Reference of 7251-09-4, A common heterocyclic compound, 7251-09-4, name is 4-Amino-2-methoxybenzonitrile, molecular formula is C8H8N2O, 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.
A mixture of 3-acetyl-6-chloroquinolin-2(lH)-one (39.4 mg, 0.178 mmol) and 4-amino-2-methoxybenzonitrile (27.2 mg, 0.184 mmol) was placed under nitrogen in a dram vial. Dichloromethane (1.0 ml) was added and the suspension was stirred 10 minutes. Triisopropoxytitanium(IV) chloride (0.09 mL, 0.377 mmol) was added and the suspension was stirred overnight. Sodium triacetoxyborohydride (148.3 mg, 0.700 mmol) was added and the mixture was stirred one day. The sample was diluted with several mL MeOH, treated with silica gel, and evaporated under reduced pressure. The sample was chromatographed by Biotage MPLC with 0 to 20% MeOH in DCM, with isocratic elution at 13% MeOH. The material thus obtained was readsorbed onto silica gel and rechromatographed (10 g silica gel column) with 0 to 80% EtOAc in hexanes, with isocratic elution at 50% EtOAc to provide 4- (l-(6-chloro-2-oxo-l,2-dihydroquinolin-3-yl)ethylamino)-2-methoxybenzonitrile, 1-1 as a racemic mixture (20.3 mg, 0.053 mmol, 29.6 % yield, HPLC purity 91.63% at UV220). 1H NMR (300MHz, DMSO-d6): delta = 12.05 (s, 1H), 7.80 – 7.69 (m, 2H), 7.50 (d, J=8.8 Hz, 1H), 7.36 – 7.15 (m, 3H), 6.27 (s, 1H), 6.06 (d, J=7.6 Hz, 1H), 4.82 – 4.66 (m, J=6.4, 6.4 Hz, 1H), 3.75 (s, 3H), 1.44 (d, J=6.4 Hz, 3H). LCMS (Method 1): Rt 2.37 min., m/z 353.92 [M+H]+.
The synthetic route of 7251-09-4 has been constantly updated, and we look forward to future research findings.
Reference:
Patent; FORMA THERAPEUTICS, INC.; ASHWELL, Susan; CAMPBELL, Ann-Marie; CARAVELLA, Justin Andrew; DIEBOLD, R. Bruce; ERICSSON, Anna; GUSTAFSON, Gary; LANCIA, David R.; LIN, Jian; LU, Wei; WANG, Zhongguo; (141 pag.)WO2016/44782; (2016); A1;,
Nitrile – Wikipedia,
Nitriles – Chemistry LibreTexts