Methanol → 7-Bromo-2-chloro-4-(4-morpholinyl)-thieno[3,2-d]pyrimidine

Reaction equation

[Br:1][C:2]1[C:6]2[N:7]=[C:8]([Cl:12])[N:9]=[C:10](Cl)[C:5]=2[S:4][CH:3]=1.CO.[NH:15]1[CH2:20][CH2:19][O:18][CH2:17][CH2:16]1>>[Br:1][C:2]1[C:6]2[N:7]=[C:8]([Cl:12])[N:9]=[C:10]([N:15]3[CH2:20][CH2:19][O:18][CH2:17][CH2:16]3)[C:5]=2[S:4][CH:3]=1

Participants

Reactant 3

HCID 887Methanol

HCID 8083Morpholine

HCID 183264227-Bromo-2,4-dichlorothieno[3,2-d]pyrimidine

Product 1

HCID 534387087-Bromo-2-chloro-4-(4-morpholinyl)-thieno[3,2-d]pyrimidineYield 35.9%

Procedure

7-Bromo-2,4-dichlorothieno[3,2-d]pyrimidine (2.9 g, 10.0 mmol) was dissolved in methanol (100 mL, 2000 mmol) and added morpholine (2 mL, 22 mmol) and let the reaction mixture stir for 1.5 h. Complete reaction confirmed by LCMS. Concentrated in vacuo and diluted with water. Extracted with DCM and concentrated in vacuo again. The product was purified by silica gel chromatography (0 to 100% ethyl acetate/heptanes) on the CombiFlash® Rf system and concentrated in vacuo to give 4-(7-bromo-2-chlorothieno[3,2-d]pyrimidin-4-yl)morpholine (1.2 g, 35% yield). 1H NMR (400 MHz, CDCl3) δ 7.78 (s, 1H), 4.01 (m, 4H), 3.85 (m, 4H)