(6-CHLORO-2-TRIFLUOROMETHYLPYRIMIDIN-4-YL)DIMETHYL-AMINE synthesis

Yield:-

Reaction Conditions:

with N-ethyl-N,N-diisopropylamine in tetrahydrofuran at 20; for 60 h;

Steps:

47.B

To a suspension of 2-trifluoromethyl-pyrimidine-4, 6-diol (3.25 g) in POC13 (7.89 mL) was added Et3N (5.00 mL). The mixture was stirred at 120°C for 3 hr, cooled to ambient temperature, and poured into ice water. The aqueous layer was extracted with CHC13 (three times). The combined organic layer was dried over MgS04, filtrated, and concentrated under reduced pressure to give 4, 6-dichloro-2-trifluoromethyl-pyrimidine. To the solution of the above material (1.00 g) in THF (10 mL) were added iPrzNEt (0.98 mL) and 50% aqueous Me2NH (0.48 mL). The mixture was stirred at ambient temperature for 60 hr. To the solution was added saturated aqueous NaHCO3 and the aqueous layer was extracted with CHCI3 (three times). The combined organic layer was dried over MgSO4, filtered, concentrated under reduced pressure, and purified by medium-pressure liquid chromatography (silica gel, 5% to 25% EtOAc in hexane) to give (6-chloro-2- trifluoromethyl-pyrimidin-4-yl)-dimethyl-amine (728 mg). ESI MS m/e 225 M+ ; 1H NMR (300 MHz, CDC13) 8 2.77-3. 61 (m, 6 H), 6.50 (s, 1 H).

References:

WO2005/95357,2005,A2 Location in patent:Page/Page column 140; 141