Month: February 2021

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. 6136-93-2, name is 2,2-Diethoxyacetonitrile belongs to nitriles-buliding-blocks compound, it is a common compound, a new synthetic route is introduced below. Product Details of 6136-93-2

Step 1 To a vial was added 2,2-diethoxyacetonitrile (XXVI)(1.0 g, 7.74 mmol)dissolved MeOH (7.74 mL)followed by addition of MeONa/MeOH (0.18 mL, 0.77 mmol)dropwise. The reaction was stirred at room temperature for 20 h. HOAc (44.3 muL, 0.77 mmol)was added until pH=7-8 (using pH strips). (4-Bromo-3-fluoro-phenyl)methanamine hydrochloride (XXVII)(1.86 g, 7.74 mmol)was added and stirred at 40 C. for 4 h. The solvent was removed under vacuum. Sulfuric acid (12.6 mL, 232.3 mmol)was added and stirred at 40 C. for 16 h. NH4OH (30.8 mL, 240.0 mmol)was added dropwise at 0 C. The solvent was removed under vacuum and the residue was purified by C18 silica gel (240 g)[0?50% H2O/MeCN (0.1% Formic acid)] to produce 6-bromo-7-fluoro-isoquinolin-3-amine (XXVIII)(1.33 g, 5.50 mmol, 71.1% yield)as an off-white solid. 1H NMR (499 MHz, DMSO-d6)delta ppm 6.07 (2H, s), 6.61 (1H, s), 7.76 (1H, d, J=9.33 Hz), 8.01 (1H, d, J=6.86 Hz), 8.80 (1H, s); ESIMS found for C9H6BrFN2 m/z 242.9 (81BrM+H).

The synthetic route of 6136-93-2 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; Samumed, LLC; KC, Sunil Kumar; Mak, Chi Ching; Eastman, Brian Walter; Cao, Jianguo; Bollu, Venkataiah; Mittapalli, Gopi Kumar; Chiruta, Chandramouli; (218 pag.)US2017/313682; (2017); A1;,
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Reference of 57381-51-8, 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. 57381-51-8 name is 4-Chloro-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.

4-Chloro-2-fluorobenzonitrile (200 mg, 1 .29 mmol) and Na2S (1 10 mg, 1 .41 mmol) were added into a microwave vial, DMF (1 mL) was charged into the mixture before stirring for 1 h at room temperature. 1 M NaOH solution was charged to pH 12 then washed by Et20 (3 x 10 mL, acedified mixture with 1 M HCI to pH 1 -2 and extracted with Et20 (3 x 10 mL), the combined extracts were washed by water (30 mL) and brine (20 mL), dried by MgS04, concentrate in vacuo to give a yellow solid (156 mg, 72%). H NMR (500 MHz, CDCI3) delta 4.14 (1 H, s, SH), 7.21 (1 H, d, J = 8.4 Hz, H-Ar), 7.42 (1 H, s, H-Ar), 7.52 (1 H, d, J = 8.3 Hz, H-Ar).

At the same time, in my other blogs, there are other synthetic methods of this type of compound, 4-Chloro-2-fluorobenzonitrile, and friends who are interested can also refer to it.

Reference:
Patent; ASTEX THERAPEUTICS LIMITED; CANCER RESEARCH TECHNOLOGY LIMITED; CHESSARI, Gianni; HOWARD, Steven; BUCK, Ildiko Maria; CONS, Benjamin David; JOHNSON, Christopher Norbert; HOLVEY, Rhian Sara; REES, David Charles; ST. DENIS, Jeffrey David; TAMANINI, Emiliano; GOLDING, Bernard Thomas; HARDCASTLE, Ian Robert; CANO, Celine Florence; MILLER, Duncan Charles; CULLY, Sarah; NOBLE, Martin Edward Maentylae; OSBORNE, James Daniel; PEACH, Joanne; LEWIS, Arwel; HIRST, Kim Louise; WHITTAKER, Benjamin Paul; WATSON, David Wyn; MITCHELL, Dale Robert; (293 pag.)WO2017/55860; (2017); 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 120351-94-2 as follows. name: 3-(2-Aminoethoxy)benzonitrile

Step 1: To a solution of 3-(2-aminoethoxy)benzonitrile (276 mg, 1 mmol, 1.0 equiv) in 5 mL of methanol at room temperature was added TEA (630 muL, 4.5 equiv) and 4-bromophthalic anhydride (227 mg, 1.0 equiv). After stirring at room temperature for 3 h, the solvent was evaporated and the residue was vacuum dried. The residue in 10 mL of pyridine was then treated with 12 mL of acetic anhydride at room temperature overnight. The volatile solvent was evaporated, and the residue was taken up with EtOAc, washed with H2O, dried over MgSO4 and column purified with 1:3 EtOAc/hexanes on silica gel to give 3-[2-(5-bromo-1,3-dioxoisoindolin-2-yl)ethoxy]benzonitrile in 84% yield. LRMS found for C17H12BrN2O3 (M+H)+: 371.05.

According to the analysis of related databases, 120351-94-2, the application of this compound in the production field has become more and more popular.

Reference:
Patent; Millennium Pharmaceuticals, Inc.; US2003/114448; (2003); A1;,
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54202-05-0, name is Methyl 4-cyanobicyclo[2.2.2]octane-1-carboxylate, 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. HPLC of Formula: C11H15NO2

Methyl 4-cyanobicyclo[2.2.2]octane-l-carboxylate (0.83 g, 4.3 mmol) was taken up in methanol (86 mL), H2O (35 mL) and 1 N HCl (8.6 mL) along with PtO2 H2O (430 mg). The resulting reaction was stirred at room temperature under 35 psi of H2 for 5 h. TLC indicated that the reaction was complete (elution: petroleum ethcr/EtOAc=3:l , I2 visualization). The reaction mixture was concentrated under reduced pressure. Saturated aqueous Na2CO3 solution (20 mL) was then added, and the resulting mixture was extracted with CH2Cl2 (50 mLx2). The combined organic layers were dried (Na2SO4) and concentrated under reduced pressure to afford methyl 4-(aminomethyl)bicyclo[2.2.2]octane- 1-carboxylate as an oil (0.76 g, yield: 89%). 1HNMR (400MHz, CD3OD) delta: 1.56 (6H, m), 1.85 (6H, m), 2.732 (2H, s), 3.654 (3H, s).

The synthetic route of 54202-05-0 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; SIRTRIS PHARMACEUTICALS, INC.; WO2008/100423; (2008); A1;,
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Synthetic Route of 64248-62-0,Some common heterocyclic compound, 64248-62-0, name is 3,4-Difluorobenzonitrile, molecular formula is C7H3F2N, 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.

3.6 mL (7.2 mmol) of trimethyl aluminum (2.0 M toluene solution) was dropwise added to a 10 mL of toluene containing 384 mg (7.17 mmol) of ammonium chloride at room temperature. After stirring for 1.5 hours, 1 g (7.1 mmol) of3,4-difluorobenzonitrile was added thereto and the resulting mixture was heated to EPO 85C for 9 hours. After completion of a reaction, the reaction solution was poured into100 mL of chloroform containing 200 g of silicagel and filtered off. The residue was washed with 200 mL of methanol and distillation was conducted to give 370 mg (2.36 mmol) of the title compound in a yield of 33%. [920] NMR: 1H-NMR(CD3OD) delta 7.87~7.82(1H, m), 7.72~7.7O(1H, m), 7.63~7.55(1H, m)[921] Mass(EI) 157(M++.)

These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route 3,4-Difluorobenzonitrile, its application will become more common.

Reference:
Patent; LG LIFE SCIENCES, LTD.; WO2006/104356; (2006); A1;,
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Related Products of 57381-49-4, 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. 57381-49-4 name is 2-Bromo-4-chlorobenzonitrile, 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.

General procedure: General Method 2A: Suzuki Coupling A flask which had been dried by heating and flushed with argon was initially charged with 1.0 eq. of the appropriate boronic acids, 1.0 eq. of the aryl bromide or aryl iodide, 3.0 eq. of potassium carbonate and 0.1 eq. of [1,1-bis(diphenylphosphino)ferrocene]palladium(II) chloride/monodichloromethane adduct or tetrakis(triphenylphosphine)palladium(0). The flask was then evacuated three times and in each case vented with argon. Dioxane (about 6 ml/mmol) was added, and the reaction mixture was stirred at 110 C. for a number of hours until substantially complete conversion had been achieved. The reaction mixture was then filtered through Celite and the filtrate was concentrated under reduced pressure. Water was added to the residue. After addition of ethyl acetate and phase separation, the organic phase was washed once with water and once with saturated aqueous sodium chloride solution, dried (sodium sulphate or magnesium sulphate), filtered and concentrated under reduced pressure. The crude product was then purified either by means of normal phase chromatography (eluent: cyclohexane/ethyl acetate mixtures or dichloromethane/methanol mixtures) or preparative RP-HPLC (water/acetonitrile gradient or water/methanol gradient). Example 2.1B 4-Chloro-2-(2,5-dimethoxypyridin-4-yl)benzonitrile According to General Method 2A, 7.87 g (95% purity, 40.86 mmol) of 2,5-dimethoxypyridin-4-ylboronic acid were reacted with 8.85 g (40.86 mmol) of 2-bromo-4-chlorobenzonitrile in the presence of [1,1-bis(diphenylphosphino)ferrocene]palladium(II) chloride/dichloromethane monoadduct. Yield: 6.23 g (92% purity, 51% of theory). LC/MS [Method 1]: Rt=1.08 min; MS (ESIpos): m/z=275 (M+H)+.

At the same time, in my other blogs, there are other synthetic methods of this type of compound, 2-Bromo-4-chlorobenzonitrile, and friends who are interested can also refer to it.

Reference:
Patent; BAYER PHARMA AKTIENGESELLSCHAFT; ROeHRIG, Susanne; HILLISCH, Alexander; STRAssBURGER, Julia; HEITMEIER, Stefan; SCHMIDT, Martina Victoria; SCHLEMMER, Karl-Heinz; TERSTEEGEN, Adrian; BUCHMUeLLER, Anja; GERDES, Christoph; SCHAeFER, Martina; TELLER, Henrik; JIMENEZ NUNEZ, Eloisa; SCHIROK, Hartmut; KLAR, Juergen; LOBELL, Mario; (39 pag.)US2017/283412; (2017); A1;,
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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. 134997-74-3, name is 3-Oxo-3,4-dihydro-2H-benzo[b][1,4]oxazine-6-carbonitrile, This compound has unique chemical properties. The synthetic route is as follows., Computed Properties of C9H6N2O2

To an ice cooled solution of the title compound from Step A above (5.6 g), di-tert-butyl dicarbonate (14.06 g) and NiCl2-OH2O (1.53 g) in MeOH, NaBH4 (8.51 g) was added in portions. The mixture was vigorously stirred for Ih at O0C and Ih at room temperature. After the addition of diethylenetriamine (3.5 mL) the mixture was concentrated, diluted with EtOAc, washed subsequently with IN HCl, saturated aqueous NaHCO3 and saturated aqueous NaCl, dried (MgSO4), concentrated to afford the title compound as an off-white solid (7.91 g, 88%). [M+Na]+ = 397.

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 134997-74-3.

Reference:
Patent; ALANTOS PHARMACEUTICALS HOLDING, INC.; WO2008/63667; (2008); 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. 5922-60-1, name is 2-Amino-5-chlorobenzonitrile belongs to nitriles-buliding-blocks compound, it is a common compound, a new synthetic route is introduced below. Quality Control of 2-Amino-5-chlorobenzonitrile

Step 1 Methyl 4-chloro-2-cyanophenylcarbamate A 100 mL round bottom flask was charged with 2-amino-5-chlorobenzonitrile (0.76 g, 5.0 mmol), methyl chloroformate (0.43 mL, 5.40 mmol), NaHCO3 (0.5 g, 6.0 mmol) and 2-butanone (25 mL). The resulting mixture was stirred overnight at reflux. Reaction progress was monitored by TLC (EtOAc/Petroleum ether=1:10). Work-up: the reaction mixture was filtered and the solid was washed more 2-butanone (20 mL*2). The filtrate was concentrated in vacuo, to give 0.95 g (97percent) of the product as white solid.

The synthetic route of 5922-60-1 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; Kalypsys, Inc.; Alcon Research, Ltd; US2010/120741; (2010); A1;,
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Related Products of 20249-16-5,Some common heterocyclic compound, 20249-16-5, name is 3-Oxocyclobutanecarbonitrile, molecular formula is C5H5NO, 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.

After cooling a solution of 3-oxocyclobutanecarbonitrile (32 g, 336 mmol) in methanol (330 mL) to 0 C.,NaBH4 (6.37 g, 168 mmol) was added in small portions. The mixture was stirred at 0 C. for 1 hour.The reaction mixture was quenched with saturated aqueous NaHCO 3 and extracted with ethyl acetate (800 mL).The organic layer was dried over Na2SO4, filtered,Concentrated. This procedure was repeated two more times on the same scale, combined for purification by silica gel chromatography, eluting with 10: 1 to 1: 1 petroleum ether: ethyl acetate to yield the product (30.3 g, 296 mmol, yield). 70%).

The synthetic route of 20249-16-5 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; Abbvie Incorporated; Argiriadi, Maria A.; Breinlinger, Eric C.; Chien, Ellen Yulin Tsai; Cowart, Marlon D.; Frank, Kristine E.; Friedman, Michael M.; Hardy, David J.; Herold, J. Martin; Liu, Huaqing; Chu, Wei; Scanio, Marc J.; Schrimpf, Michael R.; Vargo, Thomas R.; Van Epps, Stacy A.; Webster, Matthew P.; Little, Andrew J.; Dunstan, Teresa A.; Katcher, Matthew H.; Schedler, David A.; (232 pag.)JP6557436; (2019); B1;,
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Synthetic Route of 1187-42-4, These common heterocyclic compound, 1187-42-4, name is Diaminomaleonitrile, 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.

In a 100 mL two-necked flask, 2.6 lg (10 mmol) of 5-bromoacenaphthenequinone, 1.08 g (10 mmol) of diaminomaleonitrile, and 60 mL of acetic acid were sequentially added thereto, and the temperature was raised to 120 ¡ã C, and the mixture was stirred under reflux for 24 hours. The mixture was cooled to room temperature, poured into water, filtered under reduced pressure and washed with a large amount of water. The residue was dried and separated and purified on a silica gel column using dichloromethane: petroleum ether = 3:1 (volume ratio) eluent to obtain yellow. 3-bromoacenaphthenequinoneopyrazine-8,9-dicarbonitrile 2.44g, yield 77¡¤27percent

The synthetic route of 1187-42-4 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; Soochow University (Suzhou); Liao Liangsheng; Yuan Yi; Jiang Zuoquan; Hu Yun; (37 pag.)CN108440424; (2018); A;,
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