(4-CHLORO-2-METHYLSULFANYL-PYRIMIDIN-5-YL)-METHANOL synthesis

Yield: 87.9%

Reaction Conditions:

with diisobutylaluminium hydride in tetrahydrofuran at -78; for 0.75 h;Inert atmosphere;

Steps:

(4-chloro-2-(methylthio)pyrimidin-5-yl)methanol (8i)
A mixture of ethyl 4-chloro-2-(methylthio)pyrimidine-5-carboxylate (10 g, 1.0 eq) was dissolved in THF (100 mL) to give a yellow solution. The mixture was cooled in a -78°C bath under nitrogen atmosphere. DIBAL-H (1.5 M in THF. 86 mL, 3.0 eq) was added over 45 min. via syringe. The reaction was quenched by slow addition of saturated aqueous ammonium chloride (50 mL). The mixture was then warmed to room temperature. Ethyl acetate (100 mL) and saturated aqueous sodium potassium tartrate (200 mL) were added. The mixture was stirred vigorously for 30 min. After separation of the layers, the aqueous layer was extracted with ether and the combined organics washed with brine, dried with sodium sulfate, filtered and concentrated under vacuum to give (4-chloro-2-(methylthio)pyrimidin-5-yl)methanol as a yellow solid (7.2 g, 87.9%). 1H NMR (400 MHz, DMSO-d 6 ) δ 8.63 (s, 1H), 5.56 (t, J = 5.6 Hz, 1H), 4.52 (dd, J = 5.5, 0.6 Hz, 2H), 2.54 (s, 3H). LRMS (ESI) for C 6 H 8 ClN 2 OS [M + H]+, calcd: 191.9. Found: 191.8.

References:

Hu, Xianglong;Xun, Qiuju;Zhang, Tao;Zhu, Su-Jie;Li, Qian;Tong, Linjiang;Lai, Mengzhen;Huang, Tao;Yun, Cai-Hong;Xie, Hua;Ding, Ke;Lu, Xiaoyun [Chinese Chemical Letters,2020,vol. 31,# 5,p. 1281 - 1287] Location in patent:supporting information