Hydrochloric Acid → Hydrochloric Acid

Participants

Reaction Steps

A slurry of 5-(2,4-diamino-pyrimidin-5-yloxy)-4-isopropyl-2-methoxy-benzenesulfonamide sulfolane solvate (23.86 kg) in a mixture of ethanol (74.3 kg) and 0.44 N HCl (109.4 kg) was heated to reflux to provide a homogeneous solution of the monohydrochloride salt of 5-(2,4-diamino-pyrimidin-5-yloxy)-4-isopropyl-2-methoxy-benzenesulfonamide. This solution was filtered while hot, then treated with concentrated ammonium hydroxide (3.4 L) to liberate the free base of 5-(2,4-diamino-pyrimidin-5-yloxy)-4-isopropyl-2-methoxy-benzenesulfonamide. The resultant mixture was cooled slowly to 20 degrees C. and the crystalline product isolated by filtration. The filter cake was washed with water (20.1 kg) and dried under reduced pressure at 70 degrees C. to a constant weight of 8.17 kg (57.7% yield based on di-solvate of sulfolane). MP=281-282° C. 1H nmr (DMSO-d6) delta: 1.27 (d, 6H, J=6.9 Hz), 3.41 (septet, 1H, J=6.9 Hz), 3.89 (s, 3H), 5.87 (s (br), 2H), 6.40 (s (br), 2H), 6.98 (s, 1H), 7.01 (s (br), 2H), 7.07 (s, 1H), 7.36 (s, 1H).

Provenance & Evidence