Electric Literature of 200049-46-3,Some common heterocyclic compound, 200049-46-3, name is 7-Bromo-2,3-dihydro-isoindol-1-one, molecular formula is C8H6BrNO, 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 1 -(3 -bromo- 1 -(tetrahydro-2H-pyran-4-yl)-6, 7-dihydro- 1H-pyrazolo[4, 3-c]pyridin-5(4H)-yl)ethanone (Intermediate H, 350 mg, 1.07 mmol) and bis(pinacolato)diboron(542 mg, 2.13 mmol) in dioxane (5.3 mL) was added KOAc (314 mg, 3.20 mmol), (2- dicyclohexylphosphino-2?,4?,6?-triisopropyl- 1,1 ?-biphenyl)[2-(2?-amino- 1,1?- biphenyl)]palladium(II) methanesulfonate (26 mg, 0.032 mmol) and 2-(dicyclohexylphosphino)- 2?,4?,6?-triisopropylbiphenyl (31 mg, 0.064 mmol). The mixture was stirred at 80C for 16 hunder a nitrogen atmosphere. The reaction mixture was cooled to room temperature and 7- bromoisoindolin-1-one (113 mg, 0.533 mmol), K3P04.H20 (313 mg, 1.33 mmol), water (1.3 mL) and (2-dicyclohexylphosphino-2?,4?,6?-triisopropyl- 1,1 ?-biphenyl)[2-(2?-amino- 1,1?- biphenyl)]palladium(II) methanesulfonate (26 mg, 0.032 mmol) were added. The reaction mixture was stirred at 90 C for 4 h under a nitrogen atmosphere. The reaction mixture was thencooled to room temperature and concentrated in vacuo. The crude residue was dissolved indichloromethane (20 mL), dried over anhydrous MgSO4, filtered through celite and concentrated in vacuo. The mixture obtained was purified by silica gel chromatography (MeOH / iPrOAc = 1 10 to 1: 3) to give the title compound (144 mg, 36%) as a white solid. ?H NMR (400 IVIFIz, DMSO-d6, 23 / 24 H) 7.66 – 7.40 (m, 3H), 6.06 – 5.94 (m, 1H), 4.48 (d, J = 9.5 Hz, 2H), 4.62-4.41 (m, 1H),4.18(dd,J36.7, 11.6Hz,2H),3.99-3.77(m,2H),3.59-3.47(m,3H),2.82 (dt, J = 24.3, 5.9 Hz, 2H), 2.43 -2.30 (m, 2H), 2.17-2.06 (m, 3H), 1.93 (d, J = 13.2 Hz, 2H). LCMS M/Z (M+H) 381.
These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route 7-Bromo-2,3-dihydro-isoindol-1-one, its application will become more common.
Reference:
Patent; GENENTECH, INC.; CONSTELLATION PHARMACEUTICALS, INC.; CYR, Patrick; BRONNER, Sarah; ROMERO, F. Anthony; MAGNUSON, Steven; TSUI, Vickie Hsiao-Wei; MURRAY, Jeremy M.; WAI, John; LAI, Kwong Wah; WANG, Fei; CHEN, Kevin X.; (351 pag.)WO2017/205538; (2017); A1;,
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