Potassium Phosphate, Tribasic → (R,E)-ethyl 4-((5-fluoro-2-(5-fluoro-1-tosyl-1H-pyrrolo[2,3-b]pyridin-3-yl)pyrimidin-4-yl)amino)-5,5-dimethylhex-2-enoate

Participants

Reaction Conditions

Reaction Steps

K3PO4 (1.078 g, 5.079 mmol) was dissolved in water (3.2 mL) and added to a solution of (R,E)-ethyl 4-((2-chloro-5-fluoropyrimidin-4-yl)amino)-5,5-dimethylhex-2-enoate, 37a, (0.534 g, 1.693 mmol) in 2-methyl-THF (10.7 mL) and the mixture was purged with nitrogen for 30 minutes. 5-fluoro-1-(p-tolylsulfonyl)-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyrrolo[2,3-b]pyridine, 7a, (0.775 g, 1.862 mmol) was added and the nitrogen purging was continued for an additional 15 min. X-Phos (0.048 g, 0.102 mmol) and Pd2(dba)3 (0.031 g, 0.034 mmol) were added and the mixture was heated at 80° C. overnight. After cooling to room temperature, the reaction mixture was diluted with water and extracted with EtOAc. The layers were separated and the organic phase was washed with brine, dried over MgSO4, filtered and evaporated to dryness. The crude residue was dissolved in a minimum volume of dichloromethane and purified by silica gel chromatography (0-100% EtOAc/hexanes gradient) to afford 650 mg of desired product: 1H NMR (400 MHz, CDCl3) δ 8.57-8.38 (m, 2H), 8.30 (s, 1H), 8.11 (dd, J=10.5, 5.5 Hz, 3H), 7.08 (dt, J=36.7, 18.3 Hz, 1H), 6.01 (d, J=15.7 Hz, 1H), 5.11 (d, J=8.7 Hz, 1H), 4.97-4.77 (m, 1H), 4.19 (q, J=7.1 Hz, 2H), 2.39 (d, J=10.7 Hz, 3H), 1.27 (q, J=7.4 Hz, 4H), 1.10 (s, 9H); LCMS Gradient 10-90%, 0.1% formic acid, 5 minutes, C18/ACN, RT=3.99 minutes (M+H) 570.01.

Provenance & Evidence