Name: 6068-72-0|4-Cyanobenzoyl chloride|98%
Brand: Ambeed
SKU: A429652
Price: 14.0 USD
Availability: InStock
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1
[ 619-65-8 ]
[ 6068-72-0 ]

Yield	Reaction Conditions	Operation in experiment
98%		After dry nitrogen gas was introduced to the reaction mixture for one hour, acetonitrile was removed under ambient pressure, and was further removed under reduced pressure through distillation, to thereby obtain 16.2 g of p-cyanobenzoyl chloride (yield 98%, based on p-cyanobenzoic acid). The p-cyanobenzoyl chloride obtained had a purity of 99%.
98%	With thionyl chloride; N,N-dimethyl-formamide; for 1.5h;Reflux;	<strong>[619-65-8]4-Cyanobenzoic acid</strong> (5) (30.00 g,203.90 mmol) was added to thionyl chloride (29.11 g, 244.68 mmol) in batches with magnetic stirring. Then, three drops of DMF were added to the solution. The reaction mixture was heated to reflux and stirred for 1.5 h (monitored by TLC). The solution was distilled at 235 C to yield a white solid; yield 98% (5.50 g); m.p. 67.2-68.2 C; 1H NMR (600 MHz,DMSO-d6): delta 8.06 (d, J = 7.8 Hz, 2 H), 7.96 (d, J = 7.8 Hz, 2 H). 13C NMR(151 MHz, DMSO-d6): delta 165.9, 134.7, 132.6, 129.9, 118.1, 115.1. IR (KBr,numax/cm-1): 3101, 3051, 2229, 1772, 1739, 1597, 1401, 1287, 1211, 1167,896, 851, 634. HR-MS (ESI) m/z: [M+H]+ calcd for C8H4ClNO+H+166.0053; found 166.0054.
96%		After dry nitrogen gas was introduced to the reaction mixture for one hour, the mixture was distilled under reduced pressure, to thereby obtain 31.8 g of p-cyanobenzoyl chloride (yield 96%, based on p-cyanobenzoic acid). The p-cyanobenzoyl chloride obtained had a purity of 99% or more.

93.3%	With oxalyl dichloride; In dichloromethane; at 0 - 25℃; for 3h;	<strong>[619-65-8]4-Cyanobenzoic acid</strong> (2.0 g, 13.6 mmol) was dissolved in dichloromethane (20 mL) at 0 C and oxalyl chloride (3.58, 27.611111101) was slowly added dropwise with the addition dropwise to 25 C : For 3 hours and concentrated to give the product (2.18, 93.3% yield)
76%	With phosphorus trichloride; In acetonitrile; at 80℃; for 24h;Inert atmosphere;	In the reaction flask, p-cyanobenzoic acid (1 mmol) was added.Adding phosphorus trichloride under a nitrogen atmosphere(0.333 mmol) and acetonitrile (1.0 mL) at 80 C,The reaction was stirred for 24 hours. After the reaction is over, the bottle wall is precipitated in a large amount.Insoluble solids. The reaction solution was filtered to dry a solvent, and the concentrated reaction liquid was collected at a vacuum of 1 to 10 mmHg to collect a fraction of 100 to 120 C. The product obtained was a white solid yield of 76%.
71%	With oxalyl dichloride; In dichloromethane; at 0 - 25℃; for 0.5h;	General procedure: The purchased acids (14.40 mmol) was added into 5 mL DCM andcooled to 0 C. After the oxalyl chloride (1.50 mL, 17.30 mmol) wasadded drop wise, the mixture was removed to room temperature andstirred for 30 min. The solvent was evaporated for use.To a cooled solution of 5 (3.70 g, 17.30 mmol) in 20 mL DCM wasadded Et3N (3.00 mL, 21.60 mmol) then the prepared chloride wasadded drop wise. The mixture was stirred at room temperature for 1 h.The solvent was evaporated under reduced pressure and the residuewas purification by column chromatography with dichloromethane/methanol as eluent on silica gel to give the derivatives7a-7h.
	With oxalyl dichloride;N,N-dimethyl-formamide; In dichloromethane; at 20℃; for 0.25h;	To a suspension of 4-cyano-benzoic acid (1 g) in DCM (0.5 M) was added oxalyl chloride (2.5 eq) and a few drops of DMF. The reaction mixture was stirred at RT for 15 min. The solvent was evaporated. The residue was dissolved in DCM (0.5 M). DIEA (1.2 eq) and 4-amino-pyridine (640 mg, leq) were added. After completion of the reaction (2 hours), the solvent was removed under vacuum. The residue was purified by flash chromatography (DCM/MeOH 95/5, Rf=0. 10), yielding a pale yellow powder (42% yield). 1H NMR (300 MHz, DMSO-d6): 7.75 ppm (dd, 2H, J= 1.5 Hz & 4.8 Hz); 8.06 ppm (m, 4H); 8.48 ppm (dd, 2H, J= 1.5 & 4.8Hz) ; 10.80 ppm (s, 1H) ; mp: 200.2-202. 4C.
	In thionyl chloride;	(a) 1st Stage--Preparation of 4-Cyanobenzoyl chloride <strong>[619-65-8]4-Cyanobenzoic acid</strong> (1.0 g, 6.8 mmol) was suspended in thionyl chloride (5 ml) and refluxed for 2 hours. The reaction mixture was cooled and the solvent was removed under water pressure to give a cream solid, which was dried in vacuo, (1.04 g, 6.3 mmol, 92%).
	With thionyl chloride; In hexane; dichloromethane; for 1h;Heating / reflux;	EXAMPLE 44 4-(5H,11H-Pyrrolo[2,1-c][1,4]benzodiazepine-10-carbonyl)-benzonitrile <strong>[619-65-8]4-Cyanobenzoic acid</strong> (5.0 g) and thionyl chloride (5.0 ml) were heated on a steam bath for one hour, and all of the volatiles were removed at reduced pressure.. hexane was added and the crude crystalline acid chloride (5.30 g) was recovered by filtration, and used without further purification. To a reaction mixture of 10,11-dihydro-5H-pyrrolo[2,1-c][1,4]-benzodiazepine (3.68 g), dichloromethane (100 ml), and diisopropylethylamine (2.80 g) was added 4-cyanobenzoyl chloride (2.97 g).. After remaining at room temperature for 18 hours, the reaction mixture was washed with water and saturated aqueous sodium bicarbonate solution.. The dichloromethane solution was dried over anhydrous sodium sulfate and filtered through a short column of hydrous sodium magnesium silicate and further eluted with several volumes of dichloromethane.. The combined organic phase was concentrated on a hot plate with the gradual addition of hexane until crystallization occurred.. After cooling, the crystals were collected by filtration to yield the title compound (5.05) g, m.p. 184-186 C.
	With thionyl chloride; at 100℃; for 1h;	<strong>[619-65-8]4-Cyanobenzoic acid</strong> (5.0 g) and thionyl chloride (5.0 ml) were heated on a steam bath for one hour, and all of the volatiles were removed at reduced pressure. Hexane was added and the crude crystalline acid chloride (5.30 g) was recovered by filtration, and used without further purification.
	With thionyl chloride; for 8h;Reflux;	To a round-bottomed flask was added 4-cyanobenzoic acid (330 mg, 2.2 mmol), 10 mL of thionyl chloride, and the mixture was refluxed for 8 h. After cooling, the excess of thionyl chloride was removed at reduced pressure to give the 4-fluorobenzoyl chloride, which was added to a solution of compound 7 (790 mg, 2 mmol) in 10 mL of pyridine. The reaction mixture was stirred for 2 h at 90 C and then poured into water. The solid was filtered and crystallized from ethanol to give 8a as white crystals; yield, 76%.
	With thionyl chloride; for 2h;Heating;	A mixture of 2-chlorobenzoic acid (1b) (0.61 g, 3.92 mmol) and thionyl chloride (1 mL) was heated for 2 h. The excess of thionyl chloride was recovered under reduced pressure and the residue so obtained was dissolved in dry dioxane (1 mL). The solution was then dropwise added to mixture of 2-amino-4,5-dimethoxybenzamide (2) (0.7 g, 3.57 mmol) and TEA (1.2 mL, 8.92 mmol) in dry dioxane (2 mL) at 10 C. The reaction mixture was stirred at rt for another 1 h and quenched into cold water (50 mL). The precipitate formed was filtered, washed with water and dried to obtain compound 3b (0.85 g, 71%): mp 213-215 C (dec.); IR (KBr,): 3406, 3305, 1658, 1645, 1612, 1525, 1253, 1078 and 1039 cm-1.
	With oxalyl dichloride; N,N-dimethyl-formamide; In dichloromethane; at 20℃;	General procedure: To a solution of ethyl 4-aminobenzoate (1 equiv) in dichloromethane was added dropwise a solution of substituted benzoyl chloride (prepared from substituted benzoic acid (1 equiv) and oxalyl dichloride (1.2 equiv) in the presence of DMF as the catalyst) and triethylamine (1 equiv). The reaction mixture was stirred for 12 h at room temperature and concentrated in vacuo. The residue was dissolved in ethyl acetate. The resulting organic phase was washed with 5% sodium bicarbonate, 5% hydrochloric acid and water in sequence, dried over Na2SO4, and concentrated to give compound 18, which was hydrolysis with aqueous sodium hydroxide (1 M, 5 mL) in ethanol (5 mL) by stirring at 60 oC. Upon completion, as determined by TLC, the solvent was evaporated. The residue was dissolved in water (20 mL) and subjected to acidification with diluted hydrochloric acid. The precipitate was filtrated and the filter cake was washed with water and dried to yield 19. In a similar but simplified procedure, 20 were achieved by direct reaction of substituted benzoyl chloride with amino benzoic acid.
	With thionyl chloride; In dichloromethane; for 4h;Reflux;	Step 1 4-cyanobenzoyl chloride To a solution of 4-cyanobenzoic acid (5 g, 33.98 mmol, 1.00 equiv) in dichloromethane (50 mL) was added thionyl chloride (25 mL) dropwise with stirring. The resulting solution was refluxed for 4 h. The reaction mixture was cooled to room temperature and concentrated under vacuum to give 3 g of crude 4-cyanobenzoyl chloride as a brown solid. The crude was used in the next step without further purification.
	With oxalyl dichloride; N,N-dimethyl-formamide; In dichloromethane; at 0℃;Inert atmosphere; Schlenk technique;	General procedure: To a solution of carboxylic acid (5 mmol) in CH2Cl2 (10 mL) were added oxalyl chloride (0.5 mL, 6 mmol, 1.2 equiv.) and DMF (two drops) at 0 C. The mixture was stirred until gas evolution stopped. Then it was concentrated under reduced pressure, washed with dichloromethane and concentrated again. The crude acyl chloride was used directly in the next step.
	With oxalyl dichloride; N,N-dimethyl-formamide; In dichloromethane; at 0 - 27℃;Inert atmosphere;	Under nitrogen in 250mL of dried two-necked flask cyano-benzoic acid (15.02g, 100.00mmol), in dry dichloromethane (150 mL), stirred, insoluble in the majority of cyano acid and the reaction transferred to a low temperature cooling tank. Cooling down to 0 ~ 5 dropwise oxalyl chloride (15.23g, 120.00mmol), after the completion of the dropwise addition, the dropwise addition of anhydrous N, N- dimethylformamide (0.2OmL), after the completion of the dropwise addition, the reaction out of the low-temperature cooling tank. Warmed to 23 ~ 27 , the reaction 24 ~ 28h, until completely dissolved after cyano acid clearance, the reaction solvent was evaporated under reduced pressure, steam Bi, a yellow solid (16.73g, 101.03%)
	With thionyl chloride; at 80℃; for 24h;	General procedure: To an appropriately substituted benzoic acid (10.0 mmol) in around-bottomed flask was added excess thionyl chloride (15 ml). The mixture was gently stirred and refluxed at 80C in an oil bath for 24 h. After cooling the reaction mixture to room temperature, excess thionyl chloride was evaporated leaving a pale yellow benzoyl chloride residue which was dissolved in distilled acetonitrile (5 ml) and cautiously added to an ice-cold mixture of 2-amino-6-bromo-pyridine (1.6 g, 9.2 mmol) and pyridine (3 ml) in acetonitrile (15 ml). The mixture was stirred at 0C for 30 min, warmed to room temperature and stirred for 4 h. Solvent was removed under reduced pressure and the residue was dissolved in dichloromethane (20 ml) and washed successively with aqueous saturated NaHCO3 (2x10 ml), saturated brine solution (10 ml) and distilled water (2x10 ml) and then dried over anhydrous MgSO4 or Na2SO4. The solvent was removed in vacuo and the crude mixture purified by flash silica gel column chromatography, eluting with 3-5% EtOAc/hexane to give the desired product.
	With thionyl chloride; In toluene; for 2h;Reflux;	General procedure: To the carboxylic acid (4.98 mmol), PhMe (25 mL) was added followed by SOCl2 (1.1 mL, 14.92 mmol). The suspension was heated to reflux for 2 h before the solvent was removed under reduced pressure. The mixture was dissolved in dry DCM (10 mL) before K2CO3 (1.5 g, 10.85 mmol) was added and morpholine amine (1.5 mL) was added drop wise at 0 C. The cooling bath was removed after 30 min and stirring was continued at rt overnight. The mixture was filtered, the solvent evaporated and the crude material was purified by column chromatography.
	With oxalyl dichloride; N,N-dimethyl-formamide; In dichloromethane; at 0 - 20℃; for 3h;	General procedure: To a 100 mL three-necked flask, acid (20 mmol), DMF (3 drops), and anhydrous CH2Cl2 (30 mL)were added. Oxalyl chloride (40 mmol, 2 equiv) was added dropwise at 0C resulting in vigorousbubbling. The mixture was stirred for 3 h at room temperature, and the solvent was then removedin vacuo. The resulting acid chloride was used immediately without further purification. The acidcholoride was then re-dissolved in 25 mL dry CH2Cl2 and added dropwise to a 30 mL dry CH2Cl2solution containing amine (24 mmol) and Et3N (30 mmol) at 0 C. After stirring for 6h at roomtemperature, the resulting mixture was washed with brine, dried over Na2SO4, filtered andconcentrated under reduced pressure. The residue was purified by flash chromatography to give thedesired product.
	With oxalyl dichloride; N,N-dimethyl-formamide; In dichloromethane; at 0℃;Inert atmosphere; Schlenk technique;	General procedure: To a solution of carboxylic acid (5 mmol) in CH2Cl2 (10 mL) were added oxalyl chloride (0.5 mL, 6 mmol, 1.2 equiv.) and DMF (two drops) at 0C. The mixture was stirred until gas evolution stopped. Then it was concentrated under reduced pressure, washed with dichloromethane and concentrated again. The crude acyl chloride wasused directly in the next step.
	With thionyl chloride; In toluene; for 2h;Reflux;	4-cyanobenzoic acid (0.80 g, 5.38 mmol), toluene (6 mL), and dichloromethane (3.2 g, 26.9 mmol) were added to the reaction mixture, and the mixture was stirred under reflux for 2 h. , the concentrated residue is dissolved in tetrahydrofuran(3mL) to be used. Methyl 2-fluoro-(3-(cyclopropylmethyl)amino)benzoate (1.0 g, 4.48 mmol) was dissolved in tetrahydrofuran (6 mL), triethylamine (0.74 g, 5.38 mmol) A solution of cyanobenzoyl chloride in tetrahydrofuran was stirred at room temperature for 4 h.The reaction was terminated when TLC was monitored until the reaction was no longer carried out. Water (20 mL) was added to the reaction mixture, and the mixture was evaporated, evaporated, evaporated, evaporated.For petroleum ether: ethyl acetate = 3:1), a colorless liquid productMethyl 2-fluoro-3-(4-cyano-N-(cyclopropylmethyl)benzamide)benzoate (1.40 g, yield 88.83%).
	With oxalyl dichloride; N,N-dimethyl-formamide; In dichloromethane; at 20℃; for 2h;	General procedure: One drop of dry N,N-dimethyl formamide and oxalyl chloride (0.62 g, 4.9 mmol) were addeddropwise to a solution of 4-methoxybenzoic acid (0.50 g, 3.3 mmol) in dry CH2Cl2 (20 mL). The reactionmixture was stirred at room temperature for 2 h, and then distilled in vacuo to give the crude acylchloride, which was dissolved in dry CH2Cl2 (10 mL). Dry triethylamine (0.40 g, 3.9 mmol) was addedto a solution of benzylamine (0.35 g, 3.3 mmol) in dry CH2Cl2 (20 mL). The reaction mixture wascooled to 0 C, and the acyl chloride solution was added dropwise. After stirring at 20-25 C for 4 h,the reaction mixture was distilled in vacuo, and washed with a 10% solution of NaOH and water,and dried. Silica gel column chromatography (hexane/ethyl acetate) afforded I-1 as a white powder(0.75 g, 94.8% yield).

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2
[ 96-13-9 ]
[ 6068-72-0 ]
[ 99851-98-6 ]

Reference： [1]Journal of the American Pharmaceutical Association (1961),1952,vol. 41,p. 202 - 204

3
[ 6068-72-0 ]
[ 100-49-2 ]
4-cyano-benzoic acid cyclohexylmethyl ester [ No CAS ]

Reference： [1]Journal of the American Pharmaceutical Association (1961),1953,vol. 42,p. 371 - 373

4
[ 6068-72-0 ]
[ 873-74-5 ]
[ 132640-25-6 ]

Yield	Reaction Conditions	Operation in experiment
94%	With triethylamine In tetrahydrofuran 1.) 10 deg C, 1 h, 2.) RT, 3 h;
91%	With triethylamine In tetrahydrofuran at 0 - 20℃; for 24h; Inert atmosphere;	N-(4-Cyanophenyl)-4-cyanobenzamide (23) To a mixture of 4-aminobenzonitrile (237 mg, 2 mmol) and TEA (505 mg, 5 mmol) in THF (20 mL) at 0 C and under Ar was added 4-cyanobenzoyl chloride (398 mg, 2.4 mmol). After it was stirred at rt for 24 h, the reaction mixture was concentrated and diluted with brine (50 mL). The resulting precipitate was collected by filtration and recrystallized from water to give23(452 mg, 91%) as a white solid. mp 258-260 C. (lit.8mp 267 °C)1H NMR (500 MHz, DMSO-d6)7.85 (d,J= 8.3 Hz, 2H), 7.99 (d,J= 7.8 Hz, 2H), 8.06 (d,J= 8.3 Hz, 2H), 8.12 (d,J= 7.4 Hz, 2H), 10.85 (s, 1H);13C NMR (125.7 MHz, DMSO-d6)106.01, 114.43, 118.40, 119.14, 120.50, 128.87, 132.70, 133.36, 138.53, 143.22, 164.98.
	With pyridine

With triethylamine In tetrahydrofuran

12 N-(4-cyanophenyl)-4-cyanobenzamide EXAMPLE 12 N-(4-cyanophenyl)-4-cyanobenzamide 13.1 g (0.13 moles) of triethylamine were added to a solution of 14.2 g (0.12 moles) of 4-aminobenzonitrile in 100 ml of tetrahydrofuran and the temperature was then kept at about 5° C. and 20 g (0.12 moles) of 4-cyanobenzoyl chloride were added dropwise. The mixture was left to react for 12 h under agitation. The solvent was evaporated, the residue was taken up with H2 O and the precipitate formed was filtered.

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[2]Dong, Yuxiang; Wang, Xiaofang; Cal, Monica; Kaiser, Marcel; Vennerstrom, Jonathan L. [Bioorganic and Medicinal Chemistry Letters, 2014, vol. 24, # 3, p. 944 - 948]
[3]Ashley et al. [Journal of the Chemical Society, 1942, p. 103,107]
[4]Current Patent Assignee: VIATRIS INC - US5232937, 1993, A

5
[ 1128-00-3 ]
[ 6068-72-0 ]
[ 55788-88-0 ]

Reference： [1]Journal of Medicinal Chemistry,1975,vol. 18,p. 509 - 513

6
[ 67198-21-4 ]
[ 6068-72-0 ]
4-Cyano-N-((1S,2S)-2-dimethylamino-cyclohexyl)-benzamide [ No CAS ]

Reference： [1]Patent: BE860727,1978,
Patent: DE2749984,1978,
Chem.Abstr.,1978,vol. 89

7
[ 33544-42-2 ]
[ 6068-72-0 ]
4-Cyano-benzoic acid N'-(3-nitro-pyridin-4-yl)-hydrazide; hydrochloride [ No CAS ]

Reference： [1]Journal of Medicinal Chemistry,1989,vol. 32,p. 2474 - 2485

8
[ 75-75-2 ]
[ 6068-72-0 ]
[ 82957-06-0 ]
[ 82955-96-2 ]

Reference： [1]Chemical and Pharmaceutical Bulletin,1985,vol. 33,p. 1458 - 1471

9
[ 2443-62-1 ]
[ 6068-72-0 ]
4-Cyano-benzoic acid N'-hexanoyl-hydrazide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	In pyridine 1.) 0-5 deg C, 45 min., 2.) room temp., 45 min., 3.) 80 deg C, 3 h;

Reference： [1]Dimitrowa, K.; Hauschild, J.; Zaschke, H.; Schubert, H. [Journal fur praktische Chemie (Leipzig 1954), 1980, vol. 322, # 6, p. 933 - 944]

10
[ 83-40-9 ]
[ 6068-72-0 ]
[ 92524-85-1 ]

Reference： [1]Journal of Medicinal Chemistry,1985,vol. 28,p. 143 - 146

11
[ 20059-73-8 ]
[ 6068-72-0 ]
[ 122892-82-4 ]

Reference： [1]Chemical and Pharmaceutical Bulletin,1992,vol. 40,p. 202 - 211

12
[ 5434-21-9 ]
[ 6068-72-0 ]
[ 144907-46-0 ]

Reference： [1]Journal of Medicinal Chemistry,1992,vol. 35,p. 3633 - 3640

13
[ 4714-62-9 ]
[ 6068-72-0 ]
[ 143330-45-4 ]

Reference： [1]Journal of Medicinal Chemistry,1992,vol. 35,p. 3633 - 3640

14
[ 6068-72-0 ]
[ 99-05-8 ]
[ 135322-12-2 ]

Yield	Reaction Conditions	Operation in experiment
83%	With dmap In N,N-dimethyl acetamide at 20℃; for 24h; Inert atmosphere;	N-(4-Cyanophenyl)-3-[(4-cyanobenzoyl)amino]benzamide Step 1.To a mixture of 3-aminobenzoic acid (1.37 g, 10 mmol) and DMAP (50 mg, 0.4 mmol) in DMA (30 mL) under Ar was added 4-cyanobenzoyl chloride (1.66 g, 10 mmol). After it was stirred at rt for 24 h, the reaction was quenched with brine (100 mL). The resulting precipitate was collected by filtration and recrystallized from CH3CN:water (1:1) to give 3-[(4-cyanobenzoyl)amino]benzoic acid(2.21 g, 83%) as a white solid. mp 271-273 C.1H NMR (500 MHz, DMSO-d6)7.49 (t,J= 7.8 Hz, 1H), 7.70 (d,J= 7.8 Hz, 1H), 8.03 (d,J= 8.3 Hz, 3H), 8.13 (d,J= 8.3 Hz, 2H), 8.41 (s, 1H), 10.64 (s, 1H), 13.00 (s, 1H);13C NMR (125.7 MHz, DMSO-d6)114.17, 118.48, 121.37, 124.64, 125.03, 128.75, 129.17, 131.47, 132.68, 138.83, 139.18, 164.47, 167.28.
63%	With sodium hydrogencarbonate In tetrahydrofuran at 0℃; for 2h;	3-(4-cyanobenzamido)benzoic acid 3-Aminobenzoic acid (230 mg; 1.68 mmol) was dissolved in THF (1.2 mL) and NaHCCb saturated solution (1.2 mL), to it 4-cyanobenzoyl chloride (277 mg; 1.68 mmol) was added at 0 °C. Reaction stirred for 2 hours, pH adjusted to 1, precipitate collected by filtration, washed with HC1 1 N, triturated with Et20 and dried at high vacuum to give 280 mg of a solid (1.05 mmol; y= 63%). 1H NMR (500 MHz, DMSO) δ 13.02 (br, 1H), 10.67 (s, 1H), 8.42 (t, J= 1.8 Hz, 1H), 8.14 (d, J= 8.4 Hz, 2H), 8.04 (d, J= 8.4 Hz, 3H), 7.71 (d, J= 7.8 Hz, 1H), 7.50 (t, J= 7.9 Hz, 1H). 13C NMR (126 MHz, DMSO) δ 167.1, 164.3, 139.0, 138.6, 132.5, 131.3, 129.0, 128.6, 124.8, 124.5, 121.2, 118.3, 114.0.HRMS (ESI) calculated for C15H9N203 (M-H) 265.0619, found 265.0606.
	With triethylamine In tetrahydrofuran 1.) 10 deg C, 1 h, 2.) RT, 3 h;

Reference： [1]Dong, Yuxiang; Wang, Xiaofang; Cal, Monica; Kaiser, Marcel; Vennerstrom, Jonathan L. [Bioorganic and Medicinal Chemistry Letters, 2014, vol. 24, # 3, p. 944 - 948]
[2]Current Patent Assignee: Helmholtz Association - WO2019/38405, 2019, A1 Location in patent: Page/Page column 122
[3]Makovec; Peris; Revel; Giovanetti; Redaelli; Rovati [Journal of Medicinal Chemistry, 1992, vol. 35, # 20, p. 3633 - 3640]

15
[ 6068-72-0 ]
[ 150-13-0 ]
[ 143330-23-8 ]

Yield	Reaction Conditions	Operation in experiment
85%	With dmap In N,N-dimethyl acetamide at 20℃; for 24h; Inert atmosphere;	N-(4-Cyanophenyl)-4-[(4-cyanobenzoyl)amino]benzamide Step 1.To a mixture of 4-aminobenzoic acid (1.37 g, 10 mmol) and DMAP (50 mg, 0.4 mmol) in DMA (30 mL) under Ar was added 4-cyanobenzoyl chloride (1.66 g, 10 mmol). After it was stirred at rt for 24 h, the reaction was quenched with brine (100 mL). The resulting precipitate was collected by filtration and recrystallized from CH3CN:water (1:1) to give 4-[(4-cyanobenzoyl)amino]benzoic acid(2.27 g, 85%) as a white solid. Mp 243-245 C.1H NMR (500 MHz, DMSO-d6)7.90 (d,J= 8.8 Hz, 2H), 7.95 (d,J= 8.8 Hz, 2H), 8.04 (d,J= 8.3 Hz, 2H), 8.11 (d,J= 8.3 Hz, 2H), 10.73 (s, 1H), 12.77 (s, 1H);13C NMR (125.7 MHz, DMSO-d6)114.26, 118.45, 119.82, 126.12, 128.84, 130.46, 132.69, 138.83, 143.01, 164.78, 167.06.
72%	With sodium hydrogencarbonate In tetrahydrofuran at 0℃; for 2h;	4-(4-cyanobenzamido)benzoic acid 4-Aminobenzoic acid (213 mg; 1.56 mmol) was dissolved in THF (1.2 mL) and NaHCO3 saturated solution (1.2 mL), to it 4-cyanobenzoyl chloride (285 mg; 1.73 mmol) was added at 0 °C. Reaction stirred for 2 hours, precipitate collected by filtration, washed with water and triturated with Et20, dried at high vacuum to give 300 mg of a solid (1.13 mmol; y= 72%). 1H NMR (500 MHz, DMSO) δ 12.81 (br, 1H), 10.77 (s, 1H), 8.14 - 8.1 1 (m, 2H), 8.07 - 8.03 (m, 2H), 7.98 - 7.94 (m, 2H), 7.94 - 7.90 (m, 2H).1 3C NMR (126 MHz, DMSO) δ 167.4, 165.1 , 143.3, 139.1, 133.0, 130.8, 129.1, 126.4, 120.1, 118.8, 114.6. HRMS (ESI) calculated for C15H9N203 (M-H) 265.0619, found 265.0622.
	With triethylamine In tetrahydrofuran 1.) 10 deg C, 1 h, 2.) RT, 3 h;

Reference： [1]Dong, Yuxiang; Wang, Xiaofang; Cal, Monica; Kaiser, Marcel; Vennerstrom, Jonathan L. [Bioorganic and Medicinal Chemistry Letters, 2014, vol. 24, # 3, p. 944 - 948]
[2]Current Patent Assignee: Helmholtz Association - WO2019/38405, 2019, A1 Location in patent: Page/Page column 121-122
[3]Makovec; Peris; Revel; Giovanetti; Redaelli; Rovati [Journal of Medicinal Chemistry, 1992, vol. 35, # 20, p. 3633 - 3640]

16
[ 6068-72-0 ]
[ 67198-26-9 ]
[ 67579-77-5 ]

Yield	Reaction Conditions	Operation in experiment
	With triethylamine In diethyl ether for 17h; Ambient temperature;

Reference： [1]Cheney; Szmuszkovicz; Lahti; Zichi [Journal of Medicinal Chemistry, 1985, vol. 28, # 12, p. 1853 - 1864]

17
[ 6068-72-0 ]
[ 108-88-3 ]
[ 35776-95-5 ]

Reference： [1]Canadian Journal of Chemistry,1980,vol. 58,p. 2537 - 2549
[2]Pharmazie,1976,vol. 31,p. 354 - 360

18
[ 40483-47-4 ]
[ 6068-72-0 ]
4-Cyano-N-(5-methyl-[1,2,4]oxadiazol-3-yl)-benzamide [ No CAS ]

Reference： [1]Tetrahedron,1995,vol. 51,p. 5133 - 5142

19
[ 6068-72-0 ]
[ 18293-54-4 ]
[ 21204-67-1 ]
(E)-3-(4-Cyano-phenyl)-3-[1,2,4]triazol-1-yl-acrylic acid methyl ester [ No CAS ]
(Z)-3-(4-Cyano-phenyl)-3-[1,2,4]triazol-1-yl-acrylic acid methyl ester [ No CAS ]

Reference： [1]Tetrahedron Letters,1996,vol. 37,p. 7249 - 7250

20
[ 6068-72-0 ]
[ 619-05-6 ]
[ 175401-95-3 ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,1996,vol. 6,p. 339 - 344

21
[ 129112-26-1 ]
[ 6068-72-0 ]
1,2-bis(4'-cyanobenzoyl)benzene [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With chloro-trimethyl-silane; 2-chlorophenylzinc iodide; zinc 1.) 1,1,3,3-tetramethylurea, r.t., 0.5 h; 2.) 60 deg C, 3 h; 3.) 1,1,3,3-tetramethylurea, 40 deg C, 6 h; Yield given. Multistep reaction;

Reference： [1]Amano, Masayuki; Saiga, Akihiro; Ikegami, Ryo; Ogata, Takeshi; Takagi, Kentaro [Tetrahedron Letters, 1998, vol. 39, # 47, p. 8667 - 8668]

22
[ 1885-32-1 ]
[ 6068-72-0 ]
[ 220115-22-0 ]

Reference： [1]Journal of Medicinal Chemistry,1998,vol. 41,p. 5247 - 5256

23
[ 1885-32-1 ]
[ 6068-72-0 ]
2-(4-Cyano-benzoylamino)-3-methyl-benzamide [ No CAS ]

Reference： [1]Journal of Medicinal Chemistry,1998,vol. 41,p. 5247 - 5256

24
[ 4877-80-9 ]
[ 6068-72-0 ]
C₆₆H₃₀N₆O₁₂ [ No CAS ]

Reference： [1]Physical Chemistry Chemical Physics,1999,vol. 1,p. 1757 - 1760

25
[ 6281-32-9 ]
[ 6068-72-0 ]
[ 274250-96-3 ]

Reference： [1]Tetrahedron,2000,vol. 56,p. 2239 - 2246

26
[ 6638-79-5 ]
[ 6068-72-0 ]
[ 116332-64-0 ]

Yield	Reaction Conditions	Operation in experiment
88%	With potassium carbonate; In water; acetonitrile; at 20℃; for 2h;	The method of Faul et al. was used. To a suspension of N,O-dimethylhydroxyamine hydrochloride (7.07 g, 72.5 mmol) and K2C03 (10.0 g, 72.5 mmol) in ACN (100 mL) and water (50 mL) was added 4-cyanobenzoyl chloride (27) (8.00 g, 48.3 mmol), and the reaction was stirred for 2 h at room temperature. The reaction solution was poured into water (50 mL) and extracted with ethyl acetate. The combined organic layers were washed with brine, dried over sodium sulfate, and concentrated in vacuo to give a crude solid that was purified by column chromatography (250 mL Si02, hexanesrethyl acetate 45:55 to 1 : 1) to give 28 (8.12 g, 88%) as a white crystalline solid: ? NMR (400 MHz, CDC13) ? 7.76 (d, J= 8.4, 2H), 7.69 (d, J= 8.4, 2H), 3.50 (s, 3H), 3.36(s, 3H); 13C NMR (100.6 MHz, CDC13) ? 167.8, 138.2, 131.8, 128.7, 118.1, 114.0, 61.2, 33.0; GC-MS (M)+ calcd for C10H10N2O2 190.0742, found 190.0739.

Reference： [1]Patent: WO2013/40227,2013,A2 .Location in patent: Page/Page column 27; 28
[2]Journal of Medicinal Chemistry,2013,vol. 56,p. 8432 - 8454
[3]Journal of Organic Chemistry,2001,vol. 66,p. 5772 - 5782
[4]Journal of Medicinal Chemistry,2008,vol. 51,p. 6138 - 6149
[5]Chemistry - A European Journal,2019,vol. 25,p. 9415 - 9418
[6]Journal of Organic Chemistry,2003,vol. 68,p. 5500 - 5511
[7]European Journal of Organic Chemistry,2013,p. 4918 - 4932

27
[ 6068-72-0 ]
[ 157023-34-2 ]
[ 366022-97-1 ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2001,vol. 11,p. 1629 - 1633

28
[ 6068-72-0 ]
[ 162167-97-7 ]
3-[(4-cyano-benzoylamino)-methyl]-piperidine-1-carboxylic acid tert-butyl ester [ No CAS ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2001,vol. 11,p. 2325 - 2330

29
[ 6068-72-0 ]
[ 51856-79-2 ]
[ 617721-38-7 ]

Yield	Reaction Conditions	Operation in experiment
	at 105℃; for 22.5h;	4-Cyanobenzoyl chloride (14.61 g, 88.2 mmol) was suspended in 75 mL in a 3-neck flask. Methyl-N-methyl-2-pyrroleacetate (11.0 mL, 76.4 mmol) was added to the reaction. The flask was equipped with a reflux condenser and a nitrogen bubbler. Nitrogen was gently bubbled through the reaction as it was heated at 105C for 22.5 hours. The reaction was then diluted with 50 mL toluene and poured into a solution of 50 mL 3- (diethylamino) propylamine in 500 mL water. This was shaken then extracted once with 300 mL chloroform and once with 200 mL chloroform. The combined organics were washed 4 times with 200 mL 1N HCI then once with 200 mL brine. The organics were dried with MgS04, treated with charcoal then filtered and the solvents removed in vacuo. The residue was triturated with 100 mL methanol, filtered, and rinsed twice with 25 mL methanol. The solid was dried under vacuum to yield the pyrrolyl acetate (13.58 g, 48.1 mmol) as a tan powder.
		A. 4-Cyanobenzoyl chloride (14.61 g, 88.2 mmol) was suspended in 75 mL in a 3-neck flask. Methyl-N-methyl-2-pyrroleacetate (11.0 mL, 76.4 mmol) was added to the reaction. The flask was equipped with a reflux condenser and a nitrogen bubbler. Nitrogen was gently bubbled through the reaction as it was heated at 105 C. for 22.5 hours. The reaction was then diluted with 50 mL toluene and poured into a solution of 50 mL 3-(diethylamino)propylamine in 500 mL water. This was shaken then extracted once with 300 mL chloroform and once with 200 mL chloroform. The combined organics were washed 4 times with 200 mL 1N HCl then once with 200 mL brine. The organics were dried with MgSO4, treated with charcoal then filtered and the solvents removed in vacuo. The residue was triturated with 100 mL methanol, filtered, and rinsed twice with 25 mL methanol. The solid was dried under vacuum to yield the pyrrolyl acetate (13.58 g, 48.1 mmol) as a tan powder.

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2003,vol. 13,p. 1341 - 1344
[2]Patent: WO2003/87090,2003,A2 .Location in patent: Page/Page column 82
[3]Patent: US2004/192720,2004,A1 .Location in patent: Page 35-36

30
[ 6068-72-0 ]
[ 27514-07-4 ]
[ 643026-80-6 ]

Reference： [1]Journal of the American Chemical Society,2003,vol. 125,p. 15191 - 15199

31
[ 6068-72-0 ]
[ 1117-97-1 ]
[ 116332-64-0 ]

Reference： [1]Organic Letters,2005,vol. 7,p. 1427 - 1429
[2]Bioorganic and Medicinal Chemistry Letters,2005,vol. 15,p. 4019 - 4022

32
[ 398495-65-3 ]
[ 6068-72-0 ]
3-(4-cyano-benzoylamino)-4,6-dihydro-pyrrolo[3,4-c]pyrazole-1,5-dicarboxylic acid 5-tert-butyl ester 1-ethyl ester [ No CAS ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2006,vol. 16,p. 1084 - 1090

33
[ 6068-72-0 ]
[ 98-80-6 ]
[ 1503-49-7 ]

Yield	Reaction Conditions	Operation in experiment
98%	With water monomer; anhydrous sodium carbonate; 3-butyl-1-methyl-1H-imidazol-3-ium hexafluorophosphate at 60℃; for 2h;
95%	With potassium carbonate In water monomer; acetone at 50℃; for 0.75h;
75%	With copper(I) thiophene-2-carboxylate; triphenylphosphine In diethyl ether at 20℃; for 1h;

75%	With copper(I) thiophene-2-carboxylate; triphenylphosphine; Palladium⁽⁰⁾ bis(dibenzylideneacetone) In diethyl ether at 20℃; for 1h; Schlenk technique; Inert atmosphere;	1 4.3. General procedure for synthesis of unsymmetrical ketones by the cross-coupling reaction of arylboronic acids with acid chlorides General procedure: 4.3.1 Benzophenone (3a) 18 To phenylboronic acid (1a, 244 mg, 2 mmol), CuTC (191 mg, 1 mmol), Pd(dba)2 (29 mg, 0.05 mmol), and PPh3 (26.2 mg, 0.1 mmol), were added dry Et2O (30 mL) and benzoyl chloride (2a, 116 μL, 1 mmol) at rt and the reaction was monitored by GC and TLC. After completion of the reaction, the reaction mixture was passed briefly through a Celite pad. Further, the pad was washed with Et2O (2*10 mL). The combined organics were concentrated with a rotary evaporator to give a viscous oil or solid. The residue was purified by flash column chromatography on silica gel (hexane/EtOAc=9:1, Rf=0.47), benzophenone (3a) (142 mg, 0.78 mmol, 78%) was obtained as a white solid.
60%	With tripotassium phosphate tribasic; palladium diacetate; tricyclohexylphosphine tetrafluorohydroborate for 0.166667h; Milling; Sealed tube; chemoselective reaction;
55%	With sodium lauryl sulfate; potassium carbonate In water monomer at 60℃; for 6h;
27%	With trans-(Et₃NH)₂[PdCl₂(Ph₂Pferrocene-1,1′-diylSO₃-κP)₂]; sodium salt of phosphorous acid at 50℃; for 3h; Inert atmosphere; Schlenk technique; Sealed tube;
17%	With C₄₂H₃₆ClFeN₂O₄PPdS*C₆H₁₅N; anhydrous sodium carbonate In water monomer; toluene at 50℃; for 1h; Inert atmosphere; Schlenk technique; Sealed tube;

Reference： [1]Xin, Bingwei; Zhang, Yuhong; Cheng, Kai [Journal of Organic Chemistry, 2006, vol. 71, # 15, p. 5725 - 5731]
[2]Movassagh, Barahman; Hajizadeh, Fatemeh; Mohammadi, Elmira [Applied Organometallic Chemistry, 2018, vol. 32, # 1]
[3]Nishihara, Yasushi; Inoue, Yoshiaki; Fujisawa, Mamoru; Takagi, Kentaro [Synlett, 2005, # 15, p. 2309 - 2312]
[4]Ogawa, Daisuke; Hyodo, Keita; Suetsugu, Masato; Li, Jing; Inoue, Yoshiaki; Fujisawa, Mamoru; Iwasaki, Masayuki; Takagi, Kentaro; Nishihara, Yasushi [Tetrahedron, 2013, vol. 69, # 12, p. 2565 - 2571]
[5]Zhang, Jin; Zhang, Pei; Ma, Yangmin; Szostak, Michal [Organic Letters, 2022, vol. 24, # 12, p. 2338 - 2343]
[6]Xin, Bingwei; Zhang, Yuhong; Cheng, Kai [Synthesis, 2007, # 13, p. 1970 - 1978]
[7]Zábranský, Martin; Císařová, Ivana; Štěpnička, Petr [Organometallics, 2018, vol. 37, # 10, p. 1615 - 1626]
[8]Škoch, Karel; Císařová, Ivana; Štěpnička, Petr [Organometallics, 2016, vol. 35, # 19, p. 3378 - 3387]

34
[ 6270-44-6 ]
[ 6068-72-0 ]
[ 905601-20-9 ]

Yield	Reaction Conditions	Operation in experiment
34%	With sodium 4-cyanobenzoate at 180 - 190℃; for 7h;

Reference： [1]Gobbi, Silvia; Cavalli, Andrea; Rampa, Angela; Belluti, Federica; Piazzi, Lorna; Paluszcak, Anja; Hartmann, Rolf W.; Recanatini, Maurizio; Bisi, Alessandra [Journal of Medicinal Chemistry, 2006, vol. 49, # 15, p. 4777 - 4780]

35
[ 89-54-3 ]
[ 6068-72-0 ]
[ 1001340-11-9 ]

Yield	Reaction Conditions	Operation in experiment
97%	In tetrahydrofuran; for 72h;	EXAMPLE 24. Synthesis of 2-Chioro-5-(4-Cvano-Benzoylaminot-Benzoic Acid(Intermediate 16)16[01601 5-Amino-2-chloro-benzoic acid (0.355 g, 2.06 mmol) was diluted with THF (12 mL), treated with 4-cyano-benzoyl chloride (0.377 g, 2.23 mmol) and stirred for 72h. Solvents were then removed and resulting solids were triturated with DCM. After filtration, the title compound was obtained as a white solid (0.6 g, 97percent).

Reference： [1]Patent: WO2008/8234,2008,A1 .Location in patent: Page/Page column 57

36
[ 39959-51-8 ]
[ 6068-72-0 ]
[ 929803-17-8 ]

Reference： [1]Angewandte Chemie - International Edition,2007,vol. 46,p. 576 - 579
[2]Chemistry - A European Journal,2008,vol. 14,p. 1238 - 1252

37
[ 6068-72-0 ]
[ 82104-74-3 ]

Reference： [1]Il Farmaco,2001,vol. 56,p. 715 - 718

38
[ 874-89-5 ]
[ 6068-72-0 ]

Reference： [1]Journal of the Chemical Society,1942,p. 103,107

39
[ 6068-72-0 ]
[ 874-89-5 ]

Reference： [1]Chemical and pharmaceutical bulletin,1976,vol. 24,p. 1059 - 1063

40
[ 769-92-6 ]
[ 6068-72-0 ]
[ 569332-73-6 ]

Yield	Reaction Conditions	Operation in experiment
91%	With pyridine In dichloromethane at 0 - 20℃; for 2.08333h;	3.1 Example 3; Preparation of N- (4-tert-butylphenyl) -4- (2- thiazolinyl)benzamide (If-I); (the 1st step); To a mixture of 4-tert-butyl aniline (compound 3: 1.64g, llmmole) , pyridine (1.03g, 13mmole) and dichloromethane (1OmL) was added a dichloromethane (1OmL) solution of 4-cyanobenzoyl chloride (compound 2b: 1.66g, lOmmole) under ice cooling over 5 minutes and stirred at rt for 2 hours. To the reaction mixture was added water (15OmL) and IM HCl (2OmL), and the product was extracted with ethyl acetate (20OmL) . The extract was washed with saturated brine, dried over MgSU4 and concentrated in vacuo. The resulting residue was recrystallized from ethyl acetate/n-hexane to give N- (4- tert-butylphenyl) -4-cyanobenzamide (compound 4b: 2.52g, yield 91%) as a colorless crystalline. Mp.210-2110C.
	With N-ethyl-N,N-diisopropylamine In tetrahydrofuran at 20℃;	4.A EXAMPLE 4A N-(4-tert-butylphenyl)-4-cyanobenzamide 4-cyanobenzoyl chloride (2 g, 12.08 mmol), DIEA (7.3 mL, 42 mmol), and 4-tert-butylaniline (1.9 mL, 11.9 mmol) were stirred in tetrahydrofuran (50 mL) overnight at room temperature. The tetrahydrofuran was removed under reduced pressure and replaced with ethyl acetate. The ethyl acetate was washed with H2O and brine, dried over Na2SO4, filtered, and the filtrate concentrated under reduced pressure. The residue was purified by column chromatography on silica gel (eluant gradient from 8:2 hexanes:ethyl acetate to 1:1 hexanes:ethyl acetate) to afford the title compound as a solid. 1H NMR (300 MHz, DMSO-d6) δ 10.41 (s, 1H), 8.08-8.12 (m, 2H), 8.01-8.04 (m, 2H), 7.66-7.69 (m, 2H), 7.37-7.41 (m, 2H), 1.28 (s, 9H); MS (ESI+) m/z 279 (M+H)+.

Reference： [1]Current Patent Assignee: SHIONOGI & CO., LTD. - WO2007/69773, 2007, A1 Location in patent: Page/Page column 67-68
[2]Current Patent Assignee: ABBVIE INC - US2005/85512, 2005, A1 Location in patent: Page/Page column 10

41
[ 141-86-6 ]
[ 6068-72-0 ]
[ 850083-78-2 ]

Yield	Reaction Conditions	Operation in experiment
47%	Stage #1: 2.6-diaminopyridine; 4-cyanobenzoyl chlorIde In 1,4-dioxane at 20℃; for 2h; Stage #2: With sodium hydroxide; water In 1,4-dioxane	66 Example 66. 4-Cyano-N- (6- (1-methylpiperidin-4-ylamino) pyridin-2-yl) benzamide hydrochloride; Combine 4-cyanobenzoyl chloride (300 J. L, 1.80 mmol), 2,6-diaminopyridine (600 mg, 5.5 mmol, and dioxane (10 mL) ; stir at room temperature for 2 hr. Pour into water and adjust to pH>12 by the addition of 5N NaOH. Extract with CH2Cl2 twice, combine organics, dry over MgS04, and concentrate. Chromatograph (silica gel, eluting with 0-10% methanol/CH2Cl2). Dissolve the purified intermediate N- (6-amino-pyridin- 2-yl) -4-cyano-benzamide (202 mg, 0.84 mmol, 47%) in THF (10 mL). Add to this 1- methyl-4-piperidone (77 mg, 0.68 mmol), acetic acid (150 L, 2.5 mmol), and sodium triacetoxyborohydride (440 mg, 2.10 mmol). Stir the reaction at room temperature for 18 hr, and quench by the addition of saturated aqueous NaHC03. Extract the aqueous layer with ethylacetate twice, wash the combined organics with saturated aqueous NaCl, dry over MgS04, and concentrate. Chromatograph the material (silica gel, eluting with 0- 20% 2M NH3 in methanol/CH2Cl2). Dissolve the clean material (10.4 mg, 5%) in methanol and add 1 equivalent (1.7 mg) of NH4Cl. Sonicate the reaction at room temperature for 15 min, then concentrate to provide the title compound: mass spectrum (ion spray) : m/z = 336.0 (M+1).

Reference： [1]Current Patent Assignee: ELI LILLY & CO - WO2005/35499, 2005, A1 Location in patent: Page/Page column 82

42
[ 646-24-2 ]
[ 6068-72-0 ]
[ 862252-23-1 ]

Yield	Reaction Conditions	Operation in experiment
81%	With triethylamine; In DMF (N,N-dimethyl-formamide); at 0 - 20℃;	To a cold solution (0 C.) of 1,9-diaminononane (296 mg, 1.9 mmol) and triethylamine (0.65 mL, 4.6 mmol) in DMF (8 mL) was added 4-cyanobenzoyl chloride (685 mg, 4.1 mmol). The mixture was stirred overnight at room temperature, and then diluted with water. The beige solid that precipitated was collected by filtration and dried in vacuo, giving the corresponding amide (0.64 g, 1.54 mmol, 81% yield).
81%	With triethylamine; In DMF (N,N-dimethyl-formamide); at 0 - 20℃;	Step 1: To a cold solution (0 C) of 1, 9-diaminononane (296 mg, 1.9 mmol) and triethylamine (0.65 mL, 4.6 mmol) in DMF (8 mL) was added 4-cyanobenzoyl chloride (685 mg, 4.1 mmol). The mixture was stirred overnight at room temperature, and then diluted with water. The beige solid that precipitated was collected by filtration and dried iii vacuo, giving the corresponding amide (0.64 g, 1.54 mmol, 81 % yield).

Reference： [1]Patent: US2005/182118,2005,A1 .Location in patent: Page/Page column 31
[2]Patent: WO2005/79780,2005,A1 .Location in patent: Page/Page column 65

43
[ 25945-96-4 ]
[ 6068-72-0 ]
C₂₁H₁₅N₃O₄ [ No CAS ]

Reference： [1]Journal of Medicinal Chemistry,2008,vol. 51,p. 1126 - 1135

44
[ 5464-79-9 ]
[ 6068-72-0 ]
[ 313662-36-1 ]

Reference： [1]European Journal of Medicinal Chemistry,2008,vol. 43,p. 1519 - 1524

45
[ 280773-17-3 ]
[ 6068-72-0 ]
[ 330942-01-3 ]

Yield	Reaction Conditions	Operation in experiment
91%	With pyridine In tetrahydrofuran at 20℃; for 2h; Autoclave; Industrial scale;	5 Preparation of a compound of formula D At a temperature of 20 ° C, tetrahydrofuran (32 L, 5 by volume) was added successively to a 100 L autoclave,The compound of formula A (6.4 Kg, leq) and pyridine (2.0 L, 1.05 eq) were stirred and homogenized.A solution of cyanobenzoyl chloride (compound of formula B, 4. OKg, 1.05 eq) in tetrahydrofuran (11 L) was added,Stir for 2 hours. A saturated aqueous solution of sodium carbonate (21 L) was added dropwise to the system, followed by stirring for half an hour,The filter cake was washed with water (14.2 L) and ethyl acetate (14.2 L) and dried to give the compound of formula D (8.45 kg,Yield 91%).
77%	With pyridine In tetrahydrofuran at 20 - 22℃; for 4.75h; Inert atmosphere;	1 Example 1 : Preparation of N-(5-chloropyridin-2-yl)-2-(4-cyanobenzamido)- 5-methoxybenzamide A flask was charged with 2-Amino-N-(5-Chloro pyridine-2-yl)-5-methoxy benzamide (100 g), THF (1 .5L), and pyridine (1 1 .63 mL) at room temperature. To this a solution of 4-cyano benzoyl chloride (65.58 g) in THF (400 mL) was slowly added over a period of 45 min under inert atmosphere. The mixture was stirred for 4 hours at 20-22°C followed by filtration of the solid. The solid was washed with THF (100 mL) and was slurried in ethanol (500 mL), followed by subsequent filtration and washing with ethanol (100 mL). The solid was dried under vacuum at 35°C for 2 hours and then water (500 mL) was added and the mixture was cooled to 0-5°C followed by pH adjustment to ~12 with 20% ammonia solution (79 mL) at the same temperature. The mixture was stirred at 25°C for 1 h followed by filtration of solid, washing with methanol (200 mL) and drying under vacuum at 55°C for 18 hours to afford the title compound in about 77% yield.
70%	With pyridine In dichloromethane at 20℃;

	In tetrahydrofuran at 20℃;
263 g	With triethylamine In tetrahydrofuran at 10 - 20℃;	1.3 (3) Preparation of N-(5-chloropyridin-2-yl)-2-(4-cyanobenzoylamino)-5-methoxybenzamide (Compound II) 200 g (0.72 mol, 1.0 eq) of the compound of formula IV and 109 g (1.08 mol, 1.5 eq) of triethylamine were dissolved in 2000 ml of tetrahydrofuran at 10-20 ° C. A solution of 130 g (0.79 mol, 1.1 eq) of p-cyanobenzoyl chloride (Compound III, commercially available) and 1000 ml of tetrahydrofuran was added dropwise thereto.The progress of the reaction was monitored by HPLC; after the reaction was completed, it was filtered.The filter cake was washed with an appropriate amount of ethanol and dried under reduced pressure to give Compound II 263 g. HPLC purity: 98.7%.

Reference： [1]Current Patent Assignee: SICHUAN KELUN PHARMACEUTICAL COMPANY LIMITED - CN106831553, 2017, A Location in patent: Paragraph 0245; 0247; 0248; 0249
[2]Current Patent Assignee: DR REDDY'S LABORATORIES LIMITED - WO2018/42320, 2018, A1 Location in patent: Page/Page column 12
[3]Current Patent Assignee: TAKEDA PHARMACEUTICAL COMPANY LIMITED - WO2008/57972, 2008, A1 Location in patent: Page/Page column 33-34
[4]Location in patent: scheme or table Zhang, Penglie; Huang, Wenrong; Wang, Lingyan; Bao, Liang; Jia, Zhaozhong J.; Bauer, Shawn M.; Goldman, Erick A.; Probst, Gary D.; Song, Yonghong; Su, Ting; Fan, Jingmei; Wu, Yanhong; Li, Wenhao; Woolfrey, John; Sinha, Uma; Wong, Paul W.; Edwards, Susan T.; Arfsten, Ann E.; Clizbe, Lane A.; Kanter, James; Pandey, Anjali; Park, Gary; Hutchaleelaha, Athiwat; Lambing, Joseph L.; Hollenbach, Stanley J.; Scarborough, Robert M.; Zhu, Bing-Yan [Bioorganic and Medicinal Chemistry Letters, 2009, vol. 19, # 8, p. 2179 - 2185]
[5]Current Patent Assignee: HAISCO PHARMACEUTICAL GROUP CO., LTD. - CN104693114, 2019, B Location in patent: Paragraph 0085; 0092-0095

46
[ 28557-00-8 ]
[ 6068-72-0 ]
[ 1503-49-7 ]

Yield	Reaction Conditions	Operation in experiment
91%	In 1-methyl-pyrrolidin-2-one at 25℃; for 0.5h;

Reference： [1]Xu, Hanhui; Ekoue-Kovi, Kekeli; Wolf, Christian [Journal of Organic Chemistry, 2008, vol. 73, # 19, p. 7638 - 7650]

47
[ 4221-99-2 ]
[ 6068-72-0 ]
[ 848030-37-5 ]

Yield	Reaction Conditions	Operation in experiment
71%	In pyridine at 20℃; for 2h;

Reference： [1]Matsumura, Kazuyuki; Mori, Tadashi; Inoue, Yoshihisa [Journal of the American Chemical Society, 2009, vol. 131, # 47, p. 17076 - 17077]

48
[ 17626-40-3 ]
[ 6068-72-0 ]
[ 38224-22-5 ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2009,vol. 19,p. 4059 - 4063

49
[ 22990-77-8 ]
[ 6068-72-0 ]
C₁₄H₁₇N₃O [ No CAS ]
C₁₄H₁₇N₃O [ No CAS ]

Reference： [1]Chirality,2010,vol. 22,p. 693 - 698

50
[ 6068-72-0 ]
[ 93339-98-1 ]
[ 1257513-85-1 ]

Reference： [1]Chemical and Pharmaceutical Bulletin,2010,vol. 58,p. 1107 - 1110

51
[ 141-86-6 ]
[ 6068-72-0 ]
[ 1310423-95-0 ]

Yield	Reaction Conditions	Operation in experiment
94%	With triethylamine In dichloromethane at 20℃; for 22h; Cooling with ice;
68%	With triethylamine In tetrahydrofuran; toluene for 2.5h; Reflux;	4.1.2. General procedure A: synthesis of cyano-substituted carboxamides General procedure: To a solution of carbonyl chloride (dry toluene or dry DMF) was added dropwise a solution of appropriate amine (dry THF or dry toluene) or a solution of 4-aminobenzonitrile (toluene), followed by the addition of Et3N. The mixture was refluxed for 1.5-14 h. After cooling, precipitated crystals were filtered off, washed with diluted HCl and water, and recrystallized.
5.4 g	With triethylamine In chloroform; acetonitrile Cooling;

Reference： [1]Watanabe, Hiroyuki; Tanaka, Kazuo; Chujo, Yoshiki [Journal of Organic Chemistry, 2019, vol. 84, # 5, p. 2768 - 2778]
[2]Location in patent: experimental part Jarak, Ivana; Marjanović, Marko; Piantanida, Ivo; Kralj, Marijeta; Karminski-Zamola, Grace [European Journal of Medicinal Chemistry, 2011, vol. 46, # 7, p. 2807 - 2815]
[3]Location in patent: experimental part Lee, Ji Ha; Lee, Hyejin; Seo, Sungmin; Jaworski, Justyn; Seo, Moo Lyong; Kang, Sunwoo; Lee, Jin Yong; Jung, Jong Hwa [New Journal of Chemistry, 2011, vol. 35, # 5, p. 1054 - 1059]

52
[ 1476-39-7 ]
[ 6068-72-0 ]
[ 500715-55-9 ]

Yield	Reaction Conditions	Operation in experiment
72%	With triethylamine; In dichloromethane; at 20℃; for 12h;	General procedure: A solution of an appropriate aliphatic diamine (10 mmol) in dichloromethane (30 mL) and triethylamine (2.8 mL) was added dropwise to a stirred, ice cooled solution of 4-cyanobenzoyl chloride (3.31 g, 20 mmol) in dichloromethane (30 mL). The reaction mixture was stirred at room temperature for 12 h (progress of the reaction was followed by TLC), then the solvent was evaporated under reduced pressure and the residue was washed with 1 M NaHCO3, 1 M HCl and water, then dried over anhydrous CaCl2. Analytical samples were obtained after recrystalisation from DMSO-water mixtures (50-90 % DMSO).

Reference： [1]European Journal of Medicinal Chemistry,2012,vol. 48,p. 164 - 173

53
[ 1476-39-7 ]
[ 6068-72-0 ]
N,N'-pentane-1,5-diylbis(4-amidinobenzamide) dihydrochloride [ No CAS ]

Reference： [1]European Journal of Medicinal Chemistry,2012,vol. 48,p. 164 - 173

54
[ 6068-72-0 ]
[ 65-45-2 ]
[ 1262725-52-9 ]

Yield	Reaction Conditions	Operation in experiment
94%	With 1,8-diazabicyclo[5.4.0]undec-7-ene In acetonitrile at 20℃; for 24h;	p2 Acetonitrile (600 mL) and 355.2 g of DBU were added to 160.0 g of salicylamide and dissolved. To this solution, 193.2 g of 4-cyanobenzoyl chloride was added, and the mixture was stirred at room temperature for 24 hours. To the resulting reaction solution, 1,200 mL of water and 150 mL of hydrochloric acid were added, and the obtained solid was filtered and washed with water to obtain 292.8 g of Synthetic Intermediate pC (yield: 94%).
91%	With pyridine for 4h; Reflux; Inert atmosphere;

Reference： [1]Current Patent Assignee: FUJIFILM HOLDINGS CORP. - EP2460799, 2012, A1 Location in patent: Page/Page column 31-32
[2]Location in patent: experimental part Stec, Jozef; Huang, Qingqing; Pieroni, Marco; Kaiser, Marcel; Fomovska, Alina; Mui, Ernest; Witola, William H.; Bettis, Samuel; McLeod, Rima; Brun, Reto; Kozikowski, Alan P. [Journal of Medicinal Chemistry, 2012, vol. 55, # 7, p. 3088 - 3100]

55
[ 932738-80-2 ]
[ 6068-72-0 ]
[ 932738-61-9 ]

Reference： [1]Journal of Medicinal Chemistry,2012,vol. 55,p. 11042 - 11051

56
[ 932738-80-2 ]
[ 6068-72-0 ]
[ 1414953-55-1 ]

Reference： [1]Journal of Medicinal Chemistry,2012,vol. 55,p. 11042 - 11051

57
[ 6068-72-0 ]
[ 35776-95-5 ]

Reference： [1]European Journal of Organic Chemistry,2013,p. 4918 - 4932
[2]Journal of Organometallic Chemistry,2015,vol. 794,p. 136 - 145
[3]Tetrahedron Letters,2018,vol. 59,p. 2299 - 2301
[4]Advanced Synthesis and Catalysis,2019,vol. 361,p. 1777 - 1780

58
[ 6068-72-0 ]
[ 3016-97-5 ]

Reference： [1]European Journal of Organic Chemistry,2013,p. 4918 - 4932

59
[ 6068-72-0 ]
[ 1503-49-7 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 2 steps 1: triethylamine / dichloromethane / 2 h / 0 - 20 °C 2: tetrahydrofuran / 3 h / 0 - 20 °C / Inert atmosphere
	Multi-step reaction with 2 steps 1: dmap; triethylamine / dichloromethane / 2 h / 0 - 20 °C / Inert atmosphere; Schlenk technique 2: (bis(tricyclohexyl)phosphine)palladium(II) dichloride; potassium carbonate; tricyclohexylphosphine / 1,4-dioxane / 6 h / 110 °C / Inert atmosphere; Schlenk technique
	Multi-step reaction with 2 steps 1: dmap; triethylamine / dichloromethane / 2 h / 0 - 20 °C / Inert atmosphere; Schlenk technique 2: (bis(tricyclohexyl)phosphine)palladium(II) dichloride; tricyclohexylphosphine; potassium carbonate / 1,4-dioxane / 10 h / 110 °C / Inert atmosphere; Schlenk technique

	Multi-step reaction with 2 steps 1: dmap; triethylamine / dichloromethane / 0 - 20 °C / Inert atmosphere 2: boric acid; potassium carbonate; palladium diacetate; tricyclohexylphosphine tetrafluoroborate / tetrahydrofuran / 15 h / 65 °C / Inert atmosphere
	Multi-step reaction with 2 steps 1: triethylamine / N,N-dimethyl acetamide / 1 h / 0 °C 2: bis-triphenylphosphine-palladium(II) chloride; potassium phosphate / toluene / 4 h / 65 °C / Inert atmosphere
	Multi-step reaction with 2 steps 1: pyridine / 20 °C 2: allylchloro[1,3-bis(2,6-di-isopropylphenyl)imidazol-2-ylidine]palladium(II); potassium carbonate / 1,4-dioxane / 15 h / 110 °C / Sealed tube; Inert atmosphere
	Multi-step reaction with 2 steps 1: triethylamine; dmap / dichloromethane / 0 - 20 °C 2: palladium diacetate; potassium carbonate; tricyclohexylphosphine tetrafluoroborate / neat (no solvent) / 0.17 h / Milling

Reference： [1]Harikrishna, Kommidi; Rakshit, Ananya; Aidhen, Indrapal Singh [European Journal of Organic Chemistry, 2013, # 22, p. 4918 - 4932]
[2]Li, Xijing; Zou, Gang [Chemical Communications, 2015, vol. 51, # 24, p. 5089 - 5092]
[3]Li, Xijing; Zou, Gang [Journal of Organometallic Chemistry, 2015, vol. 794, p. 136 - 145]
[4]Meng, Guangrong; Szostak, Michal [Organic and Biomolecular Chemistry, 2016, vol. 14, # 24, p. 5690 - 5707]
[5]Wu, Hongxiang; Li, Yue; Cui, Ming; Jian, Junsheng; Zeng, Zhuo [Advanced Synthesis and Catalysis, 2016, vol. 358, # 23, p. 3876 - 3880]
[6]Luo, Zhongfeng; Liu, Tingting; Guo, Weijie; Wang, Zijia; Huang, Jingjun; Zhu, Yulin; Zeng, Zhuo [Organic Process Research and Development, 2018, vol. 22, # 9, p. 1188 - 1199]
[7]Ma, Yangmin; Shao, Lei; Szostak, Michal; Wang, Ruihong; Zhang, Jin; Zhang, Pei [Angewandte Chemie - International Edition, 2022, vol. 61, # 7][Angew. Chem., 2022, vol. 134, # 7]

60
[ 141-97-9 ]
[ 6068-72-0 ]
[ 49744-93-6 ]

Reference： [1]Heterocycles,2013,vol. 87,p. 1691 - 1698

61
[ 6068-72-0 ]
[ 52568-28-2 ]
[ 1620193-56-7 ]

Reference： [1]Organic Letters,2014,vol. 16,p. 3904 - 3907
[2]Chemistry - A European Journal,2015,vol. 21,p. 205 - 209

62
[ 6068-72-0 ]
[ 43038-36-4 ]

Reference： [1]Bulletin of the Korean Chemical Society,2014,vol. 35,p. 2271 - 2276
[2]Chemistry - A European Journal,2015,vol. 21,p. 9550 - 9555

63
[ 54468-86-9 ]
[ 6068-72-0 ]
C₁₆H₁₅N₃O₃S [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
70%	With triethylamine; In dichloromethane; at 29℃; for 2h;	4-Cyanobenzoyl chloride (1.0 eq) was added to a solution of <strong>[54468-86-9]2-amino-N,N-dimethylbenzenesulfonamide</strong> (1.0 eq) and TEA (1.5 eq) in DCM. The reaction mixture was stirred at 29 C. for about 2 h. TLC indicated starting material had disappeared. The reaction mixture was quenched with sat'd. aq. NaHCO3, extracted with DCM, dried over anhydrous Na2SO4 and concentrated. The residue was purified by prep-HPLC to afford compound 56 (yield: 70%). LCMS: Found 330.1 [M+H].

Reference： [1]Patent: US2014/271955,2014,A1 .Location in patent: Paragraph 0756

64
[ 35613-44-6 ]
[ 6068-72-0 ]
C₁₇H₁₄N₂O₃ [ No CAS ]

Reference： [1]RSC Advances,2014,vol. 4,p. 44629 - 44633

65
[ 6068-72-0 ]
[ 40004-08-8 ]
[ 1554476-63-9 ]

Yield	Reaction Conditions	Operation in experiment
65.4%	With triethylamine In tetrahydrofuran at 0 - 20℃; Inert atmosphere;

Reference： [1]Roth, Howard S.; Botham, Rachel C.; Schmid, Steven C.; Fan, Timothy M.; Dirikolu, Levent; Hergenrother, Paul J. [Journal of Medicinal Chemistry, 2015, vol. 58, # 9, p. 4046 - 4065]

66
[ 1446-61-3 ]
[ 6068-72-0 ]
C₂₈H₃₄N₂O [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
95%	With triethylamine; In dichloromethane; at 0 - 23℃;	To a solution of <strong>[1446-61-3](+)-dehydroabietylamine</strong>(1.0mmol) and triethylamine (3.0 mmol) in CH2Cl2 (5 mL), a solution of the corresponding acyl chloride (1.10 mmol) in CH2Cl2 (5 mL) was slowly added dropwise via syringe at 0 C. Theresulting reaction mixture was allowed to be warmed and was stirred at 23 C for 1-12 hr based on the reaction?s progress (TLC, MS) before it was quenche dwith an aqueous NH4Cl solution (10 mL). The organic phase was separated and the aqueous phase was extracted with CH2Cl2 (5mL x 3). The combined organic phase was dried over MgSO4 and concentrated under reduced pressure. The resulting crude product was purified via flash columnchromatography (SiO2; isocratic eluent: 20% EtOAc in petroleum ether) to provide the amide product.

Reference： [1]European Journal of Medicinal Chemistry,2015,vol. 102,p. 9 - 13

67
[ 1072-97-5 ]
[ 4998-07-6 ]
[ 6068-72-0 ]
[ 330941-99-6 ]

Yield	Reaction Conditions	Operation in experiment
70%	Stage #1: 5-bromo-2-pyridylamine; 4,5-dimethoxy-2-nitro-benzoic acid With pyridine; trichlorophosphate In pyridine at 0 - 20℃; for 0.5h; Stage #2: With tin(II) chloride dihdyrate In ethyl acetate for 1h; Reflux; Stage #3: 4-cyanobenzoyl chlorIde With pyridine In dichloromethane	199 N-{2-[N-(5-bromo(2-pyridyl))carbamoyl]-4,5-dimethoxyphenyl}(4-cyanophenyl)carboxamide To a solution of 4,5-dimethoxy-2-nitrobenzoic acid (2.2 gm, 10 mmol) and 2-amino-5-bromopyridine (2.4 gm, 14 mmol) in anhydrous pyridine (50 mL) at 0° C. was added POCl3 (1.9 mL, 20 mmol). After stirring at room temperature for 30 min, the reaction was complete. The mixture was concentrated and diluted with EtOAc (200 mL). The organic solution was washed with brine, dried and evaporated to give intermediate compound 1 (3.0 gm, 80%). MS found for C1-4H12BrN3O5 (M+H)+: 382.00, 383.95. (0742) A mixture of intermediate compound 1 (320 mg, 0.83 mmol) and SnCl2.2H2O (900 mg, 4.0 mmol) in EtOAc (10 mL) was refluxed for 1 hour. Reduction completed. The solid was filtered through a celite bed. The filtrate was diluted with EtOAc (50 mL), and the red solution was washed with 1N aq. NaOH solution (×3) and brine, dried and evaporated to give intermediate compound 2 (230 mg, 78%). MS found for C14H14BrN3O3 (M+H)+: 352.00, 354.05. (0743) To a solution of intermediate compound 2 (200 mg, 0.57 mmol) in a mixture of pyridine (3 mL) and DCM (10 mL) was added 4-cyanobenzoyl chloride (140 mg, 0.85 mmol). Precipitate formed immediately and the reaction was complete. The solid was collected by filtration and washed with DCM. After drying in vacco, the titled compound was obtained as a yellow solid in 70% yield (190 mg). MS found for C22H17BrN4O4 (M+H)+: 481.00, 483.00.

Reference： [1]Current Patent Assignee: TAKEDA PHARMACEUTICAL COMPANY LIMITED - US9108922, 2015, B2 Location in patent: Page/Page column 318

68
[ 6068-72-0 ]
[ 330942-05-7 ]

Reference： [1]Journal of Chemical Research,2015,vol. 39,p. 524 - 526
[2]Patent: CN107382897,2017,A
[3]Patent: WO2018/42320,2018,A1

69
[ 6068-72-0 ]
[ 330942-01-3 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 3 steps 1.1: triethylamine / tetrahydrofuran / 1.33 h / -5 - 20 °C 2.1: thionyl chloride; N,N-dimethyl-formamide / tetrahydrofuran / 3 h / 66 °C 3.1: sodium hydride / acetonitrile / 0.33 h / -5 - 0 °C 3.2: 1 h / -5 - 20 °C
	Multi-step reaction with 2 steps 1: triethylamine / dichloromethane; toluene / 8 h / 0 - 30 °C 2: 1,8-diazabicyclo[5.4.0]undec-7-ene / dichloromethane / 5 h / 0 - 40 °C

Reference： [1]Li, Jianye; Chen, Ligong; Yan, Xilong; Li, Yang; Wei, Daiyan; Wang, Donghua [Journal of Chemical Research, 2015, vol. 39, # 9, p. 524 - 526]
[2]Current Patent Assignee: ZHEJIANG HONGYUAN PHARMA - CN107382897, 2017, A

70
[ 6068-72-0 ]
[ 6705-03-9 ]
2-(4-cyanobenzamido)-5-methoxybenzoic acid [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
94%	With triethylamine In tetrahydrofuran at -5 - 20℃; for 1.33333h;	2-(4-Cyanobenzamido)-5-methoxybenzoic acid (7) 2-Amino-5-methoxybenzoic acid (4) (27.73 g, 165.88 mmol) was dissolved in THF (550 mL). The solution was stirred at -5-0 °C for 20 min and Et3N(17.92 g, 177.09 mmol ) was added to the solution. Then, 4-cyanobenzoylchloride (27.46 g, 165.88 mmol) in THF (50 mL) was added dropwiseto the above mixture at -5-0 °C. Subsequently, the mixture was stirredat room temperature for 1 h (monitored by TLC). Then the mixture wasevaporated to yield a white solid; yield 94% (46.13 g); m.p. 222.5-223.5°C; 1H NMR (600 MHz, DMSO-d6): δ 11.85 (s, 1 H), 8.46 (d, J = 6.0 Hz,1 H), 8.06 (s, 4 H), 7.49 (s, 1 H), 7.27 (s, 1 H), 3.79 (s, 3 H). 13C NMR (151MHz, DMSO-d6): δ 169.3, 162.8, 154.8, 138.6, 133.5, 132.9, 127.8, 122.4,120.0, 119.2, 118.2, 114.9, 114.1, 55.4. IR (KBr, νmax/cm-1): 3141, 2230,1705, 1666, 1612, 1539, 1508, 1387, 1315, 1203, 1037, 853, 822, 790, 732. HR-MS (ESI) m/z: [M+Na]+ calcd for C16H12N2O4+Na+ 319.0711; found319.0689.

Reference： [1]Li, Jianye; Chen, Ligong; Yan, Xilong; Li, Yang; Wei, Daiyan; Wang, Donghua [Journal of Chemical Research, 2015, vol. 39, # 9, p. 524 - 526]

71
[ 6068-72-0 ]
[ 50709-36-9 ]
4-cyano-N'-(2,6-dichlorophenyl)benzohydrazide [ No CAS ]

Reference： [1]Journal of Medicinal Chemistry,2016,vol. 59,p. 2139 - 2150

72
[ 368-47-8 ]
[ 6068-72-0 ]
[ 1503-49-7 ]

Yield	Reaction Conditions	Operation in experiment
35%	With tri-tert-butyl phosphine; palladium diacetate; cesium fluoride In 5,5-dimethyl-1,3-cyclohexadiene at 140℃; for 24h; Inert atmosphere; Sealed tube;	General Procedure for the Palladium-Catalyzed Coupling of Acyl Chlorides with ArSiF3 General procedure: To a screw-capped vial in a glovebox, Pd(OAc)2 (0.020 mmol, 4.5 mg), PtBu3 (0.0800 mmol, 16.2 mg), CsF (1.400 mmol, 212.7 mg), and xylene (0.4 mL) were added in that order. The vial was then sealed and removed from the glovebox, an acyl chloride (0.4 mmol) and an aryltrifluorosilane (1.2 mmol) were successively added to the vial. The mixture was heated at 140 °C for 24 h. After the reaction, the resultant mixture was filtered through a pad of silica gel (2 g, eluent; EtOAc). After removal of the volatile materials by rotary evaporation, the filtrate was analyzed by GC (n-decane as a internal standard) or NMR (1,1,2,2-tetrachloroethane as a internal standard). The crude material was purified by silica gel column chromatography (eluent; hexane:EtOAc = 99:1).

Reference： [1]Ogiwara, Yohei; Maegawa, Yuki; Sakino, Daisuke; Sakai, Norio [Chemistry Letters, 2016, vol. 45, # 7, p. 790 - 792]

73
[ 698-70-4 ]
[ 6068-72-0 ]
[ 60-34-4 ]
[ 4301-14-8 ]
4-(5-(4-(dimethylamino)phenyl)-1-methyl-1H-pyrazol-3-yl)benzonitrile [ No CAS ]

Reference： [1]Journal of Organic Chemistry,2016,vol. 81,p. 10328 - 10338

74
[ 6068-72-0 ]
[ 446065-11-8 ]
4-(cyclohexanecarbonyl)benzonitrile [ No CAS ]

Reference： [1]Journal of Organic Chemistry,2017,vol. 82,p. 1856 - 1863

75
[ 77385-90-1 ]
[ 6068-72-0 ]
ethyl 3-(4-cyanophenyl)-2-(dibenzylamino)-3-oxopropanoate [ No CAS ]

Reference： [1]Organic Letters,2017,vol. 19,p. 4339 - 4342

76
[ 6068-72-0 ]
[ 3958-47-2 ]
[ 1503-49-7 ]

Yield	Reaction Conditions	Operation in experiment
93%	With mesoporous MCM-41-immobilized phosphine-free heterogeneous palladium⁽⁰⁾-schiff base complex In tetrahydrofuran at 68℃; for 2h; Inert atmosphere; Green chemistry;

Reference： [1]Miao, Jiankang; Huang, Bin; Liu, Haiyi; Cai, Mingzhong [RSC Advances, 2017, vol. 7, # 67, p. 42570 - 42578]

77
[ 6068-72-0 ]
[ 1682-20-8 ]
4-cyano-N-(2,3,6-trifluoropyridin-4-yl)benzamide [ No CAS ]

Reference： [1]Journal of the American Chemical Society,2017,vol. 139,p. 13092 - 13101

78
[ 6068-72-0 ]
[ 1682-20-8 ]
4-cyano-N-(perfluoropyridin-4-yl)benzamide [ No CAS ]

Reference： [1]Journal of the American Chemical Society,2017,vol. 139,p. 13092 - 13101

79
[ 6068-72-0 ]
[ 6705-03-9 ]
2-(4-cyanophenyl)-6-methoxybenzo[d]-1,3-oxazin-4-one [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
88.6%	With triethylamine In dichloromethane; toluene at 0 - 30℃; for 8h;	1 Example 1:2- (4-Cyanophenyl) -6-Methoxybenzo [d] -1,3-oxazin-4-one(I)Preparation To a 150 mL reaction flask was added 5.0 g Methoxy-2-aminobenzoic acid (29.9 mmol) and 25 mL of dichloromethane,After stirring and dissolving, 5.0 mL of triethylamine (TEA) (36.1 mmol) was added.The mixture was cooled to 0-10 ° C and 5.9 g was added dropwise to the mixtureA solution of 4-cyanobenzoyl chloride (35.6 mmol) in toluene (25 mL)The reaction was warmed to room temperature and stirred for 8 hours. TLC detectionAfter the reaction of 5-methoxy-2-aminobenzoic acid,35mL of purified water was added to wash the reaction. Separate the organic layer,Heat to toluene reflux temperature for 2 hours. After TLC detection reaction is complete,The reaction solution was slowly cooled to 0-10 ° C, the precipitated solid was filtered, washed,7.36g of compound I was dried to give a yield of 88.6% and a purity of 99.8%.

Reference： [1]Current Patent Assignee: ZHEJIANG HONGYUAN PHARMA - CN107382897, 2017, A Location in patent: Paragraph 0072; 0073; 0074; 0087; 0088; 0089

80
[ 6068-72-0 ]
[ 77992-44-0 ]
C₁₃H₉BrN₄O [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
67%	With triethylamine; In dichloromethane; at 20℃; for 12h;	At room temperature, a mixture of 2-hydrazino-5-bromopyridine (1.0g, 5.3mmol), 4-cyanobenzoyl chloride (0.97g, 5.85mmol), triethyl amine (0.64g, 0.88mmol) and DCM (15mL) was stirred for 12hrs, and filtered. The solid was washed with DCM (5mL), dried under vacuum to give yellow solid 28-c (1.13g, yield 67percent). The produce was used directly for the next step without further purification. LC-MS (ESI): m/z = 319 [M+H]+.

Reference： [1]Patent: EP3275867,2018,A1 .Location in patent: Paragraph 0230; 0231

81
[ 6068-72-0 ]
[ 100-58-3 ]
[ 1503-49-7 ]

Yield	Reaction Conditions	Operation in experiment
43%	In 2-methyltetrahydrofuran at 25℃; for 1h;	General procedure: Compound 3 (6 mmol, 1.0 eq) in 2-methyltetrahydrofuran (15 mL) and phenyl magnesium bromide (9 mmol,1.5 eq) of 2-methyltetrahydrofuran solution (15 mL) passed through material channels A and B, respectively, via metering pumps P1, P2.Mixing into a mixing module M having a preset temperature of 25 ° C at a flow rate of 1 mL/min,After staying in the reaction module L for 1 h,The reaction solution flows out from the outlet D.The reaction liquid flowing out from the outlet D was collected in a 1 mol/L hydrochloric acid solution.Quenched by stirring,Saturated saline solution,Dry over anhydrous sodium sulfate,concentrate,Post-treatment by column chromatography, etc.Compound 4 was obtained.
43%	In 2-methyltetrahydrofuran at 25℃; for 1h; Flow reactor; Green chemistry;

Reference： [1]Current Patent Assignee: JIANGNAN UNIVERSITY - CN108409516, 2018, A Location in patent: Paragraph 0041-0044; 0046
[2]Zhang, Chuan-Tao; Zhu, Rui; Wang, Zheng; Ma, Bing; Zajac, Adrian; Smiglak, Marcin; Xia, Chun-Nian; Castle, Steven L.; Wang, Wen-Long [RSC Advances, 2019, vol. 9, # 4, p. 2199 - 2204]

82
[ 6068-72-0 ]
[ 116332-64-0 ]

Reference： [1]Organic Letters,2018,vol. 20,p. 5098 - 5102

83
[ 4414-89-5 ]
[ 6068-72-0 ]
1-(4-cyanobenzoyl)-1H-pyrrolo[2,3-b]pyridine-3-carbonitrile [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
39%	With triethylamine; In dichloromethane; at 0 - 20℃; for 4h;	General procedure: To a cooled (0 C) suspension of 1a-h20-26 (0.56 mmol) in anhydrousCH2Cl2 (2 mL), 0.72 mmol Et3N and 1.67 mmol of the appropriatechloride were added. The mixture was stirred at 0 C for 2 h and then atroom temperature for an additional 2 h. The solvent was evaporated,cold water was added, and the mixture was neutralized with 0.5 NNaOH. The reaction mixture was extracted with CH2Cl2 (3×15 mL),the solvent was dried over sodium sulfate, evaporated in vacuo, and thefinal compounds were purified by crystallization from ethanol (2a-i,3a,b,e, and 4b) or by column chromatography using cyclohexane/ethylacetate in different ratios: 1:1 (3d), 2:1 (3c and 4a), 3:1 (2l, 4b, 5a and5e), 5:1 (5c), or 6:1 (5b and 5d) as eluents

Reference： [1]Bioorganic and Medicinal Chemistry,2018,vol. 26,p. 5583 - 5595

84
[ 6068-72-0 ]
[ 599-04-2 ]
(R)-4-cyanobenzoic acid 4,4-dimethyl-2-oxo-tetrahydrofuran-3-yl ester [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
88.03%	With dmap; triethylamine In dichloromethane at 0 - 5℃;	4.2. General procedure for the synthesis of compounds 3a-3s General procedure: A solution of dry dichloromethane (10.0 mL) containing the substituted acyl chloride 2 (12.0 mmol) was added dropwise to the solution of dichloromethane (20.0 mL) containing D-(-)-pantolactone (1, 10.0 mmol, 1.30 g), 4-dimethylaminopyridine (1.0 mmol, 0.12 g) and triethylamine (12.0 mmol, 0.95 g). The reaction mixture was stirred overnight at 0-5 °C, and the reaction process was monitored by TLC. After completion of the reaction, the solvent was then removed under reduced pressure to give a residue which was extracted with ethyl acetate (3×50 mL). The solution was dried over anhydrous MgSO4 and concentrated under vacuum to obtain a slurry residue, which was purified by silica gel column chromatography (petroleum ether/ethyl acetate 2:1) to give products 3a-3s in yields of 57.19-94.94% (Scheme 1).

Reference： [1]Fang, Hua; He, Jianlin; Ran, Tan; Chen, Hui; Jin, Wenhui; Tang, Bowen; Hong, Zhuan; Fang, Meijuan [Bioorganic and Medicinal Chemistry, 2019, vol. 27, # 20]

85
[ 5396-38-3 ]
[ 6068-72-0 ]
[ 94004-39-4 ]

Yield	Reaction Conditions	Operation in experiment
84%	With aluminum (III) chloride In dichloromethane at 0 - 20℃; for 10h;	1 Preparation Example 1 Preparation of Compound of Formula 2 100 mL of methylene chloride was added to the reactor as a solvent,After dissolving aluminum chloride (4.67g. 3.5mol), it was cooled to 0 .In the state, 4-tertbutylanisole (164 g, 1.0 mol) and 4-cyanobenzoyl chloride (248 g, 1.5 mol) were added.After adding, mix and raise to room temperature, then react for 10 hours247 g of an intermediate compound (yield: 84%) was obtained.

Reference： [1]Current Patent Assignee: Dongwoo Fine-Chem (in: Sumitomo Chemical); SUMITOMO CHEMICAL COMPANY LIMITED - KR2020/24023, 2020, A Location in patent: Paragraph 0208; 0209

86
[ 46460-73-5 ]
[ 6068-72-0 ]
C₁₉H₁₉N₃O₃ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With N-ethyl-N,N-diisopropylamine In dichloromethane at 0℃;

Reference： [1]Abdel-Maksoud, Mohammed S.; Ali, Eslam M. H.; Ammar, Usama M.; Mersal, Karim I.; Oh, Chang-Hyun; Yoo, Kyung Ho [Bioorganic and medicinal chemistry, 2020, vol. 28, # 11]

87
[ 1593-60-8 ]
[ 6068-72-0 ]
N-((4-cyanobenzoyl)oxy)-4-methylbenzenesulfonamide [ No CAS ]

Reference： [1]Journal of the American Chemical Society,2020,vol. 142,p. 6698 - 6707

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. :	6068-72-0	MDL No. :	MFCD00001822
Formula :	C₈H₄ClNO	Boiling Point :	-
Linear Structure Formula :	-	InChI Key :	USEDMAWWQDFMFY-UHFFFAOYSA-N
M.W :	165.58	Pubchem ID :	80172
Synonyms :

Num. heavy atoms :	11
Num. arom. heavy atoms :	6
Fraction Csp3 :	0.0
Num. rotatable bonds :	1
Num. H-bond acceptors :	2.0
Num. H-bond donors :	0.0
Molar Refractivity :	41.34
TPSA :	40.86 Å²

GI absorption :	High
BBB permeant :	Yes
P-gp substrate :	No
CYP1A2 inhibitor :	Yes
CYP2C19 inhibitor :	No
CYP2C9 inhibitor :	No
CYP2D6 inhibitor :	No
CYP3A4 inhibitor :	No
Log Kp (skin permeation) :	-5.51 cm/s

[ CAS No. 6068-72-0 ] {[proInfo.proName]}

Quality Control of [ 6068-72-0 ]

Related Doc. of [ 6068-72-0 ]

Product Details of [ 6068-72-0 ]

Calculated chemistry of [ 6068-72-0 ]

Physicochemical Properties

Pharmacokinetics

Lipophilicity

Druglikeness

Water Solubility

Medicinal Chemistry

Safety of [ 6068-72-0 ]

Application In Synthesis of [ 6068-72-0 ]

[ 6068-72-0 ] Synthesis Path-Upstream 1~19

[ 6068-72-0 ] Synthesis Path-Downstream 1~87

Related Functional Groups of
[ 6068-72-0 ]

Aryls

Chlorides

Acyl Chlorides

Nitriles

Precautionary Statements-General

Prevention

Response

Storage

Disposal

Physical hazards

Health hazards

Environmental hazards

Inquiry

Log Po/w (iLOGP) :	1.63
Log Po/w (XLOGP3) :	2.54
Log Po/w (WLOGP) :	1.94
Log Po/w (MLOGP) :	1.35
Log Po/w (SILICOS-IT) :	2.3
Consensus Log Po/w :	1.95

Lipinski :	0.0
Ghose :	None
Veber :	0.0
Egan :	0.0
Muegge :	1.0
Bioavailability Score :	0.55

Log S (ESOL) :	-2.8
Solubility :	0.26 mg/ml ; 0.00157 mol/l
Class :	Soluble
Log S (Ali) :	-3.05
Solubility :	0.149 mg/ml ; 0.000902 mol/l
Class :	Soluble
Log S (SILICOS-IT) :	-3.04
Solubility :	0.151 mg/ml ; 0.000912 mol/l
Class :	Soluble

PAINS :	0.0 alert
Brenk :	1.0 alert
Leadlikeness :	1.0
Synthetic accessibility :	1.46

Signal Word:	Danger	Class:	8
Precautionary Statements:	P260-P261-P264-P270-P271-P280-P301+P312-P301+P330+P331-P302+P352-P303+P361+P353-P304+P340-P305+P351+P338-P310-P312-P321-P322-P330-P363-P405-P501	UN#:	3261
Hazard Statements:	H302-H312-H314-H332	Packing Group:	Ⅱ
GHS Pictogram:

Yield	Reaction Conditions	Operation in experiment
98%	for 1.5 h; Reflux	4-Cyanobenzoic acid (5) (30.00 g,203.90 mmol) was added to thionyl chloride (29.11 g, 244.68 mmol) in batches with magnetic stirring. Then, three drops of DMF were added to the solution. The reaction mixture was heated to reflux and stirred for 1.5 h (monitored by TLC). The solution was distilled at 235 °C to yield a white solid; yield 98percent (5.50 g); m.p. 67.2–68.2 °C; 1H NMR (600 MHz,DMSO-d6): δ 8.06 (d, J = 7.8 Hz, 2 H), 7.96 (d, J = 7.8 Hz, 2 H). 13C NMR(151 MHz, DMSO-d6): δ 165.9, 134.7, 132.6, 129.9, 118.1, 115.1. IR (KBr,νmax/cm–1): 3101, 3051, 2229, 1772, 1739, 1597, 1401, 1287, 1211, 1167,896, 851, 634. HR-MS (ESI) m/z: [M+H]+ calcd for C8H4ClNO+H+166.0053; found 166.0054.
93.3%	With oxalyl dichloride In dichloromethane at 0 - 25℃; for 3 h;	4-Cyanobenzoic acid (2.0 g, 13.6 mmol) was dissolved in dichloromethane (20 mL) at 0 ° C and oxalyl chloride (3.58, 27.611111101) was slowly added dropwise with the addition dropwise to 25 ° C : For 3 hours and concentrated to give the product (2.18, 93.3percent yield)

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Response
Code	Phrase
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P321
P322
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P361	Remove/Take off immediately all contaminated clothing.
P362	Take off contaminated clothing and wash before reuse.
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P373	DO NOT fight fire when fire reaches explosives.
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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.
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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.
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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.
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P401
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P411 + P235	Keep cool.
Disposal
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P501	Dispose of contents/container to ...
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