Category: 31108-57-3

Synthetic Route of 31108-57-3,Some common heterocyclic compound, 31108-57-3, name is 1H-Pyrazole-4-carbonitrile, molecular formula is C4H3N3, 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 7(2R)-4-(4-cvano-1 H-pyrazol-1 -yl)-N-hvdroxy-2-methyl-2-Step A: (2R)-4-(4-cvano-1 H-pyrazol-1 -yl)-2-methyl-2-(methylsulfonyl)butanoic acid To a solution of 4-cyanopyrazole (0.150 g, 1 .61 mmol, 1 eq) in acetonitrile (10 mL) was added cesium carbonate (1 .31 g, 4.03 mmol, 2.5 eq), sodium iodide (0.048 mg, 0.322 mmol, 0.2 eq) and (R)-ethyl 4-bromo-2-methyl-2- (methylsulfonyl)butanoate (0.555 g, 1 .93 mmol, 1 .2 eq). The mixture was heated at 50 C overnight. The reaction mixture was cooled to room temperature and was filtered via Buchner funnel, and eluted with EtOAc. The filtrate was concentrated under reduced pressure and was diluted with up in tetrahydrofuran (5 mL) and water (5 mL). Lithium hydroxide (0.1 16 g, 4.83 mmol, 3 eq) was added, and the reaction mixture was allowed to stir at room temperature for four hours. The reaction mixture was concentrated under reduced pressure, diluted with ethyl acetate (10mL), and concentrated again. This yielded (2R)-4-(4-cyano-1 H-pyrazol-1 -yl)-2-methyl-2- (methylsulfonyl)butanoic acid as a yellow oil, which was carried on crude in the next step. LC-MS M+H+ 272.2.

The synthetic route of 31108-57-3 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; PFIZER INC.; BROWN, Matthew F.; CHEN, Jinshan Michael; MELNICK, Michael; MONTGOMERY, Justin I.; REILLY, Usa; WO2012/137099; (2012); A1;,
Pyrazole – Wikipedia,
Pyrazoles – an overview | ScienceDirect Topics

Application of 31108-57-3, 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 31108-57-3 as follows.

Synthesis of II-B14 To a solution of II-B13 (220 mg, 0.53 mmol) in acetone (3 mL) was added 4-cyano-pyrazole (197 mg, 2.1 mmol) and K2C03 (292 mg, 2.1 mmol). After stirring at 25C for 16 h, the reaction mixture was diluted with water (10 mL) and extracted with EtOAc (2 x 10 mL). The combined organic solution was concentrated and purified by prep-HPLC (Instrument: BF; Column: Xtimate C18 l50*25mm*5pm; Condition: water (0.225% FA)-ACN; Begin B: 50; End B: 70; Gradient Time (min): 7.5; 100%B Hold Time (min): 2; FlowRate (mL/min): 30), lyophilized and re-crystallized from MeCN/H20 (20 mL, 1 : 1) to give II-B14 (84 mg, 37%) as a solid. 1H NMR (400 MHz, CDCl3) dH, 7.84-7.78 (m, 2H), 5.07 (d, 7= 18.0 Hz, 1H), 4.95 (d, 7 = 18.6 Hz, 1H), 3.88-3.77 (m, 2H), 3.71 (dd, 7=3.6, 11.6 Hz, 1H), 3.27 (t, 7= 11.6 Hz, 1H), 2.72 (dd, 7=3.6, 11.2 Hz, 1H), 1.89-1.69 (m, 5H), 1.55-1.24 (m, 15H), 1.16-0.99 (m, 6H); LC-ELSD/MS purity 99%, MS ESI calcd. for C25H34N302 [M+H-H20]+ 408.3, found 408.2.

According to the analysis of related databases, 31108-57-3, the application of this compound in the production field has become more and more popular.

Reference:
Patent; SAGE THERAPEUTICS, INC.; ROBICHAUD, Albert, Jean; SALITURO, Francesco, G.; BLANCO-PILLADO, Maria, Jesus; LA, Daniel; HARRISON, Boyd, L.; (206 pag.)WO2019/140272; (2019); A1;,
Pyrazole – Wikipedia,
Pyrazoles – an overview | ScienceDirect Topics

Application of 31108-57-3, 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. 31108-57-3, name is 1H-Pyrazole-4-carbonitrile, This compound has unique chemical properties. The synthetic route is as follows.

Intermediate 4: 3,5-dibromo-lH-pyrazole-4-carbonitrile To lH-pyrazole-4-carbonitrile (6.76 g, 52.2 mmol) purchased from Aldrich (catalog number CDS008901) were added ethanol (150 mL) and water (225 mL). Then sodium acetate (29.1 g, 355 mmol) was added and the mixture was stirred until solids completely dissolved. Then bromine (10.75 mL, 209 mmol) was added dropwise. After 2 hours the reaction was complete. The reaction was diluted with water then extracted with DCM (3X150ml). The combined organic phases were washed with a saturated aqueous solution of sodilum thiosulfate (Na2S203). Poor layer seperation was observed in separating funnel, so water was added until DCM layer was in the bottom. The organic phase was then dired over MgS04, filtered and concentrated to form a solid. Purification: the solid was first dissolved in EtOAc. When the entire solid was dissolved, additional EtOAc was added to almost double the starting volume. Then hexane was added until solution turned slightly cloudy. After 30 min decantation, the small amount of precipitate formed in the flask was filtered, a dark brown oil left on the filter. The much lighter amber color solution that filtered though was then concentrated and contained mostly the desired product of 3,5-dibromo-lH-pyrazole-4-carbonitrile (8.9 g, 35.5 mmol, 68.0 % yield), it was used without further purification. No proton in the structure (only NH), no NMR spectrum. LCMS: the compound does not ionize.

The chemical industry reduces the impact on the environment during synthesis 1H-Pyrazole-4-carbonitrile. I believe this compound will play a more active role in future production and life.

Reference:
Patent; GLAXOSMITHKLINE INTELLECTUAL PROPERTY DEVELOPMENT LIMITED; NEW YORK UNIVERSITY SCHOOL OF MEDICINE; ALONSO PADILLA, Julio; CHARNLEY, Adam Kenneth; COTILLO TORREJON, Ignacio; ELBAN, Mark; HUGHES, Terry Vincent; KESSLER, Albane Marie; KNAPP-REED, Beth Anne; LIAN, Yiqian; MARTIN, Jose Julio; PENA URQUIZA, Imanol; RODRIGUEZ FERNANDEZ, Ana; (37 pag.)WO2016/55607; (2016); A1;,
Pyrazole – Wikipedia,
Pyrazoles – an overview | ScienceDirect Topics

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. 31108-57-3, name is 1H-Pyrazole-4-carbonitrile belongs to pyrazoles-derivatives compound, it is a common compound, a new synthetic route is introduced below. Recommanded Product: 1H-Pyrazole-4-carbonitrile

To a solution of 2-chloro-N-(2,4-dimethoxybenzyl)-5-nitrobenzenesulfonamide (15.0 g, 38.8 mmol) in acetonitrile (450 mL) were added 1H-pyrazole-4-carbonitrile (5.41 g, 93.1 mmol) and powdered potassium carbonate (16.1 g, 116 mmol) and it was stirred overnight at 10000. The reaction mixture was concentrated in vacuo and the residue was extractedwith ethyl acetate and water. Pure title compound precipitated and was filtered off (9.09 g20.5 mmol, 53 % yield, 97 % purity), The organic phase was washed with brine and dried over sodium sulfate. Concentration in vacuo led to further crude title compound (9.11 g., app. 60 % purity).LC-MS (Method B): Rt = 1.17 mm; MS (ESIneg): m/z = 442 [M-H]1HNMR (400MHz, DMSO-d6) oe [ppm]: 3.53 (s, 3H), 3.64 (s, 3H), 4.08 (s, 2H), 6.20 (d,1H), 6.29 (dd, 1H), 7.07 (d, 1H), 7.89 (d, 1H), 8.12 (br s, 1H), 8.30 (br s, 1H), 8.41 -8.54 (m, 2H), 9.17 (brs, 1H).

The synthetic route of 31108-57-3 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; BAYER PHARMA AKTIENGESELLSCHAFT; WERNER, Stefan; MESCH, Stefanie; CLEVE, Arwed; BRAeUER, Nico; HERBERT, Simon, Anthony; KOCH, Markus; DAHLLOeF, Henrik; OSMERS, Maren; HARDAKER, Elizabeth; LISHCHYNSKYI, Anton; (673 pag.)WO2017/191000; (2017); A1;,
Pyrazole – Wikipedia,
Pyrazoles – an overview | ScienceDirect Topics

Synthetic Route of 31108-57-3, 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. 31108-57-3, name is 1H-Pyrazole-4-carbonitrile, This compound has unique chemical properties. The synthetic route is as follows.

To a solution of II-C4 (110 mg, 0.3 mmol) and lH-pyrazole-4-carbonitrile (48.1 mg, 0.5 mmol) in acetone (5 mL) was added K2C03 (71.3 mg, 0.52 mmol). The reaction mixture was stirred at 20C for 16 hrs. The reaction mixture was quenched with saturated NH4Cl (30 mL) and extracted with EtOAc (3 x 20 mL). The combined organic phase was washed with saturated brine (20 mL), dried over anhydrous Na2S04, filtered and concentrated to give the product (100 mg) as an oil. The product was purified by flash column (0-30% of EtOAc in PE) to give II-C5 (52.8 mg, 59%) as a solid. (2650) 1H NMR (400 MHz, CDCI3) dH 7.85 (s, 1H), 7.81 (s, 1H), 4.95 (dd, J= 18.0, 48.8 Hz, 2H), 2.59 (t, J= 8.4 Hz, 1H), 2.26-2.15 (m, 1H), 2.08-2.02 (m, 1H), 1.91-1.84 (m, 1H), 1.82-1.58 (m, 7H), 1.53-1.34 (m, 4H), 1.33-1.07 (m, 12H), 1.00-0.88 (m, 1H), 0.87-0.77 (m, 1H), 0.76 (s, 3H), 0.65 (s, 3H); ELSD, purity 99%; MS ESI calcd. for C^HssONs [M+H-H20]+ 420, found 420.

The chemical industry reduces the impact on the environment during synthesis 1H-Pyrazole-4-carbonitrile. I believe this compound will play a more active role in future production and life.

Reference:
Patent; SAGE THERAPEUTICS, INC.; ROBICHAUD, Albert, Jean; SALITURO, Francesco, G.; BLANCO-PILLADO, Maria, Jesus; LA, Daniel; HARRISON, Boyd, L.; (646 pag.)WO2019/126761; (2019); A1;,
Pyrazole – Wikipedia,
Pyrazoles – an overview | ScienceDirect Topics

Reference of 31108-57-3, The chemical industry reduces the impact on the environment during synthesis 31108-57-3, name is 1H-Pyrazole-4-carbonitrile, I believe this compound will play a more active role in future production and life.

To a solution of II-H18 (150 mg, 0.39 mmol) in acetone (3 mL) were added lH-pyrazole-4- carbonitrilev (43.6 mg, 0.47 mmol) and K2CO3(l08 mg, 0.78 mmol). After stirring at 25C for 14 h, the mixture was diluted with water (20 mL) and extracted with EtOAc (2 x 30 mL). The organic solution was separated, dried over Na2S04, filtered and concentrated. The residue was purified by flash column (20-50% of EtOAc in PE) to give II-H19 (76 mg) as a solid. The solid was further purified by HPLC separation (column: Xtimate C18 (2903) l50*25mm*5um, gradient: 67-87% B (water(0.225%FA)-ACN), flow rate: 25 mL/min) to give II-H19 (43 mg) as a solid. (2904) 1H NMR (400 MHz, CDC13) dH 7.86 (s, 1 H), 7.81 (s, 1 H), 5.05-4.84 (m, 2 H), 2.66-2.57 (m, 1 H), 2.30-2.13 (m, 1 H), 2.10-2.05 (m, 1 H), 1.90-1.95 (m, 7H), 1.53-1.40 (m, 3H), 1.36- 1.22 (m, 8 H), 1.14 – 0.80 (m, 4 H), 0.82 – 0.72 (m, 1 H), 0.68 (s, 3 H); LC-ELSDE/MS purity 99%, MS ESI calcd. for C24H33N302 [M+H]+396.2, found 396.2.

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, 1H-Pyrazole-4-carbonitrile, other downstream synthetic routes, hurry up and to see.

Reference:
Patent; SAGE THERAPEUTICS, INC.; ROBICHAUD, Albert, Jean; SALITURO, Francesco, G.; BLANCO-PILLADO, Maria, Jesus; LA, Daniel; HARRISON, Boyd, L.; (646 pag.)WO2019/126761; (2019); A1;,
Pyrazole – Wikipedia,
Pyrazoles – an overview | ScienceDirect Topics

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. 31108-57-3, name is 1H-Pyrazole-4-carbonitrile, This compound has unique chemical properties. The synthetic route is as follows., name: 1H-Pyrazole-4-carbonitrile

General procedure: The appropriate carboxylic acid (1.0 equiv) was treated with oxalylchloride (1.1 equiv) in CH2Cl2 (0.5 M) at 0 C. The reaction mixture wasstirred at room temperature for 1 h. The solvent was removed under N2and the acid chloride (1 equiv) was dissolved in anhydrous CH2Cl2(0.5 M). The appropriate pyrazole (1.0 equiv) was dissolved in CH2Cl2(0.5 M) and cooled to 0 C. The acid chloride (1 equiv) in CH2Cl2 (0.5 M) was added dropwise and the reaction mixture was stirred atroom temperature for 3 h. The mixture was diluted with EtOAc, washedwith saturated aqueous NaCl, and dried over Na2SO4. Evaporationunder reduced pressure yielded the crude product that was purified byflash chromatography (SiO2).

Chemical properties determine the actual use. Each compound has specific chemical properties and uses. We look forward to more synthetic routes in the future to expand reaction routes of 31108-57-3.

Reference:
Article; Otrubova, Katerina; Chatterjee, Shreyosree; Ghimire, Srijana; Cravatt, Benjamin F.; Boger, Dale L.; Bioorganic and Medicinal Chemistry; vol. 27; 8; (2019); p. 1693 – 1703;,
Pyrazole – Wikipedia,
Pyrazoles – an overview | ScienceDirect Topics

Related Products of 31108-57-3, These common heterocyclic compound, 31108-57-3, name is 1H-Pyrazole-4-carbonitrile, 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: The appropriate carboxylic acid (1.0 equiv) was treated with oxalyl chloridie (1.1 equiv) in CH2Cl2 (0.5 M) at 0 C. The reaction mixture was stirred at room temperature for 1 h. The solvent was removed under N2 and the acid chloride was redissolved in anhydrous CH2Cl2 (0.5 M). The appropriate pyrazole (1.0 equiv) was dissolved in CH2Cl2 and cooled to 0 C. The acid chloride was added dropwise and the reaction mixture was stirred at room temperature for 3 h. The mixture was diluted withEtOAc, washed with saturated aqueous NaCl, and dried over Na2SO4. Evaporation under reduced pressure yielded the crude product that was purified by flash chromatography(SiO2).

Statistics shows that 1H-Pyrazole-4-carbonitrile is playing an increasingly important role. we look forward to future research findings about 31108-57-3.

Reference:
Article; Otrubova, Katerina; Srinivasan, Venkat; Boger, Dale L.; Bioorganic and Medicinal Chemistry Letters; vol. 24; 16; (2014); p. 3807 – 3813;,
Pyrazole – Wikipedia,
Pyrazoles – an overview | ScienceDirect Topics

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 31108-57-3 as follows. Formula: C4H3N3

EXAMPLE P7: Preparation of 1-[6-[3-chloro-6-(trifluoromethvnpyrazolo[4,3-clpyridin-2-yll-5- ethylsulfonyl-2-pyridyllpyrazole-4-carbonitrile (compound P10): (0692) (0693) To a solution of 3-chloro-2-(6-chloro-3-ethylsulfonyl-2-pyridyl)-6-(trifluoromethyl)pyrazolo[4,3-c]pyridine (425 mg, 1 mmol) in N,N-dimethylformamide (4 mL) was added dipotassium carbonic acid (140 mg, 1 mmol), followed by 1 H-pyrazole-4-carbonitrile (93mg, 1 mmol). The mixture was stirred at room temperature for 3hrs. The reaction was diluted with ice water (20 ml), extracted with ethyl acetate (2×40 ml), the combined organic layers washed with water and brine, dried over sodium sulfate, filtered and concentrated under reduced pressure. The crude product was purified by combiflash (silica gel, 40% EA-cyclohexane) to afford 1-[6-[3-chloro-6-(trifluoromethyl)pyrazolo[4,3-c]pyridin-2-yl]- 5-ethylsulfonyl-2-pyridyl]pyrazole-4-carbonitrile (compound P10) as a solid, mp 251-253C. LCMS (method 3): 482/484 (M+H)+, retention time 1.50 min.

According to the analysis of related databases, 31108-57-3, the application of this compound in the production field has become more and more popular.

Reference:
Patent; SYNGENTA PARTICIPATIONS AG; MUEHLEBACH, Michel; JUNG, Pierre, Joseph, Marcel; EDMUNDS, Andrew; SIKERVAR, Vikas; RAWAL, Girish; SEN, Indira; HALL, Roger, Graham; (117 pag.)WO2017/134066; (2017); A1;,
Pyrazole – Wikipedia,
Pyrazoles – an overview | ScienceDirect Topics

Reference of 31108-57-3, 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. 31108-57-3, name is 1H-Pyrazole-4-carbonitrile, This compound has unique chemical properties. The synthetic route is as follows.

Synthesis of II-A13b To a solution of II-A12b (200 mg, 0.5 mmol) in acetone (3 mL) was added 4-cyanopyrazole (69.9 mg, 0.8 mmol) and K2C03 (345 mg, 2.5 mmol). The mixture was stirred at 25C for 16 hrs. To the mixture was added water (20 mL) and the mixture was extracted with EtOAc (2 x 20 mL). The organic layer was separated, concentrated and purified by flash column (0781) (25-60% EtOAc in PE) to give II-A13b (100 mg). The material (100 mg) was purified by HPLC separation to give II-A13b (4 mg, 2%) as a solid. (0782) 1H NMR (400 MHz, CDCf) dH 7.85-7.80 (m, 2H), 5.38-5.09 (m, 2H), 4.05 (t, J =1.6 Hz, 1H), 3.98 (s, 1H), 3.67 (dd, J= 8.0, 12.0 Hz, 1H), 1.95-1.66 (m, 7H), 1.52-1.37 (m, 8H), 1.35-1.19 (m, 7H), 1.17-1.00 (m, 1H), 0.86 (s, 3H); LC-ELSD/MS purity 99%, MS ESI calcd. for C^^NsOs [M +H]+ 412.2, found 412.2.

The chemical industry reduces the impact on the environment during synthesis 1H-Pyrazole-4-carbonitrile. I believe this compound will play a more active role in future production and life.

Reference:
Patent; SAGE THERAPEUTICS, INC.; ROBICHAUD, Albert, Jean; SALITURO, Francesco, G.; BLANCO-PILLADO, Maria, Jesus; LA, Daniel; HARRISON, Boyd, L.; (206 pag.)WO2019/140272; (2019); A1;,
Pyrazole – Wikipedia,
Pyrazoles – an overview | ScienceDirect Topics