Piperidine → (R)-2-(2-((4-amino-3-(4-(2,6-difluorophenoxy)phenyl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl)methyl)pyrrolidine-1-carbonyl)-3-cyclopropylacrylonitrile

Participants

Reaction Conditions

Reaction Steps

Into a 10 mL sealed tube, was placed a solution of 3-[(2R)-2-([4-amino-3-[4-(2,6-difluorophenoxy)phenyl]-1H-pyrazolo[3,4-d]pyrimidin-1-yl]methyl)pyrrolidin-1-yl]-3-oxopropanenitrile (100 mg, 0.20 mmol, 1.00 equiv) in methanol (3 mL), cyclopropanecarbaldehyde (1 mL), and piperidine (1 mL). The resulting solution was stirred for 12 h at 25° C. and then concentrated under vacuum. The resulting solution was diluted with 10 mL of dichloromethane, washed with saturated aqueous NH4Cl, water and brine. The organics were dried over anhydrous sodium sulfate and concentrated under vacuum and the residue was purified via column chromatography using dichloromethane/methanol (20/1) to give 26 mg (23%) of the title compound as a white solid. LC-MS: (ES, m/z): 542 [M+H]. H-NMR: (CDCl3, ppm): δ8.38 (s, 1H); δ7.66 (d,2H); δ7.26 (d,1H); δ7.11 (d,4H); δ6.77 (d,1H); δ5.51 (s,2H); δ4.81 (m, 1H); δ4.65 (d,2H); δ3.51˜δ3.70 (m,2H); δ1.91˜δ2.01 (m,4H); δ1.81 (m, 1H); δ0.83˜1.25 (m, 4H).

Provenance & Evidence