled and the solvent was removed under reduced pressure. The residue obtained was washed with Et2O and dried under vacuum to afford the final product.

Reference： [1]Location in patent: experimental part Fang, Zhanxiong; Lam, Yulin [Tetrahedron, 2011, vol. 67, # 6, p. 1294 - 1297]

32
[ 328-42-7 ]
[ 459-57-4 ]
[ 57-13-6 ]
[ 721915-55-5 ]

Yield	Reaction Conditions	Operation in experiment
73%	With trifluoroacetic acid In tetrahydrofuran at 95℃; for 0.25h; Microwave irradiation; Sealed tube;	4.2. General procedure for the synthesis of 6a-6l General procedure: To a mixture of oxalacetic acid (2.6 mmol), aldehyde (2.0 mmol), and urea/thiourea (2.6 mmol) in THF (3 mL) was added TFA (0.10 mL). The mixture was heated at 95 °C for 15 min using microwave irradiation in a sealed tube. Thereafter, the mixture was cooled and the solvent was removed under reduced pressure. The residue obtained was washed with Et2O and dried under vacuum to afford the final product.

Reference： [1]Location in patent: experimental part Fang, Zhanxiong; Lam, Yulin [Tetrahedron, 2011, vol. 67, # 6, p. 1294 - 1297]

33
[ 328-42-7 ]
[ 459-57-4 ]
[ 598-50-5 ]
[ 1268854-72-3 ]

Yield	Reaction Conditions	Operation in experiment
83%	With trifluoroacetic acid In tetrahydrofuran at 95℃; for 0.25h; Microwave irradiation; Sealed tube; chemoselective reaction;	4.3. General procedure for the synthesis of 6m-6w General procedure: To a mixture of oxalacetic acid (2.6 mmol), aldehyde (2.0 mmol) and N-substituted urea/thiourea (2.6 mmol) in THF (3 mL) was added TFA (0.10 mL). The mixture was heated at 95 °C for 15 min using microwave irradiation in a sealed tube. Thereafter, the mixture was cooled and the solvent was removed under reduced pressure. 0.5 M NaOH (20 mL) was then added to the residue and the resulting solution was extracted with EtOAc (3×15 mL). Subsequently, the aqueous phase was acidified using concd HCl and extracted with 10% iPrOH in CH2Cl2 (3×15 mL). The combined organic extract was dried over MgSO4 and concentrated under reduced pressure. The residue was washed with Et2O and dried under vacuum to afford the final product.

Reference： [1]Location in patent: experimental part Fang, Zhanxiong; Lam, Yulin [Tetrahedron, 2011, vol. 67, # 6, p. 1294 - 1297]

34
[ 328-42-7 ]
[ 100-52-7 ]
[ 598-52-7 ]
[ 1268854-66-5 ]

Yield	Reaction Conditions	Operation in experiment
89%	With trifluoroacetic acid; In tetrahydrofuran; at 95℃; for 0.25h;Microwave irradiation; Sealed tube;	General procedure: To a mixture of oxalacetic acid (2.6 mmol), aldehyde (2.0 mmol) and N-substituted urea/thiourea (2.6 mmol) in THF (3 mL) was added TFA (0.10 mL). The mixture was heated at 95 C for 15 min using microwave irradiation in a sealed tube. Thereafter, the mixture was cooled and the solvent was removed under reduced pressure. 0.5 M NaOH (20 mL) was then added to the residue and the resulting solution was extracted with EtOAc (3×15 mL). Subsequently, the aqueous phase was acidified using concd HCl and extracted with 10% iPrOH in CH2Cl2 (3×15 mL). The combined organic extract was dried over MgSO4 and concentrated under reduced pressure. The residue was washed with Et2O and dried under vacuum to afford the final product.

Reference： [1]Tetrahedron,2011,vol. 67,p. 1294 - 1297

35
[ 328-42-7 ]
[ 100-52-7 ]
[ 17356-08-0 ]
[ 1268854-58-5 ]

Yield	Reaction Conditions	Operation in experiment
84%	With trifluoroacetic acid In 1,2-dichloro-ethane at 90℃; for 0.166667h; Microwave irradiation; Sealed tube;	4.2. General procedure for the synthesis of 6a-6l General procedure: To a mixture of oxalacetic acid (2.6 mmol), aldehyde (2.0 mmol), and urea/thiourea (2.6 mmol) in THF (3 mL) was added TFA (0.10 mL). The mixture was heated at 95 °C for 15 min using microwave irradiation in a sealed tube. Thereafter, the mixture was cooled and the solvent was removed under reduced pressure. The residue obtained was washed with Et2O and dried under vacuum to afford the final product.

Reference： [1]Location in patent: experimental part Fang, Zhanxiong; Lam, Yulin [Tetrahedron, 2011, vol. 67, # 6, p. 1294 - 1297]

36
[ 328-42-7 ]
[ 100-52-7 ]
[ 598-50-5 ]
[ 1268854-71-2 ]

Yield	Reaction Conditions	Operation in experiment
84%	With trifluoroacetic acid In tetrahydrofuran at 95℃; for 0.25h; Microwave irradiation; Sealed tube; chemoselective reaction;	4.3. General procedure for the synthesis of 6m-6w General procedure: To a mixture of oxalacetic acid (2.6 mmol), aldehyde (2.0 mmol) and N-substituted urea/thiourea (2.6 mmol) in THF (3 mL) was added TFA (0.10 mL). The mixture was heated at 95 °C for 15 min using microwave irradiation in a sealed tube. Thereafter, the mixture was cooled and the solvent was removed under reduced pressure. 0.5 M NaOH (20 mL) was then added to the residue and the resulting solution was extracted with EtOAc (3×15 mL). Subsequently, the aqueous phase was acidified using concd HCl and extracted with 10% iPrOH in CH2Cl2 (3×15 mL). The combined organic extract was dried over MgSO4 and concentrated under reduced pressure. The residue was washed with Et2O and dried under vacuum to afford the final product.

Reference： [1]Location in patent: experimental part Fang, Zhanxiong; Lam, Yulin [Tetrahedron, 2011, vol. 67, # 6, p. 1294 - 1297]

37
[ 328-42-7 ]
[ 66-99-9 ]
[ 17356-08-0 ]
[ 1268854-63-2 ]

Yield	Reaction Conditions	Operation in experiment
82%	With trifluoroacetic acid In tetrahydrofuran at 95℃; for 0.25h; Microwave irradiation; Sealed tube;	4.2. General procedure for the synthesis of 6a-6l General procedure: To a mixture of oxalacetic acid (2.6 mmol), aldehyde (2.0 mmol), and urea/thiourea (2.6 mmol) in THF (3 mL) was added TFA (0.10 mL). The mixture was heated at 95 °C for 15 min using microwave irradiation in a sealed tube. Thereafter, the mixture was cooled and the solvent was removed under reduced pressure. The residue obtained was washed with Et2O and dried under vacuum to afford the final product.

Reference： [1]Location in patent: experimental part Fang, Zhanxiong; Lam, Yulin [Tetrahedron, 2011, vol. 67, # 6, p. 1294 - 1297]

38
[ 328-42-7 ]
[ 66-99-9 ]
[ 57-13-6 ]
[ 908075-12-7 ]

Yield	Reaction Conditions	Operation in experiment
89%	With trifluoroacetic acid In tetrahydrofuran at 95℃; for 0.25h; Microwave irradiation; Sealed tube;	4.2. General procedure for the synthesis of 6a-6l General procedure: To a mixture of oxalacetic acid (2.6 mmol), aldehyde (2.0 mmol), and urea/thiourea (2.6 mmol) in THF (3 mL) was added TFA (0.10 mL). The mixture was heated at 95 °C for 15 min using microwave irradiation in a sealed tube. Thereafter, the mixture was cooled and the solvent was removed under reduced pressure. The residue obtained was washed with Et2O and dried under vacuum to afford the final product.

Reference： [1]Location in patent: experimental part Fang, Zhanxiong; Lam, Yulin [Tetrahedron, 2011, vol. 67, # 6, p. 1294 - 1297]

39
[ 328-42-7 ]
[ 17356-08-0 ]
[ 613-45-6 ]
[ 1268854-60-9 ]

Yield	Reaction Conditions	Operation in experiment
83%	With trifluoroacetic acid In tetrahydrofuran at 95℃; for 0.25h; Microwave irradiation; Sealed tube;	4.2. General procedure for the synthesis of 6a-6l General procedure: To a mixture of oxalacetic acid (2.6 mmol), aldehyde (2.0 mmol), and urea/thiourea (2.6 mmol) in THF (3 mL) was added TFA (0.10 mL). The mixture was heated at 95 °C for 15 min using microwave irradiation in a sealed tube. Thereafter, the mixture was cooled and the solvent was removed under reduced pressure. The residue obtained was washed with Et2O and dried under vacuum to afford the final product.

Reference： [1]Location in patent: experimental part Fang, Zhanxiong; Lam, Yulin [Tetrahedron, 2011, vol. 67, # 6, p. 1294 - 1297]

40
[ 328-42-7 ]
[ 613-45-6 ]
[ 57-13-6 ]
[ 1268854-64-3 ]

Yield	Reaction Conditions	Operation in experiment
91%	With trifluoroacetic acid In tetrahydrofuran at 95℃; for 0.25h; Microwave irradiation; Sealed tube;	4.2. General procedure for the synthesis of 6a-6l General procedure: To a mixture of oxalacetic acid (2.6 mmol), aldehyde (2.0 mmol), and urea/thiourea (2.6 mmol) in THF (3 mL) was added TFA (0.10 mL). The mixture was heated at 95 °C for 15 min using microwave irradiation in a sealed tube. Thereafter, the mixture was cooled and the solvent was removed under reduced pressure. The residue obtained was washed with Et2O and dried under vacuum to afford the final product.

Reference： [1]Location in patent: experimental part Fang, Zhanxiong; Lam, Yulin [Tetrahedron, 2011, vol. 67, # 6, p. 1294 - 1297]

41
[ 328-42-7 ]
[ 613-45-6 ]
[ 598-50-5 ]
[ 1268854-73-4 ]

Yield	Reaction Conditions	Operation in experiment
76%	With trifluoroacetic acid In tetrahydrofuran at 95℃; for 0.25h; Microwave irradiation; Sealed tube; chemoselective reaction;	4.3. General procedure for the synthesis of 6m-6w General procedure: To a mixture of oxalacetic acid (2.6 mmol), aldehyde (2.0 mmol) and N-substituted urea/thiourea (2.6 mmol) in THF (3 mL) was added TFA (0.10 mL). The mixture was heated at 95 °C for 15 min using microwave irradiation in a sealed tube. Thereafter, the mixture was cooled and the solvent was removed under reduced pressure. 0.5 M NaOH (20 mL) was then added to the residue and the resulting solution was extracted with EtOAc (3×15 mL). Subsequently, the aqueous phase was acidified using concd HCl and extracted with 10% iPrOH in CH2Cl2 (3×15 mL). The combined organic extract was dried over MgSO4 and concentrated under reduced pressure. The residue was washed with Et2O and dried under vacuum to afford the final product.

Reference： [1]Location in patent: experimental part Fang, Zhanxiong; Lam, Yulin [Tetrahedron, 2011, vol. 67, # 6, p. 1294 - 1297]

42
[ 328-42-7 ]
[ 2924-15-4 ]
[ 1318789-59-1 ]

Yield	Reaction Conditions	Operation in experiment
90%	With sulfuric acid; In water; for 2.41667h;	Synthesis example 11 -(2-Fluoro-phenyl)-5-hydroxy-1 H-pyrazole-3-carboxylic acidSulfuric acid (400 ml) was added slowly to water (400 ml). After cooling to 5 C,2-fluoro-phenylhydrazine hydrochloride (123 g, 757 mmol) was added resulting in a brown suspension. Then a solution of oxalacetic acid (100 g, 757 mmol) in water (400 ml) was added slowly during a period of 25 min. After 2 h the conversion was complete and the solid was filtered. After washing with water the solid was dried. The product was obtained as light brown solid (151 g, 90 %).

Reference： [1]Patent: WO2011/92187,2011,A1 .Location in patent: Page/Page column 107
[2]Journal of Medicinal Chemistry,2012,vol. 55,p. 7636 - 7649

43
[ 328-42-7 ]
[ 658-27-5 ]
[ 1163791-71-6 ]

Reference： [1]Journal of Medicinal Chemistry,2012,vol. 55,p. 7636 - 7649

44
[ 636-61-3 ]
[ 328-42-7 ]

Yield	Reaction Conditions	Operation in experiment
	With recombinant D-lactate dehydrogenase from Lactobacillus jensenii 269-3; nicotinamide adenine dinucleotide In aq. phosphate buffer at 25℃; Enzymatic reaction;	Substrate specificity of d-LDHs General procedure: Substrate specificities of d-LDHs were examined using 50 mM sodium phosphatebuffer (pH 8.0) containing 10 mM various substrates (sodium pyruvate,2-ketobutyric acid, oxaloacetic acid, sodium phenylpyruvate) for reduction reactionand 10 mM various substrates (sodium d-lactate, (R)-2-hydroxybutyric acid,d-(+)-malic acid, d-(+)-3-phenyllactic acid) for oxidation reaction.

Reference： [1]Jun, Chanha; Sa, Young Seung; Gu, Sol-A; Joo, Jeong Chan; Kim, Seil; Kim, Kyung-Jin; Kim, Yong Hwan [Process Biochemistry, 2013, vol. 48, # 1, p. 109 - 117]

45
[ 328-42-7 ]
[ 636-61-3 ]

Yield	Reaction Conditions	Operation in experiment
	With recombinant D-lactate dehydrogenase from Lactobacillus jensenii 27-2 CHN; NADH In aq. phosphate buffer at 25℃; Enzymatic reaction;	Substrate specificity of d-LDHs General procedure: Substrate specificities of d-LDHs were examined using 50 mM sodium phosphatebuffer (pH 8.0) containing 10 mM various substrates (sodium pyruvate,2-ketobutyric acid, oxaloacetic acid, sodium phenylpyruvate) for reduction reactionand 10 mM various substrates (sodium d-lactate, (R)-2-hydroxybutyric acid,d-(+)-malic acid, d-(+)-3-phenyllactic acid) for oxidation reaction.

Reference： [1]Jun, Chanha; Sa, Young Seung; Gu, Sol-A; Joo, Jeong Chan; Kim, Seil; Kim, Kyung-Jin; Kim, Yong Hwan [Process Biochemistry, 2013, vol. 48, # 1, p. 109 - 117]

46
[ 328-42-7 ]
[ 338-69-2 ]
[ 1783-96-6 ]
[ 127-17-3 ]

Yield	Reaction Conditions	Operation in experiment
	With pyridoxal 5'-phosphate; recombinant Lactobacillus salivarius UCC118 D-amino acid aminotransferase; In aq. phosphate buffer; at 30℃; for 0.0166667h;pH 7.5;Enzymatic reaction;	General procedure: Amino acceptor specificity was determined using a modification of the salicylaldehyde method by measuring the rate of pyruvate formation from D-alanine in the presence of an alpha-keto acid. The standard reaction mixture contained 100 mM potassium phosphate buffer (pH 7.5), 50 mM D-alanine, 20 mM alpha-keto acid, 0.05 mM pyridoxal-5?-phosphate and purified D-AAT. The reaction was run at 30 C for 1 min in a total volume of 1 ml, and the reaction was stopped by adding 1 ml of 60% potassium hydroxide, after which 0.5 ml of 2% salicylaldehyde dissolved in 99% ethanol was added, and the mixture was incubated for 30 min at 30 C. Thereafter, 1.5 ml of cold distilled water was added to the orange colored reaction mixture and absorbance at 480 nm was measured. The reaction mixture was also incubated for 1 min without the purified enzyme. The enzyme concentration was determined using the Bradford method with Bio-Rad Protein Assay Dye Reagent Concentrate (Bio-Rad, CA, USA). All enzyme assays were performed more than 3 times.

Reference： [1]Journal of Molecular Catalysis B: Enzymatic,2013,vol. 94,p. 15 - 22

47
[ 211915-06-9 ]
[ 328-42-7 ]
C₃₄H₄₁N₇O₅*C₄H₄O₅ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
98.8%	In trifluoroacetic acid at 30℃; for 6h;	1 Embodiment 5 The embodiment uses the darbey adds the group ester of the invention is the preparation of salts Oxaloacetae.The 1.6mmol the darbey adds the group ester and 3.2mmol in Oxaloacetae of 10 °C the 20 ml acetone, mixing and stirring 6 hours into a salt, then the 10 °C lower crystallization, filtration, washed with ether, dried, adding acetone recrystallization, get 0.452g the darbey adds the group ester Oxaloacetae salt of acetone solvate. Measure its ESI-MS(m/z): 789 [M+H]+.The acetone solvate thereof for drying, to obtain white solid darbey adds the group esteroxyl acetate 0.435g, by calculating, in the above-mentioned solvent compound, darbey adds the group ester Oxaloacetae the content of the salt is 96.3 wt %. Each molecule in the acetone solvate containing 0.5 molecule of acetone.

Reference： [1]Current Patent Assignee: TIANJIN INSTITUTE OF PHARMACEUTICAL RESEARCH - CN105348259, 2016, A Location in patent: Paragraph 0115-0127

48
[ 211915-06-9 ]
[ 328-42-7 ]
C₃₄H₄₁N₇O₅*0.5C₄H₄O₅ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
97.5%	In ethanol at 30℃; for 6h;	2 Embodiment 2 The embodiment uses the darbey adds the group ester of the invention is the preparation of salts Oxaloacetae.The 3.2mmol the darbey adds the group ester and 1.6mmol in Oxaloacetae of 30 °C the 20 ml water, mixing and stirring 6 hours into a salt, then the 30 °C lower crystallization, filtration, washing with ethyl acetate, dried, adding water recrystallization, get 0.446g the darbey adds the group ester Oxaloacetae salt hydrate. Measured ESI-MS(m/z): 712 [M+H]+.To the above hydrate is dried, to obtain white solid darbey adds the group esteroxyl acetate 0.435g, by calculating, in the above-mentioned hydrate, darbey adds the group ester Oxaloacetae salt is in a content of 97.5 wt %. In each molecule of the hydrate containing 1 molecule of water, i.e. a water composition.

Reference： [1]Current Patent Assignee: TIANJIN INSTITUTE OF PHARMACEUTICAL RESEARCH - CN105348259, 2016, A Location in patent: Paragraph 0062-0075

49
[ 328-42-7 ]
[ 2863-98-1 ]
1-(4-cyanophenyl)-5-hydroxy-pyrazole-3-carboxylic acid [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
93%	In acetic acid for 1h; Reflux;	1-(4-Cyanophenyl)-5-hydroxy-pyrazole-3-carboxylic acid9, A suspension of oxaloacetic acid (780 mg, 5.9 mmol) and 4-cyanophenylhydrazine hydrochloride (1 g, 5.9 mmol) in acetic acid (15 mL) was heated to reflux for 1 h. The reaction mixture was cooled to room temperature, and then water (20 mL) was added. The resulting white precipitate was collected by filtration and dried to afford the title compound (1.26 g, 93%) as a white powder.1H NMR (300 MHz, DMSO-d6) δ 12.63 (br s, 1H), 12.32 (br s, 1H), 8.11-7.89 (m, 4H), 5.95 (s, 1H). LC-MS: (Low pH) tR0.71 min,m/z228.1 [M-H]-, 100% purity.

Reference： [1]Mould, Daniel P.; Bremberg, Ulf; Jordan, Allan M.; Geitmann, Matthis; Maiques-Diaz, Alba; McGonagle, Alison E.; Small, Helen F.; Somervaille, Tim C.P.; Ogilvie, Donald [Bioorganic and Medicinal Chemistry Letters, 2017, vol. 27, # 14, p. 3190 - 3195]

50
[ 328-42-7 ]
[ 10323-20-3 ]
[ 76249-76-8 ]

Yield	Reaction Conditions	Operation in experiment
	Stage #1: Oxalacetic acid; D-Arabinose With sodium hydroxide In water at 20℃; for 3h; Inert atmosphere; Stage #2: With nickel(II) chloride hexahydrate; acetic acid In water at 60℃; for 2h; Inert atmosphere; Further stages;	2.1. Synthesis of ethyl (acetyl 4,5,7,8-tetra-O-acetyl-3-deoxy-α-D-mannooct-2-ulopyranoside)onate 3 In a glass beaker, 200 ml of ice-water was adjusted to pH 10 by addition of 10 M aq. NaOH. With constant stirring, oxalacetic acid 2 (25 g, 189.3 mmol) and 10 M aq.NaOH were added to keep the pH as close to 10 as possible. Then D-arabinose 1 (77 g, 513.3 mmol) was added in one portion and the pH was immediately adjusted to 11 by addition of 10 M aq. NaOH and kept at room temperature for 3 h. The pH of the reaction mixture was lowered to 7 by addition of Amberlite IR120 H+ resin. The resin was removed by filtration, and the pH was adjusted to 5 by addition of acetic acid and a catalytic amount of NiCl2*6H2O (150 mg, 1.2 mmol). The mixture was heated to 60 °C and stirred for 2 h. After cooling to room temperature, the product solution was subjected to a DOWEX 1×8 column loaded with HCO3-. The column was washed with water (600 ml) to remove unreacted D-arabinose, followed by a step gradient of ammonium bicarbonate buffer (100 ml H2O - n × 10 ml H2O + n × 10 ml 0.5 M NH4HCO3, n = 1 - 10) to collect the kdo-containing fractions. The kdo-containing fractions were concentrated in vacuo to give the crude Kdo (17 g) as a pale yellow solid for the next step without further purification.

Reference： [1]Mi, Xuemeng; Lou, Qixin; Fan, Wenjing; Zhuang, Liqin; Yang, You [Carbohydrate Research, 2017, vol. 448, p. 161 - 165]

51
[ 77287-34-4 ]
[ 51953-18-5 ]
[ 1455-77-2 ]
[ 120-89-8 ]
[ 849585-22-4 ]
[ 73-40-5 ]
[ 328-42-7 ]
[ 2491-15-8 ]
[ 110-15-6 ]
[ 71-30-7 ]
[ 120-73-0 ]
[ 144-62-7 ]
[ 113-00-8 ]
[ 127-17-3 ]
[ 66-22-8 ]
[ 56-06-4 ]
[ 66224-66-6 ]
[ 57-13-6 ]
[ 56-40-6 ]
[ 302-72-7 ]
[ 18588-61-9 ]
isocytosine [ No CAS ]

Reference： [1]Chemistry - A European Journal,2018,vol. 24,p. 8126 - 8132

52
[ 77287-34-4 ]
[ 51953-18-5 ]
[ 120-89-8 ]
[ 849585-22-4 ]
[ 73-40-5 ]
[ 328-42-7 ]
[ 2491-15-8 ]
[ 110-15-6 ]
[ 71-30-7 ]
[ 144-62-7 ]
[ 113-00-8 ]
[ 127-17-3 ]
[ 66-22-8 ]
[ 66224-66-6 ]
[ 56-40-6 ]
[ 18588-61-9 ]
isocytosine [ No CAS ]
[ 18514-52-8 ]

Reference： [1]Chemistry - A European Journal,2018,vol. 24,p. 8126 - 8132

53
[ 77287-34-4 ]
[ 51953-18-5 ]
[ 1455-77-2 ]
[ 120-89-8 ]
[ 73-40-5 ]
[ 328-42-7 ]
[ 2491-15-8 ]
[ 110-15-6 ]
[³H]-hypoxanthine [ No CAS ]
[ 71-30-7 ]
[ 120-73-0 ]
[ 144-62-7 ]
[ 113-00-8 ]
[ 127-17-3 ]
[ 66-22-8 ]
[ 66224-66-6 ]
[ 57-13-6 ]
[ 56-40-6 ]
[ 302-72-7 ]
isocytosine [ No CAS ]

Reference： [1]Chemistry - A European Journal,2018,vol. 24,p. 8126 - 8132

54
[ 77287-34-4 ]
[ 23147-58-2 ]
[ 1455-77-2 ]
[ 849585-22-4 ]
[ 328-42-7 ]
[ 110-15-6 ]
[ 120-73-0 ]
[ 144-62-7 ]
[ 66-22-8 ]
[ 56-06-4 ]
[ 57-13-6 ]

Reference： [1]Chemistry - A European Journal,2018,vol. 24,p. 8126 - 8132

55
[ 77287-34-4 ]
[ 51953-18-5 ]
[ 120-89-8 ]
[ 73-40-5 ]
[ 328-42-7 ]
[ 110-15-6 ]
[ 144-62-7 ]
[ 127-17-3 ]
[ 56-06-4 ]
[ 57-13-6 ]
[ 18588-61-9 ]
[ 18514-52-8 ]

Reference： [1]Chemistry - A European Journal,2018,vol. 24,p. 8126 - 8132

56
[ 77287-34-4 ]
[ 849585-22-4 ]
[ 328-42-7 ]
[ 120-73-0 ]
[ 144-62-7 ]
[ 127-17-3 ]

Reference： [1]Chemistry - A European Journal,2018,vol. 24,p. 8126 - 8132

57
[ 328-42-7 ]
C₄H₂Cl₂O₃ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With oxalyl dichloride; N,N-dimethyl-formamide In dichloromethane at 20℃; for 2h;	1 General Procedure for the Synthesis of OAA(BHB)₂ and OAA(PG)₂: OAA (1 equivalent) was dissolved in anhydrous dichloromethane (DCM) (0.1 M based off OAA) with a catalytic amount of dimethylformamide (DMF) (~l drop). Oxalyl chloride (2.5 equivalents) was added dropwise and the reaction was stirred at room temperature for 2 hours. The vial was evaporated to dryness to yield a yellow oil containing the diacyl chloride of OAA. In a separate vial, 2 equivalents of the appropriate alcohol (3 -hydroxy butanoic acid if synthesizing OAA(BHB)2 or propane- 1 ,2-diol if synthesizing OAAfPGf ) and NaH (2 equivalents) were suspended in DCM and stirred for 30 minutes. The diacyl chloride of OAA was redissolved in DCM and DMF and added dropwise to the vial containing the alcohol and NaH. The reaction was left to stir overnight, after which the solvent was evaporated to obtain the product.

Reference： [1]Current Patent Assignee: UNIVERSITY OF KANSAS - WO2020/69527, 2020, A1 Location in patent: Paragraph 0075-0076; 0079

58
[ 328-42-7 ]
[ 95-54-5 ]
[ 939-70-8 ]

Yield	Reaction Conditions	Operation in experiment
76%	With hydrogenchloride In methanol at 75℃; for 16h;	1.57.1 Step 1 1,2-Benzenediamine (2.00 g; 18.49 mmol; 1.00 eq.) and 2-oxobutanedioic acid (2.44 g; 18.49 mmol; 1.00 eq.) were suspended in methanol (20 ml). 4 M HCl (4.6 ml) was added and a thick mixture formed. The mixture was stirred in a heat block at 75° C. for 16 h. The reaction was evaporated and taken up in ethyl acetate (100 ml) and sodium bicarbonate solution (50 ml). Some insoluble solids were filtered off, rinsed with ethyl acetate, and retained as product. The phases were separated, and the aqueous phase was extracted with more ethyl acetate (50 ml). The combined organic phases were dried over sodium sulfate, evaporated, and purified by silica gel chromatography (ethyl acetate/hexanes gradient). Purified fractions were combined with the previously retained solids to give an off-white solid of 1-(1H-benzimidazol-2-yl)ethenone (2.26 g, 76%). MS (ES+): (M+H)+=160.5. 1H NMR (400 MHz, DMSO-d6) δ 12.29 (s, 1H), 7.69 (dd, J=7.6, 1.2 Hz, 1H), 7.46 (ddd, J=8.4, 7.2, 1.5 Hz, 1H), 7.31-7.22 (m, 2H), 2.40 (s, 3H).

Reference： [1]Current Patent Assignee: GLOBAL BLOOD THERAPEUTICS, INC. - US2020/190045, 2020, A1 Location in patent: Paragraph 0557; 0558

59
[ 880-09-1 ]
[ 328-42-7 ]
C₉H₁₅NO₃ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
1.2 g	With acetic acid In ethanol at 69℃; for 2h;	4.1 1^st Step: Synthesis of the Intermediate (IV) In a 10 mL reactor under argon equipped with a temperature probe, are introduced successively at C. 500 mg of oxaloacetic acid 10-5 mL of EtOH 209 mg of acetic acid After dissolution of the acid (about 5 minutes of stirring), dipiperidinomethane (0.95 eq.) is added in 50 minutes via a syringe pump. After the end of the addition, the medium is heated to 60° C. in 1 hour then stirred at this 15 temperature for 10 minutes. A control by HPLC-MS (ESI+) confirms the formation of the intermediate IV.

Reference： [1]Current Patent Assignee: SINOCHEM HOLDINGS CORPORATION LTD - US2020/283387, 2020, A1 Location in patent: Paragraph 0085-0095

60
[ 328-42-7 ]
[ 5188-07-8 ]
[ 51828-97-8 ]

Yield	Reaction Conditions	Operation in experiment
	Stage #1: Oxalacetic acid With sodium hydroxide In water at 30℃; for 0.0333333h; Stage #2: With formaldehyd In water at 30℃; for 0.0333333h; Stage #3: sodium thiomethoxide In water at 30℃; for 0.5h;	1 EXAMPLE 1: PREPARATION OF KMB BY THE FIRST ROUTE IN THE PRESENCE OF NAOH, HCHO AND MESNA In a reactor, 100 mg of oxaloacetic acid are placed and a solution of NaOH 1 M is added (2 eq.). The reactor is placed at 30° C. and the dissolution of the oxaloacetic acid is immediate. After 2 minutes, the 37% w/w formaldehyde solution is added (1 eq). The stirring is maintained for 2 minutes at 30° C. then the MeSNa (2 eq., 108 mg) is added in one portion and the reaction medium is stirred at 30° C. (0053) A monitoring of the reaction by HPLC-UV (column C18 Hydro-RP) is performed after 10 minutes of contact then every 20 minutes. The best performances were measured after 30 minutes of contact at 30° C. with the following results: (0054) Conversionoxaloacetic acid=100% (0055) Dosed yield in KMB=75% (0056) Selectivity in KMB=75%

Reference： [1]Current Patent Assignee: SINOCHEM HOLDINGS CORPORATION LTD - US2020/283387, 2020, A1 Location in patent: Paragraph 0051-0056

61
[ 328-42-7 ]
[ 64-17-5 ]
[ 19501-58-7 ]
ethyl 5-hydroxy-1-(4-methoxyphenyl)-1H-pyrazole-3-carboxylate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
67.6%	at 85℃; for 12h;	4.1.1. 5-methyl-1-(4-((N-methylsulfiiamoyl)methyl)phenyl)-1H-pyrazole-3-carboxylic acid (12a) General procedure: Step 2. To a solution of 8a (118 mg, 1 mmol) and 4-hydrazino-N-methylbenzenemethanesulfonamide hydrochloride (9, 252 mg, 1 mmol) in anhydrous ethanol (10 mL) was stirred at 85 °C overnight. The reaction was allowed to cool to room temperature and concentrated. The crude material was purified by Isolera Biotage LPLC (PE/EA = 30%) to give a mixture of methyl 5-methyl-1-(4-((N-methylsulflamoyl)methyl)phenyl)-1H-pyrazole-3-carboxylate (10a) and ethyl 5-methyl-1-(4-((N-methylsulflamoyl)methyl)phenyl)-1H-pyrazole-3-carboxylate (11a) as a white solid.
67.6%	at 85℃; for 12h;	4.1.1. 5-methyl-1-(4-((N-methylsulfiiamoyl)methyl)phenyl)-1H-pyrazole-3-carboxylic acid (12a) General procedure: Step 2. To a solution of 8a (118 mg, 1 mmol) and 4-hydrazino-N-methylbenzenemethanesulfonamide hydrochloride (9, 252 mg, 1 mmol) in anhydrous ethanol (10 mL) was stirred at 85 °C overnight. The reaction was allowed to cool to room temperature and concentrated. The crude material was purified by Isolera Biotage LPLC (PE/EA = 30%) to give a mixture of methyl 5-methyl-1-(4-((N-methylsulflamoyl)methyl)phenyl)-1H-pyrazole-3-carboxylate (10a) and ethyl 5-methyl-1-(4-((N-methylsulflamoyl)methyl)phenyl)-1H-pyrazole-3-carboxylate (11a) as a white solid.

Reference： [1]Fan, Yan; Fang, Zhen; Guo, Nihong; Guo, Yinping; Li, Linli; Liu, Yang; Mu, Bo; Xia, Anjie; Xiang, Rong; Xiong, Liang; Yang, Shengyong; Yao, Rui; Zhang, Hailin; Zhang, Rong [European Journal of Medicinal Chemistry, 2022, vol. 238]
[2]Fan, Yan; Fang, Zhen; Guo, Nihong; Guo, Yinping; Li, Linli; Liu, Yang; Mu, Bo; Xia, Anjie; Xiang, Rong; Xiong, Liang; Yang, Shengyong; Yao, Rui; Zhang, Hailin; Zhang, Rong [European Journal of Medicinal Chemistry, 2022, vol. 238]

62
[ 328-42-7 ]
[ 64-17-5 ]
[ 17852-67-4 ]
ethyl 5-hydroxy-1-(4-(methylsulfonyl)phenyl)-1H-pyrazole-3-carboxylate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
58.7%	at 85℃; for 12h;	4.1.1. 5-methyl-1-(4-((N-methylsulfiiamoyl)methyl)phenyl)-1H-pyrazole-3-carboxylic acid (12a) General procedure: Step 2. To a solution of 8a (118 mg, 1 mmol) and 4-hydrazino-N-methylbenzenemethanesulfonamide hydrochloride (9, 252 mg, 1 mmol) in anhydrous ethanol (10 mL) was stirred at 85 °C overnight. The reaction was allowed to cool to room temperature and concentrated. The crude material was purified by Isolera Biotage LPLC (PE/EA = 30%) to give a mixture of methyl 5-methyl-1-(4-((N-methylsulflamoyl)methyl)phenyl)-1H-pyrazole-3-carboxylate (10a) and ethyl 5-methyl-1-(4-((N-methylsulflamoyl)methyl)phenyl)-1H-pyrazole-3-carboxylate (11a) as a white solid.
58.7%	at 85℃; for 12h;	4.1.1. 5-methyl-1-(4-((N-methylsulfiiamoyl)methyl)phenyl)-1H-pyrazole-3-carboxylic acid (12a) General procedure: Step 2. To a solution of 8a (118 mg, 1 mmol) and 4-hydrazino-N-methylbenzenemethanesulfonamide hydrochloride (9, 252 mg, 1 mmol) in anhydrous ethanol (10 mL) was stirred at 85 °C overnight. The reaction was allowed to cool to room temperature and concentrated. The crude material was purified by Isolera Biotage LPLC (PE/EA = 30%) to give a mixture of methyl 5-methyl-1-(4-((N-methylsulflamoyl)methyl)phenyl)-1H-pyrazole-3-carboxylate (10a) and ethyl 5-methyl-1-(4-((N-methylsulflamoyl)methyl)phenyl)-1H-pyrazole-3-carboxylate (11a) as a white solid.

Reference： [1]Fan, Yan; Fang, Zhen; Guo, Nihong; Guo, Yinping; Li, Linli; Liu, Yang; Mu, Bo; Xia, Anjie; Xiang, Rong; Xiong, Liang; Yang, Shengyong; Yao, Rui; Zhang, Hailin; Zhang, Rong [European Journal of Medicinal Chemistry, 2022, vol. 238]
[2]Fan, Yan; Fang, Zhen; Guo, Nihong; Guo, Yinping; Li, Linli; Liu, Yang; Mu, Bo; Xia, Anjie; Xiang, Rong; Xiong, Liang; Yang, Shengyong; Yao, Rui; Zhang, Hailin; Zhang, Rong [European Journal of Medicinal Chemistry, 2022, vol. 238]

63
[ 328-42-7 ]
[ 64-17-5 ]
[ 118427-29-5 ]
ethyl 5-hydroxy-1-(4-isopropylphenyl)-1H-pyrazole-3-carboxylate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
84.3%	at 85℃; for 12h;	4.1.1. 5-methyl-1-(4-((N-methylsulfiiamoyl)methyl)phenyl)-1H-pyrazole-3-carboxylic acid (12a) General procedure: Step 2. To a solution of 8a (118 mg, 1 mmol) and 4-hydrazino-N-methylbenzenemethanesulfonamide hydrochloride (9, 252 mg, 1 mmol) in anhydrous ethanol (10 mL) was stirred at 85 °C overnight. The reaction was allowed to cool to room temperature and concentrated. The crude material was purified by Isolera Biotage LPLC (PE/EA = 30%) to give a mixture of methyl 5-methyl-1-(4-((N-methylsulflamoyl)methyl)phenyl)-1H-pyrazole-3-carboxylate (10a) and ethyl 5-methyl-1-(4-((N-methylsulflamoyl)methyl)phenyl)-1H-pyrazole-3-carboxylate (11a) as a white solid.
84.3%	at 85℃; for 12h;	4.1.1. 5-methyl-1-(4-((N-methylsulfiiamoyl)methyl)phenyl)-1H-pyrazole-3-carboxylic acid (12a) General procedure: Step 2. To a solution of 8a (118 mg, 1 mmol) and 4-hydrazino-N-methylbenzenemethanesulfonamide hydrochloride (9, 252 mg, 1 mmol) in anhydrous ethanol (10 mL) was stirred at 85 °C overnight. The reaction was allowed to cool to room temperature and concentrated. The crude material was purified by Isolera Biotage LPLC (PE/EA = 30%) to give a mixture of methyl 5-methyl-1-(4-((N-methylsulflamoyl)methyl)phenyl)-1H-pyrazole-3-carboxylate (10a) and ethyl 5-methyl-1-(4-((N-methylsulflamoyl)methyl)phenyl)-1H-pyrazole-3-carboxylate (11a) as a white solid.

Reference： [1]Fan, Yan; Fang, Zhen; Guo, Nihong; Guo, Yinping; Li, Linli; Liu, Yang; Mu, Bo; Xia, Anjie; Xiang, Rong; Xiong, Liang; Yang, Shengyong; Yao, Rui; Zhang, Hailin; Zhang, Rong [European Journal of Medicinal Chemistry, 2022, vol. 238]
[2]Fan, Yan; Fang, Zhen; Guo, Nihong; Guo, Yinping; Li, Linli; Liu, Yang; Mu, Bo; Xia, Anjie; Xiang, Rong; Xiong, Liang; Yang, Shengyong; Yao, Rui; Zhang, Hailin; Zhang, Rong [European Journal of Medicinal Chemistry, 2022, vol. 238]

64
[ 328-42-7 ]
[ 64-17-5 ]
[ 13957-54-5 ]
ethyl 5-hydroxy-1-(4-(trifluoromethoxy)phenyl)-1H-pyrazole-3-carboxylic acid [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
59.4%	at 85℃; for 12h;	4.1.1. 5-methyl-1-(4-((N-methylsulfiiamoyl)methyl)phenyl)-1H-pyrazole-3-carboxylic acid (12a) General procedure: Step 2. To a solution of 8a (118 mg, 1 mmol) and 4-hydrazino-N-methylbenzenemethanesulfonamide hydrochloride (9, 252 mg, 1 mmol) in anhydrous ethanol (10 mL) was stirred at 85 °C overnight. The reaction was allowed to cool to room temperature and concentrated. The crude material was purified by Isolera Biotage LPLC (PE/EA = 30%) to give a mixture of methyl 5-methyl-1-(4-((N-methylsulflamoyl)methyl)phenyl)-1H-pyrazole-3-carboxylate (10a) and ethyl 5-methyl-1-(4-((N-methylsulflamoyl)methyl)phenyl)-1H-pyrazole-3-carboxylate (11a) as a white solid.
59.4%	at 85℃; for 12h;	4.1.1. 5-methyl-1-(4-((N-methylsulfiiamoyl)methyl)phenyl)-1H-pyrazole-3-carboxylic acid (12a) General procedure: Step 2. To a solution of 8a (118 mg, 1 mmol) and 4-hydrazino-N-methylbenzenemethanesulfonamide hydrochloride (9, 252 mg, 1 mmol) in anhydrous ethanol (10 mL) was stirred at 85 °C overnight. The reaction was allowed to cool to room temperature and concentrated. The crude material was purified by Isolera Biotage LPLC (PE/EA = 30%) to give a mixture of methyl 5-methyl-1-(4-((N-methylsulflamoyl)methyl)phenyl)-1H-pyrazole-3-carboxylate (10a) and ethyl 5-methyl-1-(4-((N-methylsulflamoyl)methyl)phenyl)-1H-pyrazole-3-carboxylate (11a) as a white solid.

Reference： [1]Fan, Yan; Fang, Zhen; Guo, Nihong; Guo, Yinping; Li, Linli; Liu, Yang; Mu, Bo; Xia, Anjie; Xiang, Rong; Xiong, Liang; Yang, Shengyong; Yao, Rui; Zhang, Hailin; Zhang, Rong [European Journal of Medicinal Chemistry, 2022, vol. 238]
[2]Fan, Yan; Fang, Zhen; Guo, Nihong; Guo, Yinping; Li, Linli; Liu, Yang; Mu, Bo; Xia, Anjie; Xiang, Rong; Xiong, Liang; Yang, Shengyong; Yao, Rui; Zhang, Hailin; Zhang, Rong [European Journal of Medicinal Chemistry, 2022, vol. 238]

65
[ 328-42-7 ]
[ 64-17-5 ]
[ 27246-81-7 ]
[ 64919-91-1 ]

Yield	Reaction Conditions	Operation in experiment
65%	at 85℃; for 12h;	4.1.1. 5-methyl-1-(4-((N-methylsulfiiamoyl)methyl)phenyl)-1H-pyrazole-3-carboxylic acid (12a) General procedure: Step 2. To a solution of 8a (118 mg, 1 mmol) and 4-hydrazino-N-methylbenzenemethanesulfonamide hydrochloride (9, 252 mg, 1 mmol) in anhydrous ethanol (10 mL) was stirred at 85 °C overnight. The reaction was allowed to cool to room temperature and concentrated. The crude material was purified by Isolera Biotage LPLC (PE/EA = 30%) to give a mixture of methyl 5-methyl-1-(4-((N-methylsulflamoyl)methyl)phenyl)-1H-pyrazole-3-carboxylate (10a) and ethyl 5-methyl-1-(4-((N-methylsulflamoyl)methyl)phenyl)-1H-pyrazole-3-carboxylate (11a) as a white solid.
65%	at 85℃; for 12h;	4.1.1. 5-methyl-1-(4-((N-methylsulfiiamoyl)methyl)phenyl)-1H-pyrazole-3-carboxylic acid (12a) General procedure: Step 2. To a solution of 8a (118 mg, 1 mmol) and 4-hydrazino-N-methylbenzenemethanesulfonamide hydrochloride (9, 252 mg, 1 mmol) in anhydrous ethanol (10 mL) was stirred at 85 °C overnight. The reaction was allowed to cool to room temperature and concentrated. The crude material was purified by Isolera Biotage LPLC (PE/EA = 30%) to give a mixture of methyl 5-methyl-1-(4-((N-methylsulflamoyl)methyl)phenyl)-1H-pyrazole-3-carboxylate (10a) and ethyl 5-methyl-1-(4-((N-methylsulflamoyl)methyl)phenyl)-1H-pyrazole-3-carboxylate (11a) as a white solid.

Reference： [1]Fan, Yan; Fang, Zhen; Guo, Nihong; Guo, Yinping; Li, Linli; Liu, Yang; Mu, Bo; Xia, Anjie; Xiang, Rong; Xiong, Liang; Yang, Shengyong; Yao, Rui; Zhang, Hailin; Zhang, Rong [European Journal of Medicinal Chemistry, 2022, vol. 238]
[2]Fan, Yan; Fang, Zhen; Guo, Nihong; Guo, Yinping; Li, Linli; Liu, Yang; Mu, Bo; Xia, Anjie; Xiang, Rong; Xiong, Liang; Yang, Shengyong; Yao, Rui; Zhang, Hailin; Zhang, Rong [European Journal of Medicinal Chemistry, 2022, vol. 238]

66
[ 328-42-7 ]
[ 64-17-5 ]
α,α,α-trifluoro-3-tolylhydrazine hydrochloride [ No CAS ]
[ 64919-90-0 ]

Yield	Reaction Conditions	Operation in experiment
86.3%	at 85℃; for 12h;	4.1.1. 5-methyl-1-(4-((N-methylsulfiiamoyl)methyl)phenyl)-1H-pyrazole-3-carboxylic acid (12a) General procedure: Step 2. To a solution of 8a (118 mg, 1 mmol) and 4-hydrazino-N-methylbenzenemethanesulfonamide hydrochloride (9, 252 mg, 1 mmol) in anhydrous ethanol (10 mL) was stirred at 85 °C overnight. The reaction was allowed to cool to room temperature and concentrated. The crude material was purified by Isolera Biotage LPLC (PE/EA = 30%) to give a mixture of methyl 5-methyl-1-(4-((N-methylsulflamoyl)methyl)phenyl)-1H-pyrazole-3-carboxylate (10a) and ethyl 5-methyl-1-(4-((N-methylsulflamoyl)methyl)phenyl)-1H-pyrazole-3-carboxylate (11a) as a white solid.
86.3%	at 85℃; for 12h;	4.1.1. 5-methyl-1-(4-((N-methylsulfiiamoyl)methyl)phenyl)-1H-pyrazole-3-carboxylic acid (12a) General procedure: Step 2. To a solution of 8a (118 mg, 1 mmol) and 4-hydrazino-N-methylbenzenemethanesulfonamide hydrochloride (9, 252 mg, 1 mmol) in anhydrous ethanol (10 mL) was stirred at 85 °C overnight. The reaction was allowed to cool to room temperature and concentrated. The crude material was purified by Isolera Biotage LPLC (PE/EA = 30%) to give a mixture of methyl 5-methyl-1-(4-((N-methylsulflamoyl)methyl)phenyl)-1H-pyrazole-3-carboxylate (10a) and ethyl 5-methyl-1-(4-((N-methylsulflamoyl)methyl)phenyl)-1H-pyrazole-3-carboxylate (11a) as a white solid.

Reference： [1]Fan, Yan; Fang, Zhen; Guo, Nihong; Guo, Yinping; Li, Linli; Liu, Yang; Mu, Bo; Xia, Anjie; Xiang, Rong; Xiong, Liang; Yang, Shengyong; Yao, Rui; Zhang, Hailin; Zhang, Rong [European Journal of Medicinal Chemistry, 2022, vol. 238]
[2]Fan, Yan; Fang, Zhen; Guo, Nihong; Guo, Yinping; Li, Linli; Liu, Yang; Mu, Bo; Xia, Anjie; Xiang, Rong; Xiong, Liang; Yang, Shengyong; Yao, Rui; Zhang, Hailin; Zhang, Rong [European Journal of Medicinal Chemistry, 2022, vol. 238]

67
[ 328-42-7 ]
[ 64-17-5 ]
[ 637-04-7 ]
[ 64919-95-5 ]

Yield	Reaction Conditions	Operation in experiment
84.1%	at 85℃; for 12h;	4.1.1. 5-methyl-1-(4-((N-methylsulfiiamoyl)methyl)phenyl)-1H-pyrazole-3-carboxylic acid (12a) General procedure: Step 2. To a solution of 8a (118 mg, 1 mmol) and 4-hydrazino-N-methylbenzenemethanesulfonamide hydrochloride (9, 252 mg, 1 mmol) in anhydrous ethanol (10 mL) was stirred at 85 °C overnight. The reaction was allowed to cool to room temperature and concentrated. The crude material was purified by Isolera Biotage LPLC (PE/EA = 30%) to give a mixture of methyl 5-methyl-1-(4-((N-methylsulflamoyl)methyl)phenyl)-1H-pyrazole-3-carboxylate (10a) and ethyl 5-methyl-1-(4-((N-methylsulflamoyl)methyl)phenyl)-1H-pyrazole-3-carboxylate (11a) as a white solid.
84.1%	at 85℃; for 12h;	4.1.1. 5-methyl-1-(4-((N-methylsulfiiamoyl)methyl)phenyl)-1H-pyrazole-3-carboxylic acid (12a) General procedure: Step 2. To a solution of 8a (118 mg, 1 mmol) and 4-hydrazino-N-methylbenzenemethanesulfonamide hydrochloride (9, 252 mg, 1 mmol) in anhydrous ethanol (10 mL) was stirred at 85 °C overnight. The reaction was allowed to cool to room temperature and concentrated. The crude material was purified by Isolera Biotage LPLC (PE/EA = 30%) to give a mixture of methyl 5-methyl-1-(4-((N-methylsulflamoyl)methyl)phenyl)-1H-pyrazole-3-carboxylate (10a) and ethyl 5-methyl-1-(4-((N-methylsulflamoyl)methyl)phenyl)-1H-pyrazole-3-carboxylate (11a) as a white solid.

Reference： [1]Fan, Yan; Fang, Zhen; Guo, Nihong; Guo, Yinping; Li, Linli; Liu, Yang; Mu, Bo; Xia, Anjie; Xiang, Rong; Xiong, Liang; Yang, Shengyong; Yao, Rui; Zhang, Hailin; Zhang, Rong [European Journal of Medicinal Chemistry, 2022, vol. 238]
[2]Fan, Yan; Fang, Zhen; Guo, Nihong; Guo, Yinping; Li, Linli; Liu, Yang; Mu, Bo; Xia, Anjie; Xiang, Rong; Xiong, Liang; Yang, Shengyong; Yao, Rui; Zhang, Hailin; Zhang, Rong [European Journal of Medicinal Chemistry, 2022, vol. 238]

68
[ 328-42-7 ]
[ 64-17-5 ]
[ 39232-91-2 ]
[ 1164335-98-1 ]

Yield	Reaction Conditions	Operation in experiment
67.2%	at 85℃; for 12h;	4.1.1. 5-methyl-1-(4-((N-methylsulfiiamoyl)methyl)phenyl)-1H-pyrazole-3-carboxylic acid (12a) General procedure: Step 2. To a solution of 8a (118 mg, 1 mmol) and 4-hydrazino-N-methylbenzenemethanesulfonamide hydrochloride (9, 252 mg, 1 mmol) in anhydrous ethanol (10 mL) was stirred at 85 °C overnight. The reaction was allowed to cool to room temperature and concentrated. The crude material was purified by Isolera Biotage LPLC (PE/EA = 30%) to give a mixture of methyl 5-methyl-1-(4-((N-methylsulflamoyl)methyl)phenyl)-1H-pyrazole-3-carboxylate (10a) and ethyl 5-methyl-1-(4-((N-methylsulflamoyl)methyl)phenyl)-1H-pyrazole-3-carboxylate (11a) as a white solid.
67.2%	at 85℃; for 12h;	4.1.1. 5-methyl-1-(4-((N-methylsulfiiamoyl)methyl)phenyl)-1H-pyrazole-3-carboxylic acid (12a) General procedure: Step 2. To a solution of 8a (118 mg, 1 mmol) and 4-hydrazino-N-methylbenzenemethanesulfonamide hydrochloride (9, 252 mg, 1 mmol) in anhydrous ethanol (10 mL) was stirred at 85 °C overnight. The reaction was allowed to cool to room temperature and concentrated. The crude material was purified by Isolera Biotage LPLC (PE/EA = 30%) to give a mixture of methyl 5-methyl-1-(4-((N-methylsulflamoyl)methyl)phenyl)-1H-pyrazole-3-carboxylate (10a) and ethyl 5-methyl-1-(4-((N-methylsulflamoyl)methyl)phenyl)-1H-pyrazole-3-carboxylate (11a) as a white solid.

Reference： [1]Fan, Yan; Fang, Zhen; Guo, Nihong; Guo, Yinping; Li, Linli; Liu, Yang; Mu, Bo; Xia, Anjie; Xiang, Rong; Xiong, Liang; Yang, Shengyong; Yao, Rui; Zhang, Hailin; Zhang, Rong [European Journal of Medicinal Chemistry, 2022, vol. 238]
[2]Fan, Yan; Fang, Zhen; Guo, Nihong; Guo, Yinping; Li, Linli; Liu, Yang; Mu, Bo; Xia, Anjie; Xiang, Rong; Xiong, Liang; Yang, Shengyong; Yao, Rui; Zhang, Hailin; Zhang, Rong [European Journal of Medicinal Chemistry, 2022, vol. 238]

69
[ 328-42-7 ]
[ 64-17-5 ]
[ 41052-75-9 ]
[ 784181-14-2 ]

Yield	Reaction Conditions	Operation in experiment
72.3%	at 85℃; for 12h;	4.1.1. 5-methyl-1-(4-((N-methylsulfiiamoyl)methyl)phenyl)-1H-pyrazole-3-carboxylic acid (12a) General procedure: Step 2. To a solution of 8a (118 mg, 1 mmol) and 4-hydrazino-N-methylbenzenemethanesulfonamide hydrochloride (9, 252 mg, 1 mmol) in anhydrous ethanol (10 mL) was stirred at 85 °C overnight. The reaction was allowed to cool to room temperature and concentrated. The crude material was purified by Isolera Biotage LPLC (PE/EA = 30%) to give a mixture of methyl 5-methyl-1-(4-((N-methylsulflamoyl)methyl)phenyl)-1H-pyrazole-3-carboxylate (10a) and ethyl 5-methyl-1-(4-((N-methylsulflamoyl)methyl)phenyl)-1H-pyrazole-3-carboxylate (11a) as a white solid.
72.3%	at 85℃; for 12h;	4.1.1. 5-methyl-1-(4-((N-methylsulfiiamoyl)methyl)phenyl)-1H-pyrazole-3-carboxylic acid (12a) General procedure: Step 2. To a solution of 8a (118 mg, 1 mmol) and 4-hydrazino-N-methylbenzenemethanesulfonamide hydrochloride (9, 252 mg, 1 mmol) in anhydrous ethanol (10 mL) was stirred at 85 °C overnight. The reaction was allowed to cool to room temperature and concentrated. The crude material was purified by Isolera Biotage LPLC (PE/EA = 30%) to give a mixture of methyl 5-methyl-1-(4-((N-methylsulflamoyl)methyl)phenyl)-1H-pyrazole-3-carboxylate (10a) and ethyl 5-methyl-1-(4-((N-methylsulflamoyl)methyl)phenyl)-1H-pyrazole-3-carboxylate (11a) as a white solid.

Reference： [1]Fan, Yan; Fang, Zhen; Guo, Nihong; Guo, Yinping; Li, Linli; Liu, Yang; Mu, Bo; Xia, Anjie; Xiang, Rong; Xiong, Liang; Yang, Shengyong; Yao, Rui; Zhang, Hailin; Zhang, Rong [European Journal of Medicinal Chemistry, 2022, vol. 238]
[2]Fan, Yan; Fang, Zhen; Guo, Nihong; Guo, Yinping; Li, Linli; Liu, Yang; Mu, Bo; Xia, Anjie; Xiang, Rong; Xiong, Liang; Yang, Shengyong; Yao, Rui; Zhang, Hailin; Zhang, Rong [European Journal of Medicinal Chemistry, 2022, vol. 238]

70
[ 328-42-7 ]
[ 64-17-5 ]
3,4-dimethylphenylhydrazine hydrochloride [ No CAS ]
ethyl 1-(3,4-dimethylphenyl)-5-hydroxy-1H-pyrazole-3-carboxylate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
62.2%	at 85℃; for 12h;	4.1.1. 5-methyl-1-(4-((N-methylsulfiiamoyl)methyl)phenyl)-1H-pyrazole-3-carboxylic acid (12a) General procedure: Step 2. To a solution of 8a (118 mg, 1 mmol) and 4-hydrazino-N-methylbenzenemethanesulfonamide hydrochloride (9, 252 mg, 1 mmol) in anhydrous ethanol (10 mL) was stirred at 85 °C overnight. The reaction was allowed to cool to room temperature and concentrated. The crude material was purified by Isolera Biotage LPLC (PE/EA = 30%) to give a mixture of methyl 5-methyl-1-(4-((N-methylsulflamoyl)methyl)phenyl)-1H-pyrazole-3-carboxylate (10a) and ethyl 5-methyl-1-(4-((N-methylsulflamoyl)methyl)phenyl)-1H-pyrazole-3-carboxylate (11a) as a white solid.
62.2%	at 85℃; for 12h;	4.1.1. 5-methyl-1-(4-((N-methylsulfiiamoyl)methyl)phenyl)-1H-pyrazole-3-carboxylic acid (12a) General procedure: Step 2. To a solution of 8a (118 mg, 1 mmol) and 4-hydrazino-N-methylbenzenemethanesulfonamide hydrochloride (9, 252 mg, 1 mmol) in anhydrous ethanol (10 mL) was stirred at 85 °C overnight. The reaction was allowed to cool to room temperature and concentrated. The crude material was purified by Isolera Biotage LPLC (PE/EA = 30%) to give a mixture of methyl 5-methyl-1-(4-((N-methylsulflamoyl)methyl)phenyl)-1H-pyrazole-3-carboxylate (10a) and ethyl 5-methyl-1-(4-((N-methylsulflamoyl)methyl)phenyl)-1H-pyrazole-3-carboxylate (11a) as a white solid.

Reference： [1]Fan, Yan; Fang, Zhen; Guo, Nihong; Guo, Yinping; Li, Linli; Liu, Yang; Mu, Bo; Xia, Anjie; Xiang, Rong; Xiong, Liang; Yang, Shengyong; Yao, Rui; Zhang, Hailin; Zhang, Rong [European Journal of Medicinal Chemistry, 2022, vol. 238]
[2]Fan, Yan; Fang, Zhen; Guo, Nihong; Guo, Yinping; Li, Linli; Liu, Yang; Mu, Bo; Xia, Anjie; Xiang, Rong; Xiong, Liang; Yang, Shengyong; Yao, Rui; Zhang, Hailin; Zhang, Rong [European Journal of Medicinal Chemistry, 2022, vol. 238]

71
[ 328-42-7 ]
[ 64-17-5 ]
(4-bromo-3-(trifluoromethyl)phenyl)hydrazine hydrochloride [ No CAS ]
ethyl 1-(4-bromo-3-(trifluoromethyl)phenyl)-5-hydroxy-1H-pyrazole-3-carboxylate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
57.3%	at 85℃; for 12h;	4.1.1. 5-methyl-1-(4-((N-methylsulfiiamoyl)methyl)phenyl)-1H-pyrazole-3-carboxylic acid (12a) General procedure: Step 2. To a solution of 8a (118 mg, 1 mmol) and 4-hydrazino-N-methylbenzenemethanesulfonamide hydrochloride (9, 252 mg, 1 mmol) in anhydrous ethanol (10 mL) was stirred at 85 °C overnight. The reaction was allowed to cool to room temperature and concentrated. The crude material was purified by Isolera Biotage LPLC (PE/EA = 30%) to give a mixture of methyl 5-methyl-1-(4-((N-methylsulflamoyl)methyl)phenyl)-1H-pyrazole-3-carboxylate (10a) and ethyl 5-methyl-1-(4-((N-methylsulflamoyl)methyl)phenyl)-1H-pyrazole-3-carboxylate (11a) as a white solid.
57.3%	at 85℃; for 12h;	4.1.1. 5-methyl-1-(4-((N-methylsulfiiamoyl)methyl)phenyl)-1H-pyrazole-3-carboxylic acid (12a) General procedure: Step 2. To a solution of 8a (118 mg, 1 mmol) and 4-hydrazino-N-methylbenzenemethanesulfonamide hydrochloride (9, 252 mg, 1 mmol) in anhydrous ethanol (10 mL) was stirred at 85 °C overnight. The reaction was allowed to cool to room temperature and concentrated. The crude material was purified by Isolera Biotage LPLC (PE/EA = 30%) to give a mixture of methyl 5-methyl-1-(4-((N-methylsulflamoyl)methyl)phenyl)-1H-pyrazole-3-carboxylate (10a) and ethyl 5-methyl-1-(4-((N-methylsulflamoyl)methyl)phenyl)-1H-pyrazole-3-carboxylate (11a) as a white solid.

Reference： [1]Fan, Yan; Fang, Zhen; Guo, Nihong; Guo, Yinping; Li, Linli; Liu, Yang; Mu, Bo; Xia, Anjie; Xiang, Rong; Xiong, Liang; Yang, Shengyong; Yao, Rui; Zhang, Hailin; Zhang, Rong [European Journal of Medicinal Chemistry, 2022, vol. 238]
[2]Fan, Yan; Fang, Zhen; Guo, Nihong; Guo, Yinping; Li, Linli; Liu, Yang; Mu, Bo; Xia, Anjie; Xiang, Rong; Xiong, Liang; Yang, Shengyong; Yao, Rui; Zhang, Hailin; Zhang, Rong [European Journal of Medicinal Chemistry, 2022, vol. 238]

72
[ 328-42-7 ]
[ 64-17-5 ]
(3-bromo-4-methylphenyl)hydrazine hydrochloride [ No CAS ]
ethyl 1-(3-bromo-4-methylphenyl)-5-hydroxy-1H-pyrazole-3-carboxylate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
60.6%	at 85℃; for 12h;	4.1.1. 5-methyl-1-(4-((N-methylsulfiiamoyl)methyl)phenyl)-1H-pyrazole-3-carboxylic acid (12a) General procedure: Step 2. To a solution of 8a (118 mg, 1 mmol) and 4-hydrazino-N-methylbenzenemethanesulfonamide hydrochloride (9, 252 mg, 1 mmol) in anhydrous ethanol (10 mL) was stirred at 85 °C overnight. The reaction was allowed to cool to room temperature and concentrated. The crude material was purified by Isolera Biotage LPLC (PE/EA = 30%) to give a mixture of methyl 5-methyl-1-(4-((N-methylsulflamoyl)methyl)phenyl)-1H-pyrazole-3-carboxylate (10a) and ethyl 5-methyl-1-(4-((N-methylsulflamoyl)methyl)phenyl)-1H-pyrazole-3-carboxylate (11a) as a white solid.
60.6%	at 85℃; for 12h;	4.1.1. 5-methyl-1-(4-((N-methylsulfiiamoyl)methyl)phenyl)-1H-pyrazole-3-carboxylic acid (12a) General procedure: Step 2. To a solution of 8a (118 mg, 1 mmol) and 4-hydrazino-N-methylbenzenemethanesulfonamide hydrochloride (9, 252 mg, 1 mmol) in anhydrous ethanol (10 mL) was stirred at 85 °C overnight. The reaction was allowed to cool to room temperature and concentrated. The crude material was purified by Isolera Biotage LPLC (PE/EA = 30%) to give a mixture of methyl 5-methyl-1-(4-((N-methylsulflamoyl)methyl)phenyl)-1H-pyrazole-3-carboxylate (10a) and ethyl 5-methyl-1-(4-((N-methylsulflamoyl)methyl)phenyl)-1H-pyrazole-3-carboxylate (11a) as a white solid.

Reference： [1]Fan, Yan; Fang, Zhen; Guo, Nihong; Guo, Yinping; Li, Linli; Liu, Yang; Mu, Bo; Xia, Anjie; Xiang, Rong; Xiong, Liang; Yang, Shengyong; Yao, Rui; Zhang, Hailin; Zhang, Rong [European Journal of Medicinal Chemistry, 2022, vol. 238]
[2]Fan, Yan; Fang, Zhen; Guo, Nihong; Guo, Yinping; Li, Linli; Liu, Yang; Mu, Bo; Xia, Anjie; Xiang, Rong; Xiong, Liang; Yang, Shengyong; Yao, Rui; Zhang, Hailin; Zhang, Rong [European Journal of Medicinal Chemistry, 2022, vol. 238]

73
[ 328-42-7 ]
[ 64-17-5 ]
(4-methyl-3-(trifluoromethyl)phenyl)hydrazine hydrochloride [ No CAS ]
ethyl 5-hydroxy-1-(4-methyl-3-(trifluoromethyl)phenyl)-1H-pyrazole-3-carboxylate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
60.2%	at 85℃; for 12h;	4.1.1. 5-methyl-1-(4-((N-methylsulfiiamoyl)methyl)phenyl)-1H-pyrazole-3-carboxylic acid (12a) General procedure: Step 2. To a solution of 8a (118 mg, 1 mmol) and 4-hydrazino-N-methylbenzenemethanesulfonamide hydrochloride (9, 252 mg, 1 mmol) in anhydrous ethanol (10 mL) was stirred at 85 °C overnight. The reaction was allowed to cool to room temperature and concentrated. The crude material was purified by Isolera Biotage LPLC (PE/EA = 30%) to give a mixture of methyl 5-methyl-1-(4-((N-methylsulflamoyl)methyl)phenyl)-1H-pyrazole-3-carboxylate (10a) and ethyl 5-methyl-1-(4-((N-methylsulflamoyl)methyl)phenyl)-1H-pyrazole-3-carboxylate (11a) as a white solid.
60.2%	at 85℃; for 12h;	4.1.1. 5-methyl-1-(4-((N-methylsulfiiamoyl)methyl)phenyl)-1H-pyrazole-3-carboxylic acid (12a) General procedure: Step 2. To a solution of 8a (118 mg, 1 mmol) and 4-hydrazino-N-methylbenzenemethanesulfonamide hydrochloride (9, 252 mg, 1 mmol) in anhydrous ethanol (10 mL) was stirred at 85 °C overnight. The reaction was allowed to cool to room temperature and concentrated. The crude material was purified by Isolera Biotage LPLC (PE/EA = 30%) to give a mixture of methyl 5-methyl-1-(4-((N-methylsulflamoyl)methyl)phenyl)-1H-pyrazole-3-carboxylate (10a) and ethyl 5-methyl-1-(4-((N-methylsulflamoyl)methyl)phenyl)-1H-pyrazole-3-carboxylate (11a) as a white solid.

Reference： [1]Fan, Yan; Fang, Zhen; Guo, Nihong; Guo, Yinping; Li, Linli; Liu, Yang; Mu, Bo; Xia, Anjie; Xiang, Rong; Xiong, Liang; Yang, Shengyong; Yao, Rui; Zhang, Hailin; Zhang, Rong [European Journal of Medicinal Chemistry, 2022, vol. 238]
[2]Fan, Yan; Fang, Zhen; Guo, Nihong; Guo, Yinping; Li, Linli; Liu, Yang; Mu, Bo; Xia, Anjie; Xiang, Rong; Xiong, Liang; Yang, Shengyong; Yao, Rui; Zhang, Hailin; Zhang, Rong [European Journal of Medicinal Chemistry, 2022, vol. 238]

74
[ 328-42-7 ]
[ 64-17-5 ]
[ 502496-25-5 ]
[ 1138036-84-6 ]

Yield	Reaction Conditions	Operation in experiment
73.3%	at 85℃; for 12h;	4.1.1. 5-methyl-1-(4-((N-methylsulfiiamoyl)methyl)phenyl)-1H-pyrazole-3-carboxylic acid (12a) General procedure: Step 2. To a solution of 8a (118 mg, 1 mmol) and 4-hydrazino-N-methylbenzenemethanesulfonamide hydrochloride (9, 252 mg, 1 mmol) in anhydrous ethanol (10 mL) was stirred at 85 °C overnight. The reaction was allowed to cool to room temperature and concentrated. The crude material was purified by Isolera Biotage LPLC (PE/EA = 30%) to give a mixture of methyl 5-methyl-1-(4-((N-methylsulflamoyl)methyl)phenyl)-1H-pyrazole-3-carboxylate (10a) and ethyl 5-methyl-1-(4-((N-methylsulflamoyl)methyl)phenyl)-1H-pyrazole-3-carboxylate (11a) as a white solid.
73.3%	at 85℃; for 12h;	4.1.1. 5-methyl-1-(4-((N-methylsulfiiamoyl)methyl)phenyl)-1H-pyrazole-3-carboxylic acid (12a) General procedure: Step 2. To a solution of 8a (118 mg, 1 mmol) and 4-hydrazino-N-methylbenzenemethanesulfonamide hydrochloride (9, 252 mg, 1 mmol) in anhydrous ethanol (10 mL) was stirred at 85 °C overnight. The reaction was allowed to cool to room temperature and concentrated. The crude material was purified by Isolera Biotage LPLC (PE/EA = 30%) to give a mixture of methyl 5-methyl-1-(4-((N-methylsulflamoyl)methyl)phenyl)-1H-pyrazole-3-carboxylate (10a) and ethyl 5-methyl-1-(4-((N-methylsulflamoyl)methyl)phenyl)-1H-pyrazole-3-carboxylate (11a) as a white solid.

Reference： [1]Fan, Yan; Fang, Zhen; Guo, Nihong; Guo, Yinping; Li, Linli; Liu, Yang; Mu, Bo; Xia, Anjie; Xiang, Rong; Xiong, Liang; Yang, Shengyong; Yao, Rui; Zhang, Hailin; Zhang, Rong [European Journal of Medicinal Chemistry, 2022, vol. 238]
[2]Fan, Yan; Fang, Zhen; Guo, Nihong; Guo, Yinping; Li, Linli; Liu, Yang; Mu, Bo; Xia, Anjie; Xiang, Rong; Xiong, Liang; Yang, Shengyong; Yao, Rui; Zhang, Hailin; Zhang, Rong [European Journal of Medicinal Chemistry, 2022, vol. 238]

75
[ 328-42-7 ]
[ 64-17-5 ]
N-(4-hydrazinylphenyl)methanesulfonamide hydrochloride [ No CAS ]
ethyl 5-hydroxy-1-(4-(methylsulfonamido)phenyl)-1H-pyrazole-3-carboxylate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
84.3%	at 85℃; for 12h;	4.1.1. 5-methyl-1-(4-((N-methylsulfiiamoyl)methyl)phenyl)-1H-pyrazole-3-carboxylic acid (12a) General procedure: Step 2. To a solution of 8a (118 mg, 1 mmol) and 4-hydrazino-N-methylbenzenemethanesulfonamide hydrochloride (9, 252 mg, 1 mmol) in anhydrous ethanol (10 mL) was stirred at 85 °C overnight. The reaction was allowed to cool to room temperature and concentrated. The crude material was purified by Isolera Biotage LPLC (PE/EA = 30%) to give a mixture of methyl 5-methyl-1-(4-((N-methylsulflamoyl)methyl)phenyl)-1H-pyrazole-3-carboxylate (10a) and ethyl 5-methyl-1-(4-((N-methylsulflamoyl)methyl)phenyl)-1H-pyrazole-3-carboxylate (11a) as a white solid.
84.3%	at 85℃; for 12h;	4.1.1. 5-methyl-1-(4-((N-methylsulfiiamoyl)methyl)phenyl)-1H-pyrazole-3-carboxylic acid (12a) General procedure: Step 2. To a solution of 8a (118 mg, 1 mmol) and 4-hydrazino-N-methylbenzenemethanesulfonamide hydrochloride (9, 252 mg, 1 mmol) in anhydrous ethanol (10 mL) was stirred at 85 °C overnight. The reaction was allowed to cool to room temperature and concentrated. The crude material was purified by Isolera Biotage LPLC (PE/EA = 30%) to give a mixture of methyl 5-methyl-1-(4-((N-methylsulflamoyl)methyl)phenyl)-1H-pyrazole-3-carboxylate (10a) and ethyl 5-methyl-1-(4-((N-methylsulflamoyl)methyl)phenyl)-1H-pyrazole-3-carboxylate (11a) as a white solid.

Reference： [1]Fan, Yan; Fang, Zhen; Guo, Nihong; Guo, Yinping; Li, Linli; Liu, Yang; Mu, Bo; Xia, Anjie; Xiang, Rong; Xiong, Liang; Yang, Shengyong; Yao, Rui; Zhang, Hailin; Zhang, Rong [European Journal of Medicinal Chemistry, 2022, vol. 238]
[2]Fan, Yan; Fang, Zhen; Guo, Nihong; Guo, Yinping; Li, Linli; Liu, Yang; Mu, Bo; Xia, Anjie; Xiang, Rong; Xiong, Liang; Yang, Shengyong; Yao, Rui; Zhang, Hailin; Zhang, Rong [European Journal of Medicinal Chemistry, 2022, vol. 238]

76
[ 328-42-7 ]
[ 64-17-5 ]
[ 334981-11-2 ]
ethyl 5-hydroxy-1-(4-((pyrrolidin-1-ylsulfonyl)methyl)phenyl)-1H-pyrazole-3-carboxylate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
70.2%	at 85℃; for 12h;	4.1.1. 5-methyl-1-(4-((N-methylsulfiiamoyl)methyl)phenyl)-1H-pyrazole-3-carboxylic acid (12a) General procedure: Step 2. To a solution of 8a (118 mg, 1 mmol) and 4-hydrazino-N-methylbenzenemethanesulfonamide hydrochloride (9, 252 mg, 1 mmol) in anhydrous ethanol (10 mL) was stirred at 85 °C overnight. The reaction was allowed to cool to room temperature and concentrated. The crude material was purified by Isolera Biotage LPLC (PE/EA = 30%) to give a mixture of methyl 5-methyl-1-(4-((N-methylsulflamoyl)methyl)phenyl)-1H-pyrazole-3-carboxylate (10a) and ethyl 5-methyl-1-(4-((N-methylsulflamoyl)methyl)phenyl)-1H-pyrazole-3-carboxylate (11a) as a white solid.
70.2%	at 85℃; for 12h;	4.1.1. 5-methyl-1-(4-((N-methylsulfiiamoyl)methyl)phenyl)-1H-pyrazole-3-carboxylic acid (12a) General procedure: Step 2. To a solution of 8a (118 mg, 1 mmol) and 4-hydrazino-N-methylbenzenemethanesulfonamide hydrochloride (9, 252 mg, 1 mmol) in anhydrous ethanol (10 mL) was stirred at 85 °C overnight. The reaction was allowed to cool to room temperature and concentrated. The crude material was purified by Isolera Biotage LPLC (PE/EA = 30%) to give a mixture of methyl 5-methyl-1-(4-((N-methylsulflamoyl)methyl)phenyl)-1H-pyrazole-3-carboxylate (10a) and ethyl 5-methyl-1-(4-((N-methylsulflamoyl)methyl)phenyl)-1H-pyrazole-3-carboxylate (11a) as a white solid.

Reference： [1]Fan, Yan; Fang, Zhen; Guo, Nihong; Guo, Yinping; Li, Linli; Liu, Yang; Mu, Bo; Xia, Anjie; Xiang, Rong; Xiong, Liang; Yang, Shengyong; Yao, Rui; Zhang, Hailin; Zhang, Rong [European Journal of Medicinal Chemistry, 2022, vol. 238]
[2]Fan, Yan; Fang, Zhen; Guo, Nihong; Guo, Yinping; Li, Linli; Liu, Yang; Mu, Bo; Xia, Anjie; Xiang, Rong; Xiong, Liang; Yang, Shengyong; Yao, Rui; Zhang, Hailin; Zhang, Rong [European Journal of Medicinal Chemistry, 2022, vol. 238]

77
[ 328-42-7 ]
[ 64-17-5 ]
N-(4-fluorobenzyl)-1-(4-hydrazinylphenyl)methanesulfonamide hydrochloride [ No CAS ]
ethyl 1-(4-((N-(4-fluorobenzyl)sulfamoyl)methyl)phenyl)-5-hydroxy-1H-pyrazole-3-carboxylate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
67.3%	at 85℃; for 12h;	4.1.1. 5-methyl-1-(4-((N-methylsulfiiamoyl)methyl)phenyl)-1H-pyrazole-3-carboxylic acid (12a) General procedure: Step 2. To a solution of 8a (118 mg, 1 mmol) and 4-hydrazino-N-methylbenzenemethanesulfonamide hydrochloride (9, 252 mg, 1 mmol) in anhydrous ethanol (10 mL) was stirred at 85 °C overnight. The reaction was allowed to cool to room temperature and concentrated. The crude material was purified by Isolera Biotage LPLC (PE/EA = 30%) to give a mixture of methyl 5-methyl-1-(4-((N-methylsulflamoyl)methyl)phenyl)-1H-pyrazole-3-carboxylate (10a) and ethyl 5-methyl-1-(4-((N-methylsulflamoyl)methyl)phenyl)-1H-pyrazole-3-carboxylate (11a) as a white solid.
67.3%	at 85℃; for 12h;	4.1.1. 5-methyl-1-(4-((N-methylsulfiiamoyl)methyl)phenyl)-1H-pyrazole-3-carboxylic acid (12a) General procedure: Step 2. To a solution of 8a (118 mg, 1 mmol) and 4-hydrazino-N-methylbenzenemethanesulfonamide hydrochloride (9, 252 mg, 1 mmol) in anhydrous ethanol (10 mL) was stirred at 85 °C overnight. The reaction was allowed to cool to room temperature and concentrated. The crude material was purified by Isolera Biotage LPLC (PE/EA = 30%) to give a mixture of methyl 5-methyl-1-(4-((N-methylsulflamoyl)methyl)phenyl)-1H-pyrazole-3-carboxylate (10a) and ethyl 5-methyl-1-(4-((N-methylsulflamoyl)methyl)phenyl)-1H-pyrazole-3-carboxylate (11a) as a white solid.

Reference： [1]Fan, Yan; Fang, Zhen; Guo, Nihong; Guo, Yinping; Li, Linli; Liu, Yang; Mu, Bo; Xia, Anjie; Xiang, Rong; Xiong, Liang; Yang, Shengyong; Yao, Rui; Zhang, Hailin; Zhang, Rong [European Journal of Medicinal Chemistry, 2022, vol. 238]
[2]Fan, Yan; Fang, Zhen; Guo, Nihong; Guo, Yinping; Li, Linli; Liu, Yang; Mu, Bo; Xia, Anjie; Xiang, Rong; Xiong, Liang; Yang, Shengyong; Yao, Rui; Zhang, Hailin; Zhang, Rong [European Journal of Medicinal Chemistry, 2022, vol. 238]

78
[ 328-42-7 ]
[ 64-17-5 ]
N-(3-fluorobenzyl)-1-(4-hydrazinylphenyl)methanesulfonamide hydrochloride [ No CAS ]
ethyl 1-(4-((N-(3-fluorobenzyl)sulfamoyl)methyl)phenyl)-5-hydroxy-1H-pyrazole-3-carboxylate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
74.3%	at 85℃; for 12h;	4.1.1. 5-methyl-1-(4-((N-methylsulfiiamoyl)methyl)phenyl)-1H-pyrazole-3-carboxylic acid (12a) General procedure: Step 2. To a solution of 8a (118 mg, 1 mmol) and 4-hydrazino-N-methylbenzenemethanesulfonamide hydrochloride (9, 252 mg, 1 mmol) in anhydrous ethanol (10 mL) was stirred at 85 °C overnight. The reaction was allowed to cool to room temperature and concentrated. The crude material was purified by Isolera Biotage LPLC (PE/EA = 30%) to give a mixture of methyl 5-methyl-1-(4-((N-methylsulflamoyl)methyl)phenyl)-1H-pyrazole-3-carboxylate (10a) and ethyl 5-methyl-1-(4-((N-methylsulflamoyl)methyl)phenyl)-1H-pyrazole-3-carboxylate (11a) as a white solid.
74.3%	at 85℃; for 12h;	4.1.1. 5-methyl-1-(4-((N-methylsulfiiamoyl)methyl)phenyl)-1H-pyrazole-3-carboxylic acid (12a) General procedure: Step 2. To a solution of 8a (118 mg, 1 mmol) and 4-hydrazino-N-methylbenzenemethanesulfonamide hydrochloride (9, 252 mg, 1 mmol) in anhydrous ethanol (10 mL) was stirred at 85 °C overnight. The reaction was allowed to cool to room temperature and concentrated. The crude material was purified by Isolera Biotage LPLC (PE/EA = 30%) to give a mixture of methyl 5-methyl-1-(4-((N-methylsulflamoyl)methyl)phenyl)-1H-pyrazole-3-carboxylate (10a) and ethyl 5-methyl-1-(4-((N-methylsulflamoyl)methyl)phenyl)-1H-pyrazole-3-carboxylate (11a) as a white solid.

Reference： [1]Fan, Yan; Fang, Zhen; Guo, Nihong; Guo, Yinping; Li, Linli; Liu, Yang; Mu, Bo; Xia, Anjie; Xiang, Rong; Xiong, Liang; Yang, Shengyong; Yao, Rui; Zhang, Hailin; Zhang, Rong [European Journal of Medicinal Chemistry, 2022, vol. 238]
[2]Fan, Yan; Fang, Zhen; Guo, Nihong; Guo, Yinping; Li, Linli; Liu, Yang; Mu, Bo; Xia, Anjie; Xiang, Rong; Xiong, Liang; Yang, Shengyong; Yao, Rui; Zhang, Hailin; Zhang, Rong [European Journal of Medicinal Chemistry, 2022, vol. 238]

79
[ 328-42-7 ]
[ 64-17-5 ]
N-(2-fluorobenzyl)-1-(4-hydrazinylphenyl)methanesulfonamide hydrochloride [ No CAS ]
ethyl 1-(4-((N-(2-fluorobenzyl)sulfamoyl)methyl)phenyl)-5-hydroxy-1H-pyrazole-3-carboxylate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
71.5%	at 85℃; for 12h;	4.1.1. 5-methyl-1-(4-((N-methylsulfiiamoyl)methyl)phenyl)-1H-pyrazole-3-carboxylic acid (12a) General procedure: Step 2. To a solution of 8a (118 mg, 1 mmol) and 4-hydrazino-N-methylbenzenemethanesulfonamide hydrochloride (9, 252 mg, 1 mmol) in anhydrous ethanol (10 mL) was stirred at 85 °C overnight. The reaction was allowed to cool to room temperature and concentrated. The crude material was purified by Isolera Biotage LPLC (PE/EA = 30%) to give a mixture of methyl 5-methyl-1-(4-((N-methylsulflamoyl)methyl)phenyl)-1H-pyrazole-3-carboxylate (10a) and ethyl 5-methyl-1-(4-((N-methylsulflamoyl)methyl)phenyl)-1H-pyrazole-3-carboxylate (11a) as a white solid.
71.5%	at 85℃; for 12h;	4.1.1. 5-methyl-1-(4-((N-methylsulfiiamoyl)methyl)phenyl)-1H-pyrazole-3-carboxylic acid (12a) General procedure: Step 2. To a solution of 8a (118 mg, 1 mmol) and 4-hydrazino-N-methylbenzenemethanesulfonamide hydrochloride (9, 252 mg, 1 mmol) in anhydrous ethanol (10 mL) was stirred at 85 °C overnight. The reaction was allowed to cool to room temperature and concentrated. The crude material was purified by Isolera Biotage LPLC (PE/EA = 30%) to give a mixture of methyl 5-methyl-1-(4-((N-methylsulflamoyl)methyl)phenyl)-1H-pyrazole-3-carboxylate (10a) and ethyl 5-methyl-1-(4-((N-methylsulflamoyl)methyl)phenyl)-1H-pyrazole-3-carboxylate (11a) as a white solid.

Reference： [1]Fan, Yan; Fang, Zhen; Guo, Nihong; Guo, Yinping; Li, Linli; Liu, Yang; Mu, Bo; Xia, Anjie; Xiang, Rong; Xiong, Liang; Yang, Shengyong; Yao, Rui; Zhang, Hailin; Zhang, Rong [European Journal of Medicinal Chemistry, 2022, vol. 238]
[2]Fan, Yan; Fang, Zhen; Guo, Nihong; Guo, Yinping; Li, Linli; Liu, Yang; Mu, Bo; Xia, Anjie; Xiang, Rong; Xiong, Liang; Yang, Shengyong; Yao, Rui; Zhang, Hailin; Zhang, Rong [European Journal of Medicinal Chemistry, 2022, vol. 238]

80
[ 328-42-7 ]
[ 64-17-5 ]
[ 59-88-1 ]
[ 27241-29-8 ]

Yield	Reaction Conditions	Operation in experiment
72%	at 85℃; for 12h;	4.1.1. 5-methyl-1-(4-((N-methylsulfiiamoyl)methyl)phenyl)-1H-pyrazole-3-carboxylic acid (12a) General procedure: Step 2. To a solution of 8a (118 mg, 1 mmol) and 4-hydrazino-N-methylbenzenemethanesulfonamide hydrochloride (9, 252 mg, 1 mmol)in anhydrous ethanol (10 mL) was stirred at 85 °C overnight. The reaction was allowed to cool to room temperature and concentrated. The crude material was purified by Isolera Biotage LPLC (PE/EA = 30%) to give a mixture of methyl 5-methyl-1-(4-((N-methylsulflamoyl)methyl)phenyl)-1H-pyrazole-3-carboxylate (10a) and ethyl 5-methyl-1-(4-((N-methylsulflamoyl)methyl)phenyl)-1H-pyrazole-3-carboxylate (11a) as awhite solid.
72%	at 85℃; for 12h;	4.1.1. 5-methyl-1-(4-((N-methylsulfiiamoyl)methyl)phenyl)-1H-pyrazole-3-carboxylic acid (12a) General procedure: Step 2. To a solution of 8a (118 mg, 1 mmol) and 4-hydrazino-N-methylbenzenemethanesulfonamide hydrochloride (9, 252 mg, 1 mmol)in anhydrous ethanol (10 mL) was stirred at 85 °C overnight. The reaction was allowed to cool to room temperature and concentrated. The crude material was purified by Isolera Biotage LPLC (PE/EA = 30%) to give a mixture of methyl 5-methyl-1-(4-((N-methylsulflamoyl)methyl)phenyl)-1H-pyrazole-3-carboxylate (10a) and ethyl 5-methyl-1-(4-((N-methylsulflamoyl)methyl)phenyl)-1H-pyrazole-3-carboxylate (11a) as awhite solid.

Reference： [1]Fan, Yan; Fang, Zhen; Guo, Nihong; Guo, Yinping; Li, Linli; Liu, Yang; Mu, Bo; Xia, Anjie; Xiang, Rong; Xiong, Liang; Yang, Shengyong; Yao, Rui; Zhang, Hailin; Zhang, Rong [European Journal of Medicinal Chemistry, 2022, vol. 238]
[2]Fan, Yan; Fang, Zhen; Guo, Nihong; Guo, Yinping; Li, Linli; Liu, Yang; Mu, Bo; Xia, Anjie; Xiang, Rong; Xiong, Liang; Yang, Shengyong; Yao, Rui; Zhang, Hailin; Zhang, Rong [European Journal of Medicinal Chemistry, 2022, vol. 238]

81
[ 328-42-7 ]
[ 64-17-5 ]
[ 823-85-8 ]
ethyl 1-(4-fluorophenyl)-5-hydroxy-1H-pyrazole-3-carboxylate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
68.4%	at 85℃; for 12h;	4.1.1. 5-methyl-1-(4-((N-methylsulfiiamoyl)methyl)phenyl)-1H-pyrazole-3-carboxylic acid (12a) General procedure: Step 2. To a solution of 8a (118 mg, 1 mmol) and 4-hydrazino-N-methylbenzenemethanesulfonamide hydrochloride (9, 252 mg, 1 mmol) in anhydrous ethanol (10 mL) was stirred at 85 °C overnight. The reaction was allowed to cool to room temperature and concentrated. The crude material was purified by Isolera Biotage LPLC (PE/EA = 30%) to give a mixture of methyl 5-methyl-1-(4-((N-methylsulflamoyl)methyl)phenyl)-1H-pyrazole-3-carboxylate (10a) and ethyl 5-methyl-1-(4-((N-methylsulflamoyl)methyl)phenyl)-1H-pyrazole-3-carboxylate (11a) as a white solid.
68.4%	at 85℃; for 12h;	4.1.1. 5-methyl-1-(4-((N-methylsulfiiamoyl)methyl)phenyl)-1H-pyrazole-3-carboxylic acid (12a) General procedure: Step 2. To a solution of 8a (118 mg, 1 mmol) and 4-hydrazino-N-methylbenzenemethanesulfonamide hydrochloride (9, 252 mg, 1 mmol) in anhydrous ethanol (10 mL) was stirred at 85 °C overnight. The reaction was allowed to cool to room temperature and concentrated. The crude material was purified by Isolera Biotage LPLC (PE/EA = 30%) to give a mixture of methyl 5-methyl-1-(4-((N-methylsulflamoyl)methyl)phenyl)-1H-pyrazole-3-carboxylate (10a) and ethyl 5-methyl-1-(4-((N-methylsulflamoyl)methyl)phenyl)-1H-pyrazole-3-carboxylate (11a) as a white solid.

Reference： [1]Fan, Yan; Fang, Zhen; Guo, Nihong; Guo, Yinping; Li, Linli; Liu, Yang; Mu, Bo; Xia, Anjie; Xiang, Rong; Xiong, Liang; Yang, Shengyong; Yao, Rui; Zhang, Hailin; Zhang, Rong [European Journal of Medicinal Chemistry, 2022, vol. 238]
[2]Fan, Yan; Fang, Zhen; Guo, Nihong; Guo, Yinping; Li, Linli; Liu, Yang; Mu, Bo; Xia, Anjie; Xiang, Rong; Xiong, Liang; Yang, Shengyong; Yao, Rui; Zhang, Hailin; Zhang, Rong [European Journal of Medicinal Chemistry, 2022, vol. 238]

82
[ 328-42-7 ]
[ 64-17-5 ]
[ 1073-70-7 ]
[ 64919-93-3 ]

Yield	Reaction Conditions	Operation in experiment
78%	at 85℃; for 12h;	4.1.1. 5-methyl-1-(4-((N-methylsulfiiamoyl)methyl)phenyl)-1H-pyrazole-3-carboxylic acid (12a) General procedure: Step 2. To a solution of 8a (118 mg, 1 mmol) and 4-hydrazino-N-methylbenzenemethanesulfonamide hydrochloride (9, 252 mg, 1 mmol) in anhydrous ethanol (10 mL) was stirred at 85 °C overnight. The reaction was allowed to cool to room temperature and concentrated. The crude material was purified by Isolera Biotage LPLC (PE/EA = 30%) to give a mixture of methyl 5-methyl-1-(4-((N-methylsulflamoyl)methyl)phenyl)-1H-pyrazole-3-carboxylate (10a) and ethyl 5-methyl-1-(4-((N-methylsulflamoyl)methyl)phenyl)-1H-pyrazole-3-carboxylate (11a) as a white solid.
78%	at 85℃; for 12h;	4.1.1. 5-methyl-1-(4-((N-methylsulfiiamoyl)methyl)phenyl)-1H-pyrazole-3-carboxylic acid (12a) General procedure: Step 2. To a solution of 8a (118 mg, 1 mmol) and 4-hydrazino-N-methylbenzenemethanesulfonamide hydrochloride (9, 252 mg, 1 mmol) in anhydrous ethanol (10 mL) was stirred at 85 °C overnight. The reaction was allowed to cool to room temperature and concentrated. The crude material was purified by Isolera Biotage LPLC (PE/EA = 30%) to give a mixture of methyl 5-methyl-1-(4-((N-methylsulflamoyl)methyl)phenyl)-1H-pyrazole-3-carboxylate (10a) and ethyl 5-methyl-1-(4-((N-methylsulflamoyl)methyl)phenyl)-1H-pyrazole-3-carboxylate (11a) as a white solid.

Reference： [1]Fan, Yan; Fang, Zhen; Guo, Nihong; Guo, Yinping; Li, Linli; Liu, Yang; Mu, Bo; Xia, Anjie; Xiang, Rong; Xiong, Liang; Yang, Shengyong; Yao, Rui; Zhang, Hailin; Zhang, Rong [European Journal of Medicinal Chemistry, 2022, vol. 238]
[2]Fan, Yan; Fang, Zhen; Guo, Nihong; Guo, Yinping; Li, Linli; Liu, Yang; Mu, Bo; Xia, Anjie; Xiang, Rong; Xiong, Liang; Yang, Shengyong; Yao, Rui; Zhang, Hailin; Zhang, Rong [European Journal of Medicinal Chemistry, 2022, vol. 238]

83
[ 328-42-7 ]
[ 64-17-5 ]
[ 622-88-8 ]
ethyl 1-(4-bromophenyl)-5-hydroxy-1H-pyrazole-3-carboxylate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
76.2%	at 85℃; for 12h;	4.1.1. 5-methyl-1-(4-((N-methylsulfiiamoyl)methyl)phenyl)-1H-pyrazole-3-carboxylic acid (12a) General procedure: Step 2. To a solution of 8a (118 mg, 1 mmol) and 4-hydrazino-N-methylbenzenemethanesulfonamide hydrochloride (9, 252 mg, 1 mmol) in anhydrous ethanol (10 mL) was stirred at 85 °C overnight. The reaction was allowed to cool to room temperature and concentrated. The crude material was purified by Isolera Biotage LPLC (PE/EA = 30%) to give a mixture of methyl 5-methyl-1-(4-((N-methylsulflamoyl)methyl)phenyl)-1H-pyrazole-3-carboxylate (10a) and ethyl 5-methyl-1-(4-((N-methylsulflamoyl)methyl)phenyl)-1H-pyrazole-3-carboxylate (11a) as a white solid.
76.2%	at 85℃; for 12h;	4.1.1. 5-methyl-1-(4-((N-methylsulfiiamoyl)methyl)phenyl)-1H-pyrazole-3-carboxylic acid (12a) General procedure: Step 2. To a solution of 8a (118 mg, 1 mmol) and 4-hydrazino-N-methylbenzenemethanesulfonamide hydrochloride (9, 252 mg, 1 mmol) in anhydrous ethanol (10 mL) was stirred at 85 °C overnight. The reaction was allowed to cool to room temperature and concentrated. The crude material was purified by Isolera Biotage LPLC (PE/EA = 30%) to give a mixture of methyl 5-methyl-1-(4-((N-methylsulflamoyl)methyl)phenyl)-1H-pyrazole-3-carboxylate (10a) and ethyl 5-methyl-1-(4-((N-methylsulflamoyl)methyl)phenyl)-1H-pyrazole-3-carboxylate (11a) as a white solid.

Reference： [1]Fan, Yan; Fang, Zhen; Guo, Nihong; Guo, Yinping; Li, Linli; Liu, Yang; Mu, Bo; Xia, Anjie; Xiang, Rong; Xiong, Liang; Yang, Shengyong; Yao, Rui; Zhang, Hailin; Zhang, Rong [European Journal of Medicinal Chemistry, 2022, vol. 238]
[2]Fan, Yan; Fang, Zhen; Guo, Nihong; Guo, Yinping; Li, Linli; Liu, Yang; Mu, Bo; Xia, Anjie; Xiang, Rong; Xiong, Liang; Yang, Shengyong; Yao, Rui; Zhang, Hailin; Zhang, Rong [European Journal of Medicinal Chemistry, 2022, vol. 238]

84
[ 328-42-7 ]
[ 64-17-5 ]
[ 637-60-5 ]
[ 64919-94-4 ]

Yield	Reaction Conditions	Operation in experiment
77.6%	at 85℃; for 12h;	4.1.1. 5-methyl-1-(4-((N-methylsulfiiamoyl)methyl)phenyl)-1H-pyrazole-3-carboxylic acid (12a) General procedure: Step 2. To a solution of 8a (118 mg, 1 mmol) and 4-hydrazino-N-methylbenzenemethanesulfonamide hydrochloride (9, 252 mg, 1 mmol) in anhydrous ethanol (10 mL) was stirred at 85 °C overnight. The reaction was allowed to cool to room temperature and concentrated. The crude material was purified by Isolera Biotage LPLC (PE/EA = 30%) to give a mixture of methyl 5-methyl-1-(4-((N-methylsulflamoyl)methyl)phenyl)-1H-pyrazole-3-carboxylate (10a) and ethyl 5-methyl-1-(4-((N-methylsulflamoyl)methyl)phenyl)-1H-pyrazole-3-carboxylate (11a) as a white solid.
77.6%	at 85℃; for 12h;	4.1.1. 5-methyl-1-(4-((N-methylsulfiiamoyl)methyl)phenyl)-1H-pyrazole-3-carboxylic acid (12a) General procedure: Step 2. To a solution of 8a (118 mg, 1 mmol) and 4-hydrazino-N-methylbenzenemethanesulfonamide hydrochloride (9, 252 mg, 1 mmol) in anhydrous ethanol (10 mL) was stirred at 85 °C overnight. The reaction was allowed to cool to room temperature and concentrated. The crude material was purified by Isolera Biotage LPLC (PE/EA = 30%) to give a mixture of methyl 5-methyl-1-(4-((N-methylsulflamoyl)methyl)phenyl)-1H-pyrazole-3-carboxylate (10a) and ethyl 5-methyl-1-(4-((N-methylsulflamoyl)methyl)phenyl)-1H-pyrazole-3-carboxylate (11a) as a white solid.

Reference： [1]Fan, Yan; Fang, Zhen; Guo, Nihong; Guo, Yinping; Li, Linli; Liu, Yang; Mu, Bo; Xia, Anjie; Xiang, Rong; Xiong, Liang; Yang, Shengyong; Yao, Rui; Zhang, Hailin; Zhang, Rong [European Journal of Medicinal Chemistry, 2022, vol. 238]
[2]Fan, Yan; Fang, Zhen; Guo, Nihong; Guo, Yinping; Li, Linli; Liu, Yang; Mu, Bo; Xia, Anjie; Xiang, Rong; Xiong, Liang; Yang, Shengyong; Yao, Rui; Zhang, Hailin; Zhang, Rong [European Journal of Medicinal Chemistry, 2022, vol. 238]

85
[ 328-42-7 ]
[ 64-17-5 ]
[ 2863-98-1 ]
ethyl 1-(4-cyanophenyl)-5-hydroxy-pyrazole-3-carboxylate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
71.2%	at 85℃; for 12h;	4.1.1. 5-methyl-1-(4-((N-methylsulfiiamoyl)methyl)phenyl)-1H-pyrazole-3-carboxylic acid (12a) General procedure: Step 2. To a solution of 8a (118 mg, 1 mmol) and 4-hydrazino-N-methylbenzenemethanesulfonamide hydrochloride (9, 252 mg, 1 mmol) in anhydrous ethanol (10 mL) was stirred at 85 °C overnight. The reaction was allowed to cool to room temperature and concentrated. The crude material was purified by Isolera Biotage LPLC (PE/EA = 30%) to give a mixture of methyl 5-methyl-1-(4-((N-methylsulflamoyl)methyl)phenyl)-1H-pyrazole-3-carboxylate (10a) and ethyl 5-methyl-1-(4-((N-methylsulflamoyl)methyl)phenyl)-1H-pyrazole-3-carboxylate (11a) as a white solid.
71.2%	at 85℃; for 12h;	4.1.1. 5-methyl-1-(4-((N-methylsulfiiamoyl)methyl)phenyl)-1H-pyrazole-3-carboxylic acid (12a) General procedure: Step 2. To a solution of 8a (118 mg, 1 mmol) and 4-hydrazino-N-methylbenzenemethanesulfonamide hydrochloride (9, 252 mg, 1 mmol) in anhydrous ethanol (10 mL) was stirred at 85 °C overnight. The reaction was allowed to cool to room temperature and concentrated. The crude material was purified by Isolera Biotage LPLC (PE/EA = 30%) to give a mixture of methyl 5-methyl-1-(4-((N-methylsulflamoyl)methyl)phenyl)-1H-pyrazole-3-carboxylate (10a) and ethyl 5-methyl-1-(4-((N-methylsulflamoyl)methyl)phenyl)-1H-pyrazole-3-carboxylate (11a) as a white solid.

Reference： [1]Fan, Yan; Fang, Zhen; Guo, Nihong; Guo, Yinping; Li, Linli; Liu, Yang; Mu, Bo; Xia, Anjie; Xiang, Rong; Xiong, Liang; Yang, Shengyong; Yao, Rui; Zhang, Hailin; Zhang, Rong [European Journal of Medicinal Chemistry, 2022, vol. 238]
[2]Fan, Yan; Fang, Zhen; Guo, Nihong; Guo, Yinping; Li, Linli; Liu, Yang; Mu, Bo; Xia, Anjie; Xiang, Rong; Xiong, Liang; Yang, Shengyong; Yao, Rui; Zhang, Hailin; Zhang, Rong [European Journal of Medicinal Chemistry, 2022, vol. 238]

86
[ 328-42-7 ]
[ 64-17-5 ]
[ 2923-56-0 ]
ethyl 5-hydroxy-1-(4-(trifluoromethyl)phenyl)-1H-pyrazole-3-carboxylate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
75.3%	at 85℃; for 12h;	4.1.1. 5-methyl-1-(4-((N-methylsulfiiamoyl)methyl)phenyl)-1H-pyrazole-3-carboxylic acid (12a) General procedure: Step 2. To a solution of 8a (118 mg, 1 mmol) and 4-hydrazino-N-methylbenzenemethanesulfonamide hydrochloride (9, 252 mg, 1 mmol) in anhydrous ethanol (10 mL) was stirred at 85 °C overnight. The reaction was allowed to cool to room temperature and concentrated. The crude material was purified by Isolera Biotage LPLC (PE/EA = 30%) to give a mixture of methyl 5-methyl-1-(4-((N-methylsulflamoyl)methyl)phenyl)-1H-pyrazole-3-carboxylate (10a) and ethyl 5-methyl-1-(4-((N-methylsulflamoyl)methyl)phenyl)-1H-pyrazole-3-carboxylate (11a) as a white solid.
75.3%	at 85℃; for 12h;	4.1.1. 5-methyl-1-(4-((N-methylsulfiiamoyl)methyl)phenyl)-1H-pyrazole-3-carboxylic acid (12a) General procedure: Step 2. To a solution of 8a (118 mg, 1 mmol) and 4-hydrazino-N-methylbenzenemethanesulfonamide hydrochloride (9, 252 mg, 1 mmol) in anhydrous ethanol (10 mL) was stirred at 85 °C overnight. The reaction was allowed to cool to room temperature and concentrated. The crude material was purified by Isolera Biotage LPLC (PE/EA = 30%) to give a mixture of methyl 5-methyl-1-(4-((N-methylsulflamoyl)methyl)phenyl)-1H-pyrazole-3-carboxylate (10a) and ethyl 5-methyl-1-(4-((N-methylsulflamoyl)methyl)phenyl)-1H-pyrazole-3-carboxylate (11a) as a white solid.

Reference： [1]Fan, Yan; Fang, Zhen; Guo, Nihong; Guo, Yinping; Li, Linli; Liu, Yang; Mu, Bo; Xia, Anjie; Xiang, Rong; Xiong, Liang; Yang, Shengyong; Yao, Rui; Zhang, Hailin; Zhang, Rong [European Journal of Medicinal Chemistry, 2022, vol. 238]
[2]Fan, Yan; Fang, Zhen; Guo, Nihong; Guo, Yinping; Li, Linli; Liu, Yang; Mu, Bo; Xia, Anjie; Xiang, Rong; Xiong, Liang; Yang, Shengyong; Yao, Rui; Zhang, Hailin; Zhang, Rong [European Journal of Medicinal Chemistry, 2022, vol. 238]

87
[ 18470-06-9 ]
[ 328-42-7 ]
[ 388089-38-1 ]

Yield	Reaction Conditions	Operation in experiment
	With hydrogenchloride In lithium hydroxide monohydrate at 37℃;	2.2 Synthesis and isolation of DPMv3glc (2) A solution containing Mv3glc 1 (0.18mM)/oxaloacetic acid (molar ratio of 1:10) was prepared in 50mL deionized water solution at pH 2.6 (adjusted with dilute HCl or NaOH). The reaction was carried out at 37°C under constant stirring and the formation of the product was monitored by HPLC-DAD. After maximum formation of the compound, the synthesis reaction was stopped and submitted to liquid-liquid extraction with ethyl acetate to remove the oxaloacetic acid and other organic impurities. The aqueous phase containing 2 was concentrated and purified by flash column chromatography loaded with RP-C18 gel. The product was eluted with 40% (v/v) of aqueous MeOH acidified with 2% HCl. The solvent was removed under vacuum and, the purified compound was freeze-dried and obtained as an orange powder with a 22 % of yield.

Reference： [1]Cruz, Luís; Mateus, Nuno; Monteiro, Marta; Sampaio-Dias, Ivo E.; de Freitas, Victor [Food Chemistry, 2022, vol. 393]

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. :	328-42-7	MDL No. :	MFCD00002592
Formula :	C₄H₄O₅	Boiling Point :	-
Linear Structure Formula :	-	InChI Key :	KHPXUQMNIQBQEV-UHFFFAOYSA-N
M.W :	132.07	Pubchem ID :	970
Synonyms :	Oxalacetic Acid;2-Oxosuccinic acid;OAA;NSC 77688;NSC 284205;Ketosuccinic acid

Num. heavy atoms :	9
Num. arom. heavy atoms :	0
Fraction Csp3 :	0.25
Num. rotatable bonds :	3
Num. H-bond acceptors :	5.0
Num. H-bond donors :	2.0
Molar Refractivity :	25.09
TPSA :	91.67 Å²

GI absorption :	High
BBB permeant :	No
P-gp substrate :	No
CYP1A2 inhibitor :	No
CYP2C19 inhibitor :	No
CYP2C9 inhibitor :	No
CYP2D6 inhibitor :	No
CYP3A4 inhibitor :	No
Log Kp (skin permeation) :	-7.55 cm/s

[ CAS No. 328-42-7 ] {[proInfo.proName]}

Quality Control of [ 328-42-7 ]

Related Doc. of [ 328-42-7 ]

Product Details of [ 328-42-7 ]

Calculated chemistry of [ 328-42-7 ]

Physicochemical Properties

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[ 328-42-7 ] Synthesis Path-Upstream 1~13

[ 328-42-7 ] Synthesis Path-Downstream 1~87

Related Functional Groups of
[ 328-42-7 ]

Aliphatic Chain Hydrocarbons

Ketones

Carboxylic Acids

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Log Po/w (iLOGP) :	-0.48
Log Po/w (XLOGP3) :	-0.63
Log Po/w (WLOGP) :	-0.89
Log Po/w (MLOGP) :	-1.47
Log Po/w (SILICOS-IT) :	-0.93
Consensus Log Po/w :	-0.88

Lipinski :	0.0
Ghose :	None
Veber :	0.0
Egan :	0.0
Muegge :	2.0
Bioavailability Score :	0.56

Log S (ESOL) :	-0.06
Solubility :	114.0 mg/ml ; 0.863 mol/l
Class :	Very soluble
Log S (Ali) :	-0.82
Solubility :	19.9 mg/ml ; 0.15 mol/l
Class :	Very soluble
Log S (SILICOS-IT) :	1.05
Solubility :	1500.0 mg/ml ; 11.3 mol/l
Class :	Soluble

PAINS :	0.0 alert
Brenk :	2.0 alert
Leadlikeness :	1.0
Synthetic accessibility :	1.49

Signal Word:	Danger	Class:	8
Precautionary Statements:	P280-P305+P351+P338-P310	UN#:	3261
Hazard Statements:	H290-H314	Packing Group:	Ⅱ
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

[ CAS No. 328-42-7 ] {[proInfo.proName]}

Quality Control of [ 328-42-7 ]

Related Doc. of [ 328-42-7 ]

Product Details of [ 328-42-7 ]

Calculated chemistry of [ 328-42-7 ]

Physicochemical Properties

Pharmacokinetics

Lipophilicity

Druglikeness

Water Solubility

Medicinal Chemistry

Safety of [ 328-42-7 ]

Application In Synthesis of [ 328-42-7 ]

[ 328-42-7 ] Synthesis Path-Upstream 1~13

[ 328-42-7 ] Synthesis Path-Downstream 1~87

Related Functional Groups of [ 328-42-7 ]

Aliphatic Chain Hydrocarbons

Ketones

Carboxylic Acids

Precautionary Statements-General

Prevention

Response

Storage

Disposal

Physical hazards

Health hazards

Environmental hazards

Inquiry

Related Functional Groups of
[ 328-42-7 ]