Pyridine → 2-({5-[3-(Dimethylamino)propyl]-2-methylpyridin-3-yl}amino)-9-(trifluoromethyl)-5,7-dihydro-6H-pyrimido[5,4-d][1]benzazepine-6-thione

Participants

Reaction Conditions

Reaction Steps

A mixture of 2-({5-[3-(dimethylamino)propyl]-2-methylpyridin-3-yl}amino)-9-(trifluoromethyl)-5,7-dihydro-6H-pyrimido[5,4-d][1]benzazepin-6-one (175 g, 372 mmol), phosphorus pentasulfide (82.7 g, 372 mmol) and pyridine (1.35 L) was heated at 50° C. for 18 hours. HPLC analysis showed completion of the reaction. After the reaction mixture was cooled below room temperature, a solution of sodium carbonate (525 g, 4.95 mol) in 5.1 L of water was slowly added while the temperature was kept at below room temperature. The resulting biphasic solution was separated and the organic layer was washed with the same amount of sodium carbonate solution two times. The organic phase was then reduced to ca. 1.1 L in volume. The solution was diluted with water (1.0 L) and stirred at room temperature overnight resulting in a yellow suspension. The solid was filtered and washed with 200 mL EtOH/water (1 vol/2vol), and water 200 mL. After drying overnight under vacuo at 40° C., the crude product was dissolved in 1.2 L of EtOH at reflux. Water (2.0 L) was slowly added at 75° C. to induce crystallization. The suspension was then slowly cooled to room temperature and stirred overnight. The solid 2-({5-[3-(Dimethylamino)propyl]-2-methylpyridin-3-yl}amino)-9-(trifluoromethyl)-5,7-dihydro-6H-pyrimido[5,4-d][1]benzazepine-6-thione was filtered and dried under vac at 40° C. to a constant weight (140.0 g, HPLC purity >98%, 77% yield). LCMS (FA): Rt=6.26 min, m/z=485.2 (M−H).

Provenance & Evidence