Diisopropylethylamine → (2S,4S)-tert-butyl 4-(8-chloro-2-(4-isopropylthiazol-2-yl)-7-methoxyquinolin-4-yloxy)-2-(hex-5-enyl(methyl)carbamoyl)pyrrolidine-1-carboxylate

Participants

Reaction Conditions

Reaction Steps

Compound 133 (20.5 g) was dissolved in anhydrous DMF (48 mL) at room temperature. O-(Benzotriazol-1-yl)-N,N,N′,N′-tetramethyluronium tetrafluoroborate (1.25 eq.) was added at room temperature and the reaction mixture was stirred for 10 min. Compound 32a (1.1 eq.) was added and the reaction mixture was stirred for additional 10-15 min. After cooling to 5° C., diisopropylethylamine (3 eq.) was added. After warming to room temperature for 1 hr, the reaction mixture was diluted with ethyl acetate, washed with brine and ammonium chloride, dried over Na2SO4, and concentrated under vacuum to give crude 134 (22.09 g) as an orange foam. The crude product was crystallized from ethyl acetate and heptane to give compound 134 (20.55 g) as a white powder in 92% yield and 98% purity.

Provenance & Evidence