1,4-Dioxane → (2S,4S)-4-{4-[6-amino-5-(5-chloro-8-fluoroisoquinolin-3-yl)-pyridin-3-yl]-pyrazol-1-yl}-pyrrolidine-2-carboxylic acid

Participants

Reaction Conditions

Reaction Steps

A mixture of 3-(5-chloro-8-fluoroisoquinolin-3-yl)-5-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-pyridin-2-ylamine (100 mg, 0.250 mmol), (2S,4S)-4-(4-iodopyrazol-1-yl)-pyrrolidine-1,2-dicarboxylic acid 1-benzyl ester 2-methyl ester (137.0 mg, 0.300 mmol), Pd(PPh3)4 (29 mg, 0.025 mmol), potassium fluoride (43.6 mg, 0.751 mmol) and 4:1 dioxane:water (3 mL) was heated in the microwave reactor to 85° C. for 30 min. The material was concentrated in vacuo, then dry-loaded onto silica gel for column chromatography. The product was eluted with 2→5% MeOH/DCM, and the fractions containing the product were concentrated in vacuo. The material was dissolved in conc. HCl, transferred to a sealed tube and heated at 60° C. for 2 h. The solvent was removed in vacuo to afford the title compound as a brown solid. MS (ES+): m/z=453.09/455.10 (100/37) [MH+]. HPLC: tR=1.94 min (ZQ2, polar—5 min).

Provenance & Evidence