Some common heterocyclic compound, 124289-21-0, name is 3-Bromo-5-methylbenzonitrile, molecular formula is C8H6BrN, 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. COA of Formula: C8H6BrN
In a vial fitted with a stir bar was placed 3-bromo-5-methyl-benzonitrile (266 mg, 1.357 mmol), 1-(3,5-difluorophenyl)-1,2,4-triazol-3-amine (205 mg, 1.045 mmol), sodium tert-butoxide (106 mg, 1.103 mmol), and chloro(2-di-t- butylphosphino-2′,4′,6′-tri-i-propyl-1,1′-biphenyl)[2-(2- aminoethyl)phenyl]palladium(II) (t-BuXPhos Palladacycle) (30 mg, 0.04607 mmol). tert-Butanol (5 mL) was added and the vial was sealed and purged with nitrogen. The mixture was heated to 80 C overnight. The reaction was extracted with ethyl acetate and washed with water. The organics were treated with MP-TMT (ca 100 mg) and refluxed for 4 hours, to capture residual palladium. The organics were dried over sodium sulfate, filtered and concentrated under reduced pressure to give crude 3-[[1-(3,5-difluorophenyl)-1,2,4-triazol-3-yl]amino]-5-methyl-benzonitrile (0.35 g of 90% purity, 97%). A small sample of crude material was crystalized from acetonitrile to give analytically pure 3-[[1-(3,5-difluorophenyl)-1,2,4-triazol-3-yl]amino]-5-methyl-benzonitrile. MR (300 MHz, DMSO-d6) delta 9.94 (s, 1H), 9.21 (s, 1H), 7.84 (s, 1H), 7.76 – 7.52 (m, 3H), 7.38 – 7.20 (m, 1H), 7.15 (s, 1H), 2.35 (s, 3H) ppm. ESI- MS m/z calc. 31 1.09827, found 312.15 (M+l)+; Retention time: 0.95 minutes
These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route 124289-21-0, its application will become more common.
Reference:
Patent; VERTEX PHARMACEUTICALS INCORPORATED; BETHIEL, Randy Scott; CAO, Jingrong; COLLIER, Philip, N.; DAVIES, Robert J.; DOYLE, Elisabeth; FRANTZ, James Daniel; GOLDMAN, Brian Anthony; GREY, Ronald Lee; GRILLOT, Anne-laure; GU, Wenxin; KOLPAK, Adrianne Lynne; KRAUSS, Paul Eduardo; LIAO, Yusheng; MAGAVI, Sanjay Shivayogi; MESSERSMITH, David; PEROLA, Emanuele; RYU, Elizabeth, Jin-Sun; SYKEN, Joshua; WANG, Jian; (491 pag.)WO2018/106646; (2018); A1;,
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