Synthetic Route of 1254319-51-1,Some common heterocyclic compound, 1254319-51-1, name is 6-Bromo-2-methylisoindolin-1-one, molecular formula is C9H8BrNO, 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.
Potassium acetate (294 mg, 3.00 mmol), bis(pinacolato)diboron (305 mg, 1.200 mmol), 6-bromo-2- methylisoindolin-l-one (271 mg, 1.200 mmol) and 2nd Generation XPHOS precatalyst (59.0 mg, 0.075 mmol) were added to a 8 mL reaction vial equipped with a stir bar. The vial was evacuated and charged 3x with nitrogen. 1,4-Dioxane (8 mL) was added, the vial was again evacuated and charged (3x) with nitrogen, and the borylation reaction was heated to 100C. Monitored by LCMS; once borylation was complete the reaction was cooled to room temperature and 2-chloro-3 -(-(( 1- fluorocyclopentyl)methyl)-lH-pyrazol-4-yl)-6-methylpyridine (INTERMEDIATE F7; 294 mg, 1.0 mmol) and l, -bis(di-tert-butylphosphino)ferrocene palladium dichloride (48.9 mg, 0.075 mmol) were added to the reaction. The vial was evacuated and charged 3x with nitrogen, then added 3M aqueous K2C03 (1.0 mL, 3.00 mmol). The reaction was then heated to 70C overnight. LCMS shows reaction is substantially complete. Cooled to room temperature, then partitioned between water and ethyl acetate. The organic was filtered over a bed of sodium sulfate. The aqueous was extracted twice more with ethyl acetate, and the organic from those extractions was used to wash the sodium sulfate as well. The combined filtrate was evaporated and taken up again in DCM, then purified by silica gel chromatography, eluting with 20-100% 3 : 1 EtOAc:EtOH in hexanes. The major peak was isolated and the volatiles were evaporated. The solid was scraped to a small particle size and treated with diethyl ether. The suspension was filtered and the solid was collected as the title compound. MS: 405 (M+l). 1H NMR (500 MHz, CDC13): delta 7.89 (s, 1H), 7.67 (d, J=7.5 Hz, 1H), 7.58 (d, J=7.7 Hz, 1H), 7.39 (d, J=7.7 Hz, 1H), 7.21 (s, 1H), 7.18 (d, J=7.8 Hz, 1H), 7.04(s, 1H), 4.39 (s, 2H), 4.23 (d, J=21.6 Hz, 2H), 3.20 (s, 3H), 2.62 (s, 3H), 1-77-1.58 (m, 8H).
The synthetic route of 1254319-51-1 has been constantly updated, and we look forward to future research findings.
Reference:
Patent; MERCK SHARP & DOHME CORP.; MSD R&D (CHINA) CO., LTD.; ACTON, John, J., III; BAO, Jianming; DENG, Qiaolin; EGBERTSON, Melissa; FERGUSON, Ronald, III; GAO, Xiaolei; HARRISON, Scott Timothy; KNOWLES, Sandra, L.; LI, Chunsing; LO, Michael Man-Chu; MAZZOLA, Robert, D., Jr.; MENG, Zhaoyang; NA, Meng; RUDD, Michael, T.; SELYUTIN, Oleg, B.; TELLERS, David, M.; TONG, Ling; ZHANG, Fengqi; (195 pag.)WO2019/5587; (2019); A1;,
Indoline – Wikipedia,
Indoline | C8H9N – PubChem