2-(chloromethyl)-6-methylthieno[2,3-d]pyrimidin-4(3H)-one(SALTDATA: FREE) synthesis

Yield:878699-59-3 86%

Reaction Conditions:

with hydrogenchloride in 1,4-dioxane at 20; for 6 h;

Steps:

4.1.2. Preparation of 2-(chloromethyl)-6-methylthieno[2,3-d]pyrimidin-4(3H)-one (intermediate 2)

A solution of ethyl 2-amino-5-methylthiophene-3-carboxylate (1) (32.4 g, 175 mmol) and chloroacetonitrile (15.8 g, 210 mmol)in 1,4-dioxane (300 mL) was stirred at room temperature for 6 h,while hydrogen chloride gas was simultaneously passed throughthe solution. The resulting solid was collected by ltration andwashed with 1,4-dioxane. The solid was suspended in water(50 mL) and the mixture was adjusted with 25% aqueousammonia to pH 7. After stirring for 2 h, the precipitate wascollected by ltration and air-dried, and puried by re-crystallization from 1,4-dioxane to give intermediate 2 as awhite solid (32.3 g, 86%), mp 211e215C.1H NMR (600 MHz,DMSO-d6) d: 2.52 (d, J 1.2 Hz, 3H, CH3), 4.56 (s, 2H, ClCH2), 7.11(d, J 1.2 Hz, 1H, thieno[2,3-d]pyrimidine 5-H), 12.74 (s, 1H, NH).ESI-HRMS m/z: calcd for C8H8ClN2OS ([MH]): 215.0046;found:215.0042.

References:

Yang, Chao-Rui;Peng, Bin;Cao, Sheng-Li;Ren, Ting-Ting;Jiang, Wei;Wang, Fu-Cheng;Li, You-Shan;Wang, Guo;Li, Zheng;Xu, Shibin;Liao, Ji;Wang, Hailong;Li, Jing;Xu, Xingzhi [European Journal of Medicinal Chemistry,2018,vol. 154,p. 324 - 340]