Dichloromethane → (R)-2-(3-(4-amino-3-(4-(3,5-difluorophenoxy)phenyl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl)piperidine-1-carbonyl)-3-cyclopropylacrylonitrile

Into a 50 mL round-bottom flask, was placed a solution of 3-[(3R)-3-[4-amino-3-[4-(3,5-difluorophenoxy)phenyl]-1H-pyrazolo[3,4-d]pyrimidin-1-yl]piperidin-1-yl]-3-oxopropanenitrile (150 mg, 0.31 mmol, 1.00 equiv) in methanol (20 mL), cyclopropanecarbaldehyde (64 mg, 0.91 mmol, 3.00 equiv), piperidine (13 mg, 0.15 mmol, 0.50 equiv), and dichloromethane (5 mL). The resulting solution was stirred for 12 h at room temperature and then concentrated under vacuum. The residue was loaded onto a silica gel column and eluted with dichloromethane/methanol (100:1) to give 70 mg (42%) of the title compound as a white solid. LC-MS: (ES, m/z): 542 [M+H]+. 1HNMR (300 MHz, CDCl3, ppm) 8.405 (1H, s), 7.762˜7.715 (2H, m), 7.282˜7.223 (2H, m), 6.656˜6.575 (4H, m), 6.696 (2H, s), 5.022˜4.924 (1H, m), 4.8˜2.9 (4H, m), 2.424˜2.301 (2H, m), 2.271˜2.259 (3H, d), 1.295˜1.228 (2H, t), 0.903˜0.892 (2H, d).

1. customInto a 50 mL round-bottom flask, was placed
2. concentrationconcentrated under vacuum
3. washeluted with dichloromethane/methanol (100:1)

ORD record

ord-436d9e65db894bcfa7595cb2fac7dc5b

Source dataset

uspto-grants-2015_02

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08962635B2