4-CHLORO-6-MORPHOLINO-2-PYRIMIDINYL METHYL SULFIDE synthesis

Yield: 98%

Reaction Conditions:

with N-ethyl-N,N-diisopropylamine in tetrahydrofuran at 60; for 18 h;

Steps:

21
Reference Example 21 6-Fluoro-4-(2-methanesulfonyl-6-morpholin-4-yl-pyrimidin- 4-vIMH-indole; To a stirred solution of 4,6-dichloro-2-(methylthio)pyrimidine (15.44 g; 79 mmol) and DIPEA (15 ml; 86 mmol) in THF (200 ml) at RT. was added morpholine (7.6 mL; 87 mmol) in one portion (a thick white precipitate forms within a few minutes). The reaction mixture was heated at 60°C overnight (18 h) during which time all solids dissolve. The cooled reaction mixture was poured into well-stirred water (1.5 L) and the resulting white solid was collected by filtration, washed with water and dried to afford 4-(6-chloro-2-methylsulfanyl- pyrimidin-4-yl)-morpholine as a white solid (19.03 g; 98 %).

References:

PIRAMED LIMITED;THE INSTITUTE OF CANCER RESEARCH WO2008/125839, 2008, A2 Location in patent:Page/Page column 24; 37-38