Potassium Hydroxide → HCID 178485534, compound

Participants

Reaction Conditions

Reaction Steps

A light brown solution of 2-({2-{[1-(N,N-dimethylglycyl)-5-(methoxy)-2,3-dihydro-1H-indol-6-yl]amino}-7-[(4-methylphenyl)sulfonyl]-7H-pyrrolo[2,3-d]pyrimidin-4-yl}amino)-6-fluoro-N-methylbenzamide (19.1 kg, 27.8 mol), a method for preparation of which is described in Step C above, was suspended in dioxane (191 L, 10 volumes) and treated with a 15% aqueous KOH solution (76.4 L, 4 volumes). The mixture was heated to reflux (approximately 85° C.). Once the suspension became homogeneous, the reaction mixture was kept at reflux for 2 hours. In-process monitoring after 2 h showed completion. The heat was discontinued and the suspension was concentrated to remove approximately 80 L of solvent. Water (141 L) was added and the suspension was stirred at ambient temperature for 1 h and filtered through centrifuge. The solid was washed with water till the filtrate ran clear to obtain 2-[(2-{[1-(N,N-dimethylglycyl)-5-(methyloxy)-2,3-dihydro-1H-indol-6-yl]amino}-1H-pyrrolo[2,3-d]pyrimidin-4-yl)amino]-6-fluoro-N-methylbenzamide monohydrate as a light brown solid (14.1 kg, 95% yield).

Provenance & Evidence