Potassium Phosphate, Tribasic → tert-Butyl 3-carbamoyl-2-(3-chloro-4-fluorophenyl)-6-cyclopropyl-6,7-dihydropyrazolo[1,5-a]pyrazine-5(4H)-carboxylate

Participants

Reaction Conditions

Reaction Steps

To a stirred suspension of Intermediate 348G (0.47 g, 1.087 mmol) in 1,4-dioxane (5 mL) was added K3PO4 (1.631 mL, 3.26 mmol), (3-chloro-4-fluorophenyl)boronic acid (0.246 g, 1.414 mmol) and the reaction mixture was purged with nitrogen for 10 min. PdCl2(dppf)-CH2Cl2 (0.053 g, 0.065 mmol) was then added and the reaction mixture was heated to 80° C. and stirred for 6 h. The reaction mixture was filtered through CELITE® and the filtrate was diluted with ethyl acetate (10 mL), and washed with water and brine. The organic layer was dried over Na2SO4, filtered and the filtrate concentrated under reduced pressure. The crude compound was purified by silica gel chromatography (12 g REDISEP® column, eluting with 2% MeOH in CHCl3). Fractions containing the product were combined and evaporated to afford Intermediate 348H as an off-white solid (0.4 g, 85%). MS(ES): m/z=435 [M+H]+; 1H NMR (300 MHz, DMSO-d6) δ ppm 7.85-7.95 (m, 1H), 7.66-7.77 (m, 1H), 7.47 (t, J=9.07 Hz, 1H), 7.20-7.39 (m, 2H), 5.05 (d, J=17.37 Hz, 1H), 4.55 (d, J=17.37 Hz, 1H), 4.24 (br. s., 2H), 3.89 (br. s., 1H), 1.45 (s, 9H), 0.87-1.05 (m, 1H), 0.31-0.55 (m, 4H).

Provenance & Evidence