Month: December 2020

2941-29-9, name is Cyclopentanone-2-carbonitrile, 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. 2941-29-9

To a solution of intermediate 15-e ( 1.8 g, 6.01 mmol) in toluene (30.0 ml), was added 2-oxocyclopentanecarbonitrile (984 mg, 9.02 mmol) and 4- methylbenzenesulfonic acid hydrate ( 114 mg, 0.60 mmol) . The reaction was refluxed for 3 hours using a dean-stark and then cooled to room temperature. Saturated aqueous NaHC03 and ethyl acetate were added, the organic layer was separated, washed with brine, dried over MgS04, filtered and concentrated under reduced pressure. Purification by silica gel chromatography provided intermediate 15-f as beige solid . MS (m/z) M + H= 391.5

Statistics shows that 2941-29-9 is playing an increasingly important role. we look forward to future research findings about Cyclopentanone-2-carbonitrile.

Reference:
Patent; PHARMASCIENCE INC.; LAURENT, Alain; ROSE, Yannick; MORRIS, Stephen; JAQUITH, James; WO2012/135937; (2012); A1;,
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20249-16-5, Each compound has different characteristics, and only by selecting the characteristics of the compound suitable for a specific situation can the compound be applied on a large scale. 20249-16-5, name is 3-Oxocyclobutanecarbonitrile, This compound has unique chemical properties. The synthetic route is as follows.

3,3-difluorocyclobutanecarbonitrile[1268] Example 125 A (8.21 g, 86 mmol) in dichloromethane (135 mL) was stirred at room temperature, cooled to <10 C, added DAST (1 1.41 mL, 86 mmol), warmed to room temperature, and stirred for 2 hours. The mixture was poured into saturated aqeuous NaHCC (200 mL) and partitioned. The aqueous phase was extracted with 2 x 50 mL dichloromethane. The combined organic phase was dried (Na2S04), filtered, and concentrated to give Example 125B (9.14 g, 78 mmol, 90 % yield) as a brown oil. XH NMR (400 MHz, CDC13) ? 3.06 - 2.91 (m, 5H). 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; ABBVIE INC.; BAYBURT, Erol K.; CLAPHAM, Bruce; COX, Phil B.; DAANEN, Jerome F.; GOMTSYAN, Arthur; KORT, Michael E.; KYM, Philip R.; VOIGHT, Eric A.; SCHMIDT, Robert G.; DART, Michael J.; GFESSER, Gregory; WO2013/62964; (2013); A2;,
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A common compound: 64248-62-0, name is 3,4-Difluorobenzonitrile, belongs to nitriles-buliding-blocks compound, it can change the direction of chemical reaction, and react with certain compounds to generate new functional products. A new synthetic method of this compound is introduced below. 64248-62-0

A mixture of methyl (i?)-N-methyl-l-(7H-pyrrolo [2,3-Patent; HUTCHISON MEDIPHARMA LIMITED; SU, Wei-Guo; DENG, Wei; LI, Jinshui; JI, Jianguo; WO2012/22265; (2012); A1;,
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68119-31-3, Each compound has different characteristics, and only by selecting the characteristics of the compound suitable for a specific situation can the compound be applied on a large scale. 68119-31-3, name is 2-(2,2-Difluorobenzo[d][1,3]dioxol-5-yl)acetonitrile, This compound has unique chemical properties. The synthetic route is as follows.

A mixture of (2,2-difluoro-l,3-benzodioxol-5-yl)-acetonitrile (1.0 eq), 50 wt % aqueous KOH (5.0 eq) l-bromo-2-chloroethane (1.5 eq), and OCt4NBr (0.02 eq) is heated at 70 0C for 1 h. The reaction mixture is cooled then worked up with MTBE and water. The organic phase is washed with water and brine then the solvent is removed to afford (2,2-difluoro-l,3- benzodioxol-5-yl)-cyclopropanecarbonitrile.

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; VERTEX PHARMACEUTICALS INCORPORATED; WO2009/73757; (2009); A1;,
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52798-01-3, A common heterocyclic compound, 52798-01-3, name is Methyl (4-cyanophenyl)acetate, molecular formula is C10H9NO2, 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.

Methyl p-cyanophenylacetate (300 mg, 0.86 mmol), and tetrahydrofuran (2 mL) were added to a 25 mL singlemouth bottle, and stirred for 10 min under ice bath, then NaH (81 mg, 1.02 mmol, 60%) was added, and the reaction was continued under ice bath for 10 min. Then iodomethane (243 mg, 0.86 mmol) was added, and the reaction was continued for 1 hour while stirring, and after completion of the reaction, the reaction was quenched with water. The reaction mixture was adjusted to pH 3 with 2M hydrochloric acid solution, and extracted with ethyl acetate (10 mL33). The organic layers were combined, washed with saturated brine, dried over anhydrous sodium sulfate, and filtered, and then the filtrate was concentrated in vacuo to obtain a crude product. The crude product was passed through a column (ethyl acetate: petroleum ether = 1:1) to give the product (white oil, 190 mg), with a yield of 58.6%. 1H NMR (400 MHz, CDCl3) delta 7.62 (d, J= 8.3 Hz, 2H), 7.41 (d, J= 8.1 Hz, 2H), 3.78 (q, J= 7.1 Hz, 1H), 3.67 (s, 3H), 1.51 (d, J= 7.2 Hz, 3H). MS (ES) m/z: 190.0(MH+).

The synthetic route of 52798-01-3 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; Fudan University; WANG, Yonghui; HUANG, Yafei; YU, Fazhi; TANG, Ting; EP3476829; (2019); A1;,
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In the chemical reaction process, reaction time, type of solvent, can easily affect the result of the reaction, thereby determining the yield and properties of the reaction product. An updated downstream synthesis route of 134450-56-9 as follows. 134450-56-9

General procedure: The synthesis was largely adopted from literature. (reference 4) To a solution ofcarbazole (2.0 g, 12.0 mmol, 1 equiv.) in dry THE (40 mL) at room temperature wasportionwise added sodium hydride (60% in mineral oil, 0.96 g, 24.0 mmol, 2 equiv.). The suspension was stirred under nitrogen protection for 15 minutes. 4,5- difluorophthalonitrile (1.2 g, 0.72 mmol, 0.6 equiv.) was added. The colour of the suspension changed from milky to red immediately and it was allowed to stir for further3 h. Green emission (upon excitation with 365 nm UV light) slowly developed during the course of the reaction. The suspension was then slowly added to ice water and then the mixture was extracted with DCM (3 x 25 mL). The combined organic layers were dried with anhydrous sodium sulfate and concentrated under reduced pressure. The crude mixture was purified by flash column chromatography using DCM : Hexanes= 3 : 2 as eluent to afford the title compound. Green solid. Yield: 74%. R: 0.39 (EtOAc Hexanes = 1:4 on silica). Mp: 332-333C. 1H NMR (300 MHz, CDCI3) oe (ppm): 8.33 (s, 2 H), 7.82-7.79 (m, 4 H), 7.16-7.06 (m, 12 H). 13C NMR (76 MHz, CDCI3) oe (ppm):138.4, 138.2, 135.5, 126.2, 124.3, 121.7, 120.4, 114.7, 114.5, 109.0.

According to the analysis of related databases, 134450-56-9, the application of this compound in the production field has become more and more popular.

Reference:
Patent; UNIVERSITY COURT OF THE UNIVERSITY OF ST ANDREWS; ZYSMAN-COLMAN, Eli; WONG, Michael Yin; (74 pag.)WO2016/174377; (2016); A1;,
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172921-32-3, A common compound: 172921-32-3, name is 2,5-Difluoro-4-nitrobenzonitrile, belongs to nitriles-buliding-blocks compound, it can change the direction of chemical reaction, and react with certain compounds to generate new functional products. A new synthetic method of this compound is introduced below.

Add 680 g of cyanide to the reaction vessel. 15% sodium hydroxide solution 340 g, Stir, heat, reflux at around 95, GC tracking until the reaction is over, slightly cold, Add hydrochloric acid under stirring to adjust the pH of the solution to about 1, slightly cold, Pour into ice water to precipitate a solid product, suction filtration, and dry. Obtained 518 g of a white solid. The content is more than 97%, and the yield is 76%.

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, 2,5-Difluoro-4-nitrobenzonitrile, other downstream synthetic routes, hurry up and to see.

Reference:
Patent; Changzhou University; Chen Xingquan; Dong Yanmin; (5 pag.)CN109369412; (2019); A;,
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118431-88-2,Some common heterocyclic compound, 118431-88-2, name is 3-Cyclopropyl-3-oxopropanenitrile, molecular formula is C6H7NO, 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 3-cyclopropyl-3-oxopropaneni- trile (0.74 g, 7.6 mmol) and quinolin-5-yl-hydrazine (prepared from Example 4 step a, 1.0 g, 6.3 mmol) in ethanol (5 mE) was heated at 80 C. for 3 h with stirring. Afier cooling to room temperature, 20% aqueous sodium hydroxide (1.5 mE) was added to the reaction mixture and heated at 70 C. for 3 h. The mixture was cooled to room temperature and concentrated in vacuo. The crude residue was dissolved in 1:1 dichloromethane/methanol (40 mE) and the phases were separated. The organic layer was dried (Na2504), and filtered through a pad of Celite. The filtrate was concentrated in vacuo and the crude material was purified by flash chromatography (5i02, 1-10% methanol containing 10% ammonium hydroxide in dichloromethane) to give the desired product (0.80 g, 3.2 mmol, 50%).

These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route 118431-88-2, its application will become more common.

Reference:
Patent; ChemoCentryx, Inc.; Cappel, Markus; (83 pag.)US2018/9797; (2018); A1;,
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In the next few decades, the world population will flourish. As the population grows rapidly and people all over the world use more and more resources, all industries must consider their environmental impact. 621-03-4, name is 2-Cyano-N-phenylacetamide belongs to nitriles-buliding-blocks compound, it is a common compound, a new synthetic route is introduced below. 621-03-4

General procedure: To a solution of cyclohexan-1,4-dione (1.12 g, 0.01 mol) in1,4-dioxane (40 mL) containing triethylamine (0.50 mL) each of elemental sulfur (0.32 g, 0.01 mol) and any of 2-cyano-N-phenylacetamide (1.60 g, 0.01 mol), N-(4-chlorophenyl)-2-cyanoacetamide (1.94 g, 0.01 mol) or N-(4-nitrophenyl)-2-cyanoacetamide (2.05 g, 0.01 mol) wereadded. The reaction mixture was heated under reflux for 2 hthen poured onto ice/water containing few drops of hydrochloricacid. The formed solid product, in each case, wascollected by filtration.2-Amino-6-oxo-N-phenyl-4,5,6,7-tetrahydrobenzo[b]thiophene-3-carboxamide (3a) Orange crystals (ethanol), yield70% (2.00 g), m.p. 183-185 C; (IR (KBr) numax 3493, 3329,3055, 2984, 1689, 1639, 1583; 1H NMR (DMSO-d6, 200MHz): delta = 8.28 (s, 1H, D2O exchangeable, NH), 7.48-7.24(m, 4H, C6 H4), 4.85 (s, 2H, D2O exchangeable, NH2), 2.79(s, 2H, CH2), 1.92-1.65 (2t, 4H, 2CH2), 13C NMR (DMSOd6,75MHz): delta = 166.2, 164.8 (2CO), 141.8, 140.2, 138.4,133.5, 127.2, 124.8, 122.5, 120.5 (C6H5, thiophene C),40.0, 38.8, 18.6 (3CH2); EIMS: m/z 286 [M]+ (26%);analysis calcd for C15H14N2O2S (286.35): C, 62.96; H,4.93; N, 9.78; S, 11.20%. Found: C, 63.19; H, 4.69; N,9.84; S, 11.36%.

The synthetic route of 621-03-4 has been constantly updated, and we look forward to future research findings.

Reference:
Article; Mohareb, Rafat M.; Al-Omran, Fatima; Ibrahim, Rehab A.; Medicinal Chemistry Research; vol. 27; 2; (2018); p. 618 – 633;,
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922728-21-0, The chemical industry reduces the impact on the environment during synthesis 922728-21-0, name is 4,4-Difluorocyclohexanecarbonitrile, I believe this compound will play a more active role in future production and life.

[(4,4-Difluorocyclohexyl)methyI]amineLiAlH4 (2.20 g, 57.9 mmol) was added to a solution of 4,4- difluorocyclohexanecarbonitrile (6.10 g, 42.0 mmol) in THF (250 mL) at ambient temperature. The reaction mixture was refluxed to 75C and stirred for four hours. The reaction mixture was cooled to 00C and slowly quench by addition of MeOH over 1 hour. The mixture was filtered over a Celite pad and the filtrate was concentrated. The product was purified by distillation (65C/15 mmHg) to afford the title compound as a colorless liquid. Yield: 2.55 g (40%). 1H NMR (400 MHz, CHLOROFORM-D): delta 1.17 – 1.46 (m, 3 H), 1.52 – 1.94 (m, 2 H), 2.03 – 2.32 (m, 2 H), 2.57 – 2.70 (m, 2 H).

The chemical industry reduces the impact on the environment during synthesis 4,4-Difluorocyclohexanecarbonitrile. I believe this compound will play a more active role in future production and life.

Reference:
Patent; ASTRAZENECA AB; WO2007/13848; (2007); A1;,
Nitrile – Wikipedia,
Nitriles – Chemistry LibreTexts