Methanol → Trametinib

Participants

Reaction Steps

Under a nitrogen atmosphere, tetrahydrofuran (40 mL) was added to N-{3-[3-cyclopropyl-1-(2-fluoro-4-iodo-phenyl)-6,8-dimethyl-2,4,7-trioxo-1,2,3,4,7,8-hexahydro-pyrido[2,3-d]pyrimidin-5-ylamino]-phenyl}-acetamide (5 g) and a methanol solution (1.57 g) containing 28% sodium methoxide was added and the mixture was stirred at room temperature for 4 hours. Acetic acid (0.56 mL) was added to the mixture and the mixture was stirred at room temperature for 30 min. And then water (40 mL) was added and the mixture was further stirred for 1 hour. The crystals were collected by filtration and dried under reduced pressure at 40° C. to give trametinib (4.75 g). Its HPLC content of A impurity is 0.42 wt %.

Provenance & Evidence