Month: January 2021

Synthetic Route of 2032-34-0, A common heterocyclic compound, 2032-34-0, name is 3,3-Diethoxypropanenitrile, molecular formula is C7H13NO2, 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.

a) (2E)-2-[bis(methyloxy)methyl]-3-[2-methyl-3-(trifluoromethyl)phenyl]-2-propenenitrile To a solution of 2-methyl-3-(trifluoromethyl)benzaldehyde (3.0 g, 16 mmol) and 3,3-bis(ethyloxy)propanenitrile (2.3 g, 20 mmol) in methanol (10 mL) was added a 25% sodium methoxide in methanol over 20 minutes. The mixture was stirred at room temperature overnight. Most of solvent was evaporated in vacuo and the residue was dissolved with ethyl acetate (30 mL) and water (15 mL). Two layers were separated. Organic layer was separated, washed with brine (15 mL), dried and solvent was evaporated in vacuo. The residue was then purified to give product. (3.66 g, 64%); 1H NMR (400 MHz, DMSO-d6) delta ppm 2.40 (s, 3H) 2.94 (m, J=11.37 Hz, 1H) 3.08 (m, J=4.80 Hz, 1H) 3.20 (s, 1H) 3.43 (d, J=10.36 Hz, 1H) 3.42 (d, J=11.12 Hz, 6H) 3.45-3.52 (m, 1H) 4.60 (d, J=4.80 Hz, 1H) 7.39 (t, J=7.71 Hz, 1H) 7.59 (dd, J=17.18, 7.83 Hz, 2H).

The synthetic route of 2032-34-0 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; GlaxoSmithKline LLC; Lin, Hong; Luengo, Juan Ignacio; Moore, Michael Lee; Qu, Junya; Rivero, Ralph A.; Tedesco, Rosanna; Yu, Hongyi; US9096605; (2015); B2;,
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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. 6011-14-9, name is 2-Aminoacetonitrile hydrochloride, A new synthetic method of this compound is introduced below., SDS of cas: 6011-14-9

In a 250 mL three-necked flask, 10 g of maleic anhydride, 9.5 g of aminoacetonitrile hydrochloride, 50 ml of acetonitrile was added, and triethylamine was added dropwise at a temperature of 0 to 10 C.Thereafter, the reaction solution was cooled to room temperature, and then the acetonitrile was distilled off under reduced pressure.Thereafter, 30 ml of ethyl acetate and 25 ml of water were added to the residue. After the stirring, the liquid separation operation was carried outAnd then the water layer is removed.To the organic layer, 25 ml of a saturated aqueous solution of sodium chloride was added, followed by a liquid separation operation after stirring, and then the aqueous layer was removed. There will be several layers of distillation under reduced pressure.To give 12.8 g of an oil (compound 2) in 81% yield, volume 1 (purity: 99.21%).

The synthetic route of 6011-14-9 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; University of Jinan; Zheng Gengxiu; Yang Liu; Ma Zhijia; Wang Wei; Fu Kai; (5 pag.)CN104817511; (2017); B;,
Nitrile – Wikipedia,
Nitriles – Chemistry LibreTexts

5866-98-8, name is 2,6-Dichloro-3-nitrobenzonitrile, 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. category: nitriles-buliding-blocks

Example 4 Synthesis of 2-(2,6-Dichlorophenylamino)-1,6,7-trimethyl-1,8-dihydro-imidazo[4,5-]isoquinoline-9-one A solution of 2,6-dichloro-3-nitrobenzonitrile (98.7 g, 0.455 mol) in EtOAc (910 mL) was cooled to 5 C. 40% Aqueous methylamine (79.5 mL, 1.14 mol) was added with vigorous mechanical stirring, keeping the temperature at 10-15 C. After addition was complete, stirring was continued for 3 h at the same temperature. More methylamine (16 mL, 0.23 mol) was added, and the mixture stirred for a further 1.5 h at room temperature. Water (300 mL) was added, followed by hexane (450 mL). The mixture was stirred for 15 min, filtered, and the solid washed with water and MeOH, to give 6-chloro-2-methylamino-3-nitrobenzonitrile (80.3 g, 83%), mp 167-170 C.

The synthetic route of 5866-98-8 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; Boehringer Ingelheim Pharmaceuticals, Inc.; US6506769; (2003); B2;,
Nitrile – Wikipedia,
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Related Products of 53312-81-5, As we all know, there are many different methods for the synthesis of a compound, and people can choose the synthesis method that suits their own laboratory according to the actual situation. 53312-81-5 name is 5-Amino-2-fluorobenzonitrile, This compound is widely used in many fields, so it is necessary to find a new synthetic route. The downstream synthesis method of this compound is introduced below.

Ethyl 4-[ [(1 R)-2,2-difluoro- 1 -methyl-propyl] sulfamoyl] -3 -fluoro- 1 -methyl-pyrrole-2-carboxylate (150mg, 0.42 mmol) and 5-amino-2-fluorobenzonitrile (75.9 mg, 0.54 mmol) were dissolved in THF (5 mL). Lithium bis(trimethylsilyl)amide (1.67 mL, 1 M, 1.67 mmol) was added drop wise and the reaction mixture was stirred at room temperature for 30 minutes. The reaction mixture was quenched with sat. NH4C1 (aq;, 5 mL). The organic layer was removed and the aqueous layer extracted with CH2C12 (2 x 5 mL). The combined organic layers were evaporated to dryness andthe residue was purified by silica gel chromatography (ethyl acetate in heptane 0 to 100% and again with ethyl acetate in heptane 0 to 60%). The desired fractions were evaporated to dryness, the resulting residue was dissolved in refluxing isopropanol (7 mL) and sonicated to afford a suspension. The white solids were filtered and washed with isopropanol (1 mL) to afford compound 317 (115 mg) as off white powder. ?H NMR (400 MHz, DMSO-d6) oe ppm 1.07 (d,J6.8 Hz, 3 H), 1.58 (t, J19.1 Hz, 3 H), 3.45 – 3.61 (m, 1 H), 3.81 (s, 3 H), 7.48 – 7.54 (m, 1 H),7.54 (t, J9.2 Hz, 1 H), 7.96 (ddd, J9.2, 4.9, 2.6 Hz, 1 H), 8.04 – 8.37 (m, 1 H), 8.17 (dd, J=5.7, 2.6 Hz, 1 H), 10.32(br. s., 1 H). Method B: Rt: 0.98 minmlz: 431.1 (M-H)Exactmass: 432.1.

At the same time, in my other blogs, there are other synthetic methods of this type of compound, 5-Amino-2-fluorobenzonitrile, and friends who are interested can also refer to it.

Reference:
Patent; JANSSEN R&D IRELAND; VANDYCK, Koen; HACHE, Geerwin, Yvonne, Paul; LAST, Stefaan, Julien; MC GOWAN, David, Craig; ROMBOUTS, Geert; VERSCHUEREN, Wim, Gaston; RABOISSON, Pierre, Jean-Marie, Bernard; WO2014/184350; (2014); A1;,
Nitrile – Wikipedia,
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Application of 4553-07-5, 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. 4553-07-5, name is Ethyl 2-cyano-2-phenylacetate belongs to nitriles-buliding-blocks compound, it is a common compound, a new synthetic route is introduced below.

To the suspension of ethyl phenylcyanoacetate (1.0 g, 5.3 mmol) in anhydrous ether (200 mL) was added lithium aluminum hydride at 0 C. The mixture was stirred at 0 C. for 18 h. After adding water (1 equiv.), 15% sodium hydroxide (1 equiv.) and water (3 equiv.) to the above solution, the precipitation was removed by filtration. The filtrate was concentrate to dry by lyophilization. Flash chromatography (Merck Silica gel 60, 70-230 mesh, 0%-10% methanol in methylene chloride (0.1% NH4OH) in 30 min afforded 3-hydroxy-2-phenyl-propylamine (0.16 g, 20%).

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, Ethyl 2-cyano-2-phenylacetate, other downstream synthetic routes, hurry up and to see.

Reference:
Patent; Chen, Li; Chen, Shaoqing; US2006/4045; (2006); A1;,
Nitrile – Wikipedia,
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Reference of 75279-55-9,Some common heterocyclic compound, 75279-55-9, name is 2-Chloro-6-fluorophenylacetonitrile, molecular formula is C8H5ClFN, 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.

Step 1–Preparation of alpha-[2-(4-chlorophenyl)ethyl]-2-chloro-6-fluorophenylacetonitrile A 3 neck 200 ml round bottom flask was charged with 7.5 gms of 60% NaH (0.187 mole, 1.5 eq.), washed three times with 25 ml hexanes, in 60 ml of 2:1 toluene:DMF. To this was added 21.2 gms (0.125 mole, 1.0 eq.) of 2-chloro-6-fluorophenylacetonitrile dropwise over 0.5 hour in 40 ml of 2:1 toluene:DMF. The reaction was stirred for 20 minutes at 10 C. then at room temperature for 1 hour after which 32.1 gms of 2-(4-chlorophenyl)ethyl methanesulfonate (0.137 mole, 1.1 eq.) in 60 ml of 2:1 toluene:DMF was added dropwise over 1 hour. Approximately 70 ml of 2:1 toluene:DMF was added to permit constant stirring and the reaction was stirred for an additional 3.5 hours after which gas liquid chromatography indicated the reaction was complete. Then 50 ml of water was added, followed by 10 ml of 10% HCl and 300 ml of ether. The ether was washed with 100 ml of water which was extracted twice with 50 ml of ether then washed with water. The combined ethers were dried and concentrated to give 40.0 gms of crude product which was distilled under reduced pressure. 26.6 gms (69.8%) of product resulted having a boiling point of 175-185 C. at 1 mm Hg. NMR (90 MHz): 2.2-2.9(m, 4H), 4.2-4.4(t, 1H) and 7.0-7.4(m, 7H).

These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route 2-Chloro-6-fluorophenylacetonitrile, its application will become more common.

Reference:
Patent; Rohm and Haas Company; US5087635; (1992); A;,
Nitrile – Wikipedia,
Nitriles – Chemistry LibreTexts

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 21883-13-6 as follows. name: 4-Methoxy-2-methylbenzonitrile

Decanethiol (261 mg, 1.5 mmol) and t-BuOK (168 mg, 1.5 mmol) were added to a solution of 4-methoxy-2-methylbenzonitrile (147 mg, 1 mmol) in DMF (5 mL). The reaction mixture was stirred at 110 C for 3 h. The mixture was then diluted with water (30 mL) and extracted with EtOAc (10 mL x 3). The extracts were washed with brine (10 mL x 3), dried over Na2SO4, and concentrated under reduced pressure. The resulting residue was purified by silica gel column with (petroleum ether:EtOAc = 10:1) to provide 4-hydroxy-2-methylbenzonitrile (70 mg, yield: 52.6%). LC-MS (011): 134.70 [M+H]+; Rt: 1.44 min, Purity: 80% (254 nm).

According to the analysis of related databases, 21883-13-6, the application of this compound in the production field has become more and more popular.

Reference:
Patent; TEMPERO PHARMACEUTICALS, INC.; BALOGLU, Erkan; GHOSH, Shomir; LOBERA, Mercedes; SCHMIDT, Darby, R.; WO2013/19621; (2013); A1;,
Nitrile – Wikipedia,
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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 1953-99-7 as follows. Quality Control of 3,4,5,6-Tetrachlorobenzene-1,2-dicarbonitrile

General procedure: To a 250 mL flask was added 4-dodecathio-3,5,6-Trichlorophthalonitrile (4.3 g), 3,4,5,6-Tetrachlorophthalonitrile (8.0 g), Diazabicycloundec-7-ene (4.5 g),1-Pentanol (80 mL) was added and the solid was dissolved by heating,Zinc acetate (1.8g) And reflux while heating.After completion of the reaction,Removed, Purify by column chromatography.Dichloromethane was appropriately added to the obtained solid to dissolve the solid, followed by addition of methanol to crystallize the solid. The obtained solid was filtered and dried under vacuum to obtain a compound represented by the following Chemical Formula 4-1. To a 250 mL flask was added 4-dodecathio-3,5,6-Trichlorophthalonitrile (4.3 g)3,4,5,6-Tetrachlorophthalonitrile (8.0 g) Instead, 4-dodecathio-3,5,6-Trichlorophthalonitrile (8.6 g)3,4,5,6-Tetrachlorophthalonitrile (5.3 g)Was obtained in the same manner as in Synthesis Example 1, except thatTo obtain the indicated compound.

According to the analysis of related databases, 1953-99-7, the application of this compound in the production field has become more and more popular.

Reference:
Patent; Samsung SD I Co., Ltd.; Park, In Kul; Kim, Hyung Mook; Park, Chae Won; Sin, Myung Yeop; Lee, Young Gi; Jung, Uii Soo; (31 pag.)KR2016/47824; (2016); A;,
Nitrile – Wikipedia,
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1080-74-6, name is 2-(3-Oxo-2,3-dihydro-1H-inden-1-ylidene)malononitrile, 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. category: nitriles-buliding-blocks

To a degassed mixture of compound 9-3 (192 mg, 0.14 mmol), anhydrous chloroform (15 cm3) and pyridine (0.77 cm3) was added 2-(3-oxo-indan-1 – ylidene)-malononitrile (185 mg, 0.95 mmol). The solution was then degassed for a further 10 minutes and then stirred at 23 C for 160 minutes. Methanol (300 cm3) was added and after stirring for 20 minutes the solid was collected by filtration. The solid was then washed with methanol (3 x 10 cm3), acetone (3 x 10 cm3) and diethyl ether (2 x 10 cm3) to give compound 9 (179 mg, 75%) as a solid. 1H-NMR (400 MHz, CDCIs) 0.80 – 0.90 (12H, m), 1.18 – 1.43 (72H, m), 1.49 – 1.64 (8H, m), 2.48 – 2.60 (8H, m), 7.06 – 7.19 (16H, m), 7.53 (2H, s), 7.70 (2H, s), 7.73 – 7.83 (4H, m), 7.90 – 7.95 (2H, m), 8.65 – 8.70 (2H, m), 8.81 (2H, s).

The synthetic route of 1080-74-6 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; MERCK PATENT GMBH; MORSE, Graham; HEARD, Kane; MITCHELL, William; KROMPIEC, Michal; D’LAVARI, Mansoor; PRON, Agnieszka; (260 pag.)WO2019/52935; (2019); A1;,
Nitrile – Wikipedia,
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Application of 149793-69-1,Some common heterocyclic compound, 149793-69-1, name is 3-Fluoro-5-(trifluoromethyl)benzonitrile, molecular formula is C8H3F4N, 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: General procedure for nucleophilic substitution: A solution of 3-fluoro-5-trifluoromethyl-benzonitrile (1 eq) and the corresponding amine (3eq) in DMA was stirred at 145C during 3h. NaCl(aq) was added. The product was taken off into ethyl acetate. The organic layer was washed two times with water then dried over Na2S04 and evaporated under reduced pressure to give a white solid. 3 -(4-Methyl-imidazo 1- 1 -yl)-5 -trifluoromethyl-benzonitrile Yield: 74%. HPLC: 100% ESI-MS: [M+H]+= 252 Da.

These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route 3-Fluoro-5-(trifluoromethyl)benzonitrile, its application will become more common.

Reference:
Patent; ORIBASE PHARMA; CHEVE, Gwenael; DAYDE-CAZALS, Benedicte; FAUVEL, Benedicte; BORIES, Cedric; YASRI, Abdelaziz; WO2014/102376; (2014); A1;,
Nitrile – Wikipedia,
Nitriles – Chemistry LibreTexts