Month: March 2021

Electric Literature of 6136-93-2,Some common heterocyclic compound, 6136-93-2, name is 2,2-Diethoxyacetonitrile, molecular formula is C6H11NO2, traditional synthetic route has been very mature, but the traditional synthetic route has various shortcomings, such as complicated route, low yield, poor purity, etc, below Introduce a new synthetic route.

To a stirred solution of 2,2-diethoxyacetonitrile (XIX) (0.59 g, 4.57 mmol) in a vial containing MeOH (4.57 mL) was added MeONa (0.1 mL, 0.46 mmol) dropwise. The reaction was stirred at 35 C. for 20 h. HOAc was added (26.1 muL, 0.46 mmol) (checked that the pH is 7-8 using pH strips) followed by (4-bromo-3-chloro-phenyl)methanamine (XXII) (1.01 g, 4.57 mmol). The mixture was stirred at 35 C. for 40 h. The solvent was removed under vacuum. Sulfuric Acid (7.43 mL, 137.0 mmol) was then added and stirred at 35 C. for 16 h. NH4OH (60.6 mL, 141.6 mmol) was added at 0 C. The reaction was filtered through Celite and purified by C18 silica gel (240 g) [0?30% H2O/MeCN (0.1% Formic acid)] to produce a 1:1 mixture (by NMR) of 6-bromo-7-chloro-isoquinolin-3-amine (XXIII) and 6-bromo-5-chloroisoquinolin-3-amine (XXIV) (633.7 mg, 2.46 mmol, 53.9% yield). 1H NMR (499 MHz, DMSO-d6) delta ppm 6.23 (2H, s), 6.46 (2H, s), 6.57 (1H, s), 6.83 (1H, s), 7.40 (1H, d, J=8.51 Hz), 7.74 (1H, d, J=8.51 Hz), 8.05 (1H, s), 8.09 (1H, s), 8.81 (1H, s), 8.88 (1H, s); ESIMS found for C9H6BrClN2 m/z 256.9 (79BrM+H).

These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route 2,2-Diethoxyacetonitrile, its application will become more common.

Reference:
Patent; Samumed, LLC; KC, Sunil Kumar; Mak, Chi Ching; Eastman, Brian Walter; Cao, Jianguo; Mittapalli, Gopi Kumar; (82 pag.)US2019/125741; (2019); A1;,
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501-00-8, name is 2-(3-Fluorophenyl)acetonitrile, belongs to nitriles-buliding-blocks compound, is considered to be a conventional heterocyclic compound, which is widely used in drug synthesis. The chemical synthesis route is as follows. Product Details of 501-00-8

General procedure: General procedure for the reduction of nitrile by KBH4and CuCl2:To a 10 mL round-bottomed flask was added 2-(4-chlorophenyl)acetonitrile (0.1 5 g, 1 mmol), KBH4 (0.17 g, 3mmol), CuCl2 (0.03 g, 0.25 mmol) and 80 % isopropanol (1.6mL isopropanol and 0.4 mL water). The reaction completed in8 h at 60 C as evidenced by TLC (DCM:MeOH 10:1). Thereaction mixture was cooled to 25 C and removed the solvent.Ethyl acetate (5 mL) was added to the residue, washed withwater (1 mL) and brine (1 mL). The organic layer were dried withanhydrous Na2SO4, filtered and evaporated in vacuo to affordthe crude product.

The synthetic route of 501-00-8 has been constantly updated, and we look forward to future research findings.

Reference:
Article; Jiang, Han; Hu, Jialei; Xu, Xinliang; Zhou, Yifeng; Asian Journal of Chemistry; vol. 27; 10; (2015); p. 3564 – 3566;,
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Adding a certain compound to certain chemical reactions, such as: 92664-05-6, name is Potassium 1-cyano-3-ethoxy-2,3-dioxopropan-1-ide, belongs to nitriles-buliding-blocks compound, can increase the reaction rate and produce products with better performance than those obtained under traditional synthetic methods. Here is a downstream synthesis route of the compound 92664-05-6, SDS of cas: 92664-05-6

To a stirring suspension of crude 5-hydrazinylisoquinoline (prepared from Example 25 step a, 6.0 g, 37.7 mmol) and potassium 1-cyano-3-ethoxy-3-oxoprop-1-en-2-olate (8.1 g, 45.2 mmol) in ethanol (36 mL) was added a solution of 6 N aqueous hydrochloric acid (7.7 mL, 45.2 mmol) and deionized water (10 mL). The reaction mixture was heated at 90 C. for 5 h. After cooling to room temperature, the reaction mixture was concentrated in vacuo and the resulting residue was extracted with 2:1 chloroform/iPrOH. The organic layer was washed with aqueous saturated sodium bicarbonate and the organic layer was dried (Na2SO4), filtered, and concentrated in vacuo. The resulting solid was suspended in dichloromethane/diethyl ether and the yellow solid was collected by filtration to give the desired product (3.14 g, 11.1 mmol, 30%).

In the field of chemistry, the synthetic routes of compounds are constantly being developed and updated. I will also mention this compound in other articles, Potassium 1-cyano-3-ethoxy-2,3-dioxopropan-1-ide, other downstream synthetic routes, hurry up and to see.

Reference:
Patent; CHEMOCENTRYX, INC.; CHEN, Xi; FAN, Junfa; FAN, Pingchen; KRASINSKI, Antoni; LI, Lianfa; LUI, Rebecca M.; McMAHON, Jeffrey P.; POWERS, Jay P.; ZENG, Yibin; ZHANG, Penglie; US2013/225580; (2013); A1;,
Nitrile – Wikipedia,
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Synthetic Route of 72291-30-6,Some common heterocyclic compound, 72291-30-6, name is Methyl 2-cyano-2-methylpropanoate, molecular formula is C6H9NO2, traditional synthetic route has been very mature, but the traditional synthetic route has various shortcomings, such as complicated route, low yield, poor purity, etc, below Introduce a new synthetic route.

To a solution of 122-1 (2.0 g, 15.73 mmol, 1 eq), (Boc)20 (6.87 g, 31.46 mmol, 7.23 mL, 2 eq) and NiCl2 (203.9 mg, 1.57 mmol, 0.1 eq) in MeOH (40 mL) at 0C was added NaBH4 (4.17 g, 110.11 mmol, 7 eq) slowly portion-wise, and the resulting mixture was stirred at 20C for 16 h. The reaction mixture was quenched with NH4.H20 (10 mL), and then concentrated to remove solvent. And the residue was diluted with water (50 mL), and then extracted with EA (50 mL *3). The combined organic layers were washed with brine (50 mL), dried over anhydrous Na2S04, filtered and concentrated under reduced pressure to give a residue. The residue was purified by flash silica gel chromatography to give 122-2 (600 mg, 2.59 mmol, 16.5% yield). 1H NMR (400 MHz, CDCI3) d 4.97 (brs, 1H), 3.69 (s, 3H), 3.24 (d, J= 6.6 Hz, 2H), 1.44 (s, 9H), 1.19 (s, 6H).

These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route Methyl 2-cyano-2-methylpropanoate, its application will become more common.

Reference:
Patent; VIVACE THERAPEUTICS, INC.; KONRADI, Andrei W.; LIN, Tracy Tzu-Ling Tang; (559 pag.)WO2019/222431; (2019); A1;,
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These common heterocyclic compound, 5216-17-1, name is 2,3,5,6-Tetrafluorobenzonitrile, its traditional synthetic route has been very mature, but the traditional synthetic route has various shortcomings, such as complicated route, low yield, poor purity, etc, below Introduce a new synthetic route. Quality Control of 2,3,5,6-Tetrafluorobenzonitrile

[0154] NaH (60% in mineral oil, 128 mg, 3.2 mmol) was slowly added to a solution of 2,3-dihydroimidazo[1,2-cjquinazolin-9-ol (300 mg, 1.6 mmol) in THF (10 mL) at 0 C. The reaction mixture was degassed with N2 and stirred at 0 C for 30 mm. Then 2,3,5,6- tetrafluorobenzonitrile (308 mg, 1.8 mmol) was added and the mixture was stirred at room temperature for 18 hours. The reaction mixture was quenched by MeOH (5 mL) at 0 C. The resulting mixture was evaporated and the residue was purified on silica gel column flash chromatography (DCM/MeOH from 60:1 to 10:1, v/v) to afford 2-((2,3-dihydroimidazo[1,2- cjquinazolin-9-yl)oxy)-3,5,6-trifluorobenzonitrile (200 mg, 36% yield) as a yellow solid.

The synthetic route of 2,3,5,6-Tetrafluorobenzonitrile has been constantly updated, and we look forward to future research findings.

Reference:
Patent; ABM THERAPEUTICS, INC.; CHEN, Chen; (154 pag.)WO2019/60611; (2019); A1;,
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Related Products of 1558-81-2,Some common heterocyclic compound, 1558-81-2, name is Ethyl 1-Cyano-1-cyclopropanecarboxylate, molecular formula is C7H9NO2, traditional synthetic route has been very mature, but the traditional synthetic route has various shortcomings, such as complicated route, low yield, poor purity, etc, below Introduce a new synthetic route.

A) To a solution of 1-methyl-1H-pyrazol-3-amine (223 mg) in cyclopentyl methyl ether (5.0 mL) was added ethyl 1-cyanocyclopropanecarboxylate (0.90 ml). The reaction mixture was stirred at 120 C. for 30 hr, and diluted with ethyl acetate. The diluted solution was washed with water and saturated brine, and dried over anhydrous sodium sulfate, and the solvent was evaporated under reduced pressure. The residue was purified by silica gel column chromatography (ethyl acetate/hexane) to give the title compound (237 mg). MS (ESI+): [M+H]+190.8.

The synthetic route of 1558-81-2 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; Takeda Pharmaceutical Company Limited; Yoshida, Masato; TAKAMI, Kazuaki; TOMINARI, Yusuke; SHIOKAWA, Zenyu; SHIBUYA, Akito; SASAKI, Yusuke; GIBSON, Tony; TAKAGI, Terufumi; US2015/133451; (2015); A1;,
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Adding a certain compound to certain chemical reactions, such as: 127667-01-0, name is 2-Fluoro-5-methoxybenzonitrile, belongs to nitriles-buliding-blocks compound, can increase the reaction rate and produce products with better performance than those obtained under traditional synthetic methods. Here is a downstream synthesis route of the compound 127667-01-0, name: 2-Fluoro-5-methoxybenzonitrile

A mixture of 4-chloro-5-methyl-lH-pyrazole-3- carboxylic acid dibutylamide (1.5 g, 5.5 mmol), 2-fluoro-5-methoxybenzonitrile (1.1 g, 7.2 mmol), and cesium carbonate (1.8 g, 5.5 mmol) in dimethylformamide (5 mL) was microwaved at 130C for 30 minutes. The solvent was removed in vacuo. The crude material was eluted through a silica gel column with a 0 to 70% ethyl acetate / heptane gradient to afford the title compound (1.3 g, 59% yield) as a white solid. MS (ESI) [m/e, (M+H)+] = 403.5. NMR (400 MHz, chloroform-d) delta ppm 7.32 (d, J=8.5 Hz, 1 H), 7.18 – 7.22 (m, 1 H), 7.12 – 7.18 (m, 1 H), 3.84 (s, 3 H), 3.41 – 3.51 (m, 2 H), 3.32 – 3.41 (m, 2 H), 2.15 (s, 3 H), 1.54 – 1.66 (m, 2 H), 1.48 (qd, J=7.7, 7.5 Hz, 2 H), 1.26 – 1.40 (m, 2 H), 1.17 (ddd, J=14.9, 7.4, 7.3 Hz, 2 H), 0.89 (t, J=7.3 Hz, 3 H), 0.77 (t, J=7.3 Hz, 3 H).

If you are interested in these compounds, you can also browse my other articles.Thank you for taking the time to read this article. I hope you enjoyed it.

Reference:
Patent; NOVARTIS AG; VISSER, Michael Scott; YUSUFF, Naeem; WO2013/96049; (2013); A1;; ; Patent; NOVARTIS AG; FORD, Daniel; PORTER, John Robert; VISSER, Michael Scott; YUSUFF, Naeem; WO2013/96060; (2013); A1;,
Nitrile – Wikipedia,
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Synthetic Route of 630-18-2, These common heterocyclic compound, 630-18-2, name is Pivalonitrile, its traditional synthetic route has been very mature, but the traditional synthetic route has various shortcomings, such as complicated route, low yield, poor purity, etc, below Introduce a new synthetic route.

General procedure: To a solution of 4-bromobiphenyl 1a (3.0 mmol, 699.3 mg) in THF (3.0 mL) was added n-BuLi (4.5 mmol, 1.55 M in hexane, 2.87 mL) at 50 C. The obtained mixture was stirred for 30 min at 50 C under an argon atmosphere. Pivalonitrile (6.0 mmol, 498.8 mg) in THF (2.0 mL) was added to the mixture at 50 C and the obtained mixture was stirred for 30 min in the temperature range of 50 C to room temperature. MeOH (2.0 mL) was added to the mixture. Then, I2 (12.0 mmol, 3045.6 mg) and K2CO3 (12.0 mmol, 1658.4 mg) were added to the mixture at room temperature, and the obtained mixture was stirred for 6 h at 70 C. Sat. aq. Na2SO3 solution (20.0 mL) was added to the reaction mixture, and the product was extracted with AcOEt (10.0 mL x 3). The organic layer was dried over Na2SO4. After filtration and removal of the solvent, the residue was purified by silica-gel column chromatography (chloroform: n-hexane 1:1) to give 4-cyanobiphenyl 2a (451.6 mg, 84%).

The synthetic route of 630-18-2 has been constantly updated, and we look forward to future research findings.

Reference:
Article; Uchida, Ko; Togo, Hideo; Tetrahedron; vol. 75; 39; (2019);,
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Reference of 873697-68-8,Some common heterocyclic compound, 873697-68-8, name is 3-Amino-2-fluorobenzonitrile, molecular formula is C7H5FN2, traditional synthetic route has been very mature, but the traditional synthetic route has various shortcomings, such as complicated route, low yield, poor purity, etc, below Introduce a new synthetic route.

Example 28; 4-(3-(4-(Dimethylamino)benzamido)-2-fluoro henyl)-7-morpholino-9H- yrido[3,4-; 1. N-(3-Cyano-2-fluorophenyl)-4-(dimethylamino)benzamide; To a mixture of 3-amino-2-fluorobenzonitrile (2.24 g, 16.46 mmol) and 4- (dimethylamino)benzoyl chloride (3.46 g, 18.84 mmol) in 1,2-dichloroethane (50 mL) at rt was added pyridine (0.891 mL, 11.02 mmol). The resulting mixture was heated at 70 C for 5 hr. On cooling to room temperature, the mixture was diluted with ethyl acetate (250 mL), washed with water (5 x 60 mL) and brine (60 mL), and dried over anhydrous MgSO4. The organic solution was concentrated under vacuum, and the residue was subjected to ISCO (2 x 330 g silica gel, 25-50% ethyl acetate/hexane) to afford the desired product (4.11 g, 14.51 mmol, 88% yield) as a white solid.

These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route 3-Amino-2-fluorobenzonitrile, its application will become more common.

Reference:
Patent; BRISTOL-MYERS SQUIBB COMPANY; LIU, Chunjian; LIN, James; DELUCCA, George V.; BATT, Douglas G.; LIU, Qingjie; WO2011/159857; (2011); A1;,
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Researchers who often do experiments know that organic synthesis is a process of preparing more complex target molecules from simple raw materials through one or more chemical reactions. Generally, it requires fewer steps, and cheap raw materials. 6136-68-1, name is 3-Acetylbenzonitrile, A new synthetic method of this compound is introduced below., Application In Synthesis of 3-Acetylbenzonitrile

[00458] To a stirred solution of 3-acetylbenzonitrile (1 g, 6.89 mmol) in dry THF (30 mL) under inert atmosphere was added sodium hydride (60%>) (326 mg, 13.5 mmol) portion wise at 0C followed by dimethyl carbonate (1.24 g, 13.7 mmol). The reaction mixture was heated to 60 C and stirred for 7 h; progress of the reaction was monitored by TLC. The reaction mixture was quenched with dil. HC1 (2 mL), diluted with water (50 mL) and extracted with EtOAc (2 x 30 mL). The combined organic extracts were dried over anhydrous Na2SO4 and concentrated under reduced pressure to obtain the crude product. The crude material was purified by silica gel column chromatography eluting with 10% EtOAc/Hexane to afford compound H as a mixture of its enolic form (950 mg, 67.8%) as a pale yellow liquid. 1H NMR (500 MHz, DMSO-^): delta 8.40 (s, 1H), 8.31-8.22 (m, 1H), 8.19-8.12 (m, 1H), 7.77-7.75 (m, 1H), 4.29 (s, 2H), 3.64 (s, 3H). MS (ESI): m/z 204 [M+l] +.

The basis of chemical reaction formula synthesis, the synthesis route is composed of some specific reactions and combined according to certain logical thinking. We look forward to the emergence of more reaction modes in the future.

Reference:
Patent; SANFORD-BURNHAM MEDICAL RESEARCH INSTITUTE; COSFORD, Nicholas David, Peter; DHANYA, Raveendra, Panickar; SHEFFLER, Douglas, J.; WO2015/191630; (2015); A1;,
Nitrile – Wikipedia,
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