Lithium Hexamethyldisilazide → HCID 66779815, compound

Participants

Reaction Steps

A solution of 5-cyclopropyl-2-(4-morpholinyl)[1,3]thiazolo[4,5-d]pyrimidin-7(4H)-one (50 mg, 0.180 mmol) in Tetrahydrofuran (THF) (1000 μl) was stirred at 0° C. for 15 min, then lithium bis(trimethylsilyl)amide (359 μl, 0.359 mmol) in THF was added and stirring was continued for 30 min. 1-(bromomethyl)-2-methyl-3-(trifluoromethyl)benzene (54.6 mg, 0.216 mmol) in Tetrahydrofuran (THF) (300 μl) was added and the mixture was stirred at 65° C. overnight. The reaction mixture was concentrated and the residue purified by reversed-phase HPLC to provide the major regio-isomer, 5-cyclopropyl-4-{[2-methyl-3-(trifluoromethyl)phenyl]methyl}-2-(4-morpholinyl)[1,3]thiazolo[4,5-d]pyrimidin-7(4H)-one (Example 70). (9 mg, 11%); LC/MS: MS (ES+) m/e 451 (MH+); 1H NMR (400 MHz, DMSO-d6) δ ppm 0.83-0.92 (m, 2H), 0.98-1.07 (m, 2H), 1.86-1.97 (m, 1H), 2.51 (s, 3H), 3.45-3.56 (m, 4H), 3.63-3.73 (m, 4H), 5.76 (s, 2H), 6.92 (d, J=7.83 Hz, 1H), 7.37 (m, 1H), 7.64 (d, J=7.8 Hz, 1H).

Provenance & Evidence