反应详情

温度

90 °C

A mixture of 6-bromo-4-(((3aS,4R,5R,6aS)-2-(2-hydroxy-2-methylpropanoyl)-4-methyloctahydrocyclopenta[c]pyrrol-5-yl)amino)pyrrolo[1,2-b]pyridazine-3-carboxamide (32 mg, 0.055 mmol), N-methyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)picolinamide (29.0 mg, 0.111 mmol) and 2.0 M aqueous K3PO4 (0.111 mL, 0.221 mmol) in dimethylformamide (1 mL) was heated to 90° C. under nitrogen for 1 h. The crude material was purified via preparative LC/MS with the following conditions: Column: Waters XBridge C18, 19×250 mm, 5-μm particles; Guard Column: Waters XBridge C18, 19×10 mm, 5-μm particles; Mobile Phase A: 5:95 acetonitrile:water with 10-mM ammonium acetate; Mobile Phase B: 95:5 acetonitrile:water with 10-mM ammonium acetate; Gradient: 0-100% B over 25 minutes, then a 5-minute hold at 100% B; Flow: 20 mL/min. Fractions containing the desired product were combined and dried via centrifugal evaporation to give the title compound (14.9 mg, 52% yield). 1H NMR (500 MHz, 1:1 mixture of methanol-d4/chloroform-d) d 8.93 (d, J=2.0 Hz, 1H), 8.28-8.08 (m, 3H), 8.04 (d, J=1.5 Hz, 1H), 7.28 (d, J=1.5 Hz, 1H), 4.45-4.19 (m, 2H), 4.03-3.91 (m, 1H), 3.77-3.56 (m, 2H), 3.10-2.99 (m, 3H), 2.96-2.79 (m, 2H), 2.53-2.32 (m, 1H), 1.87-1.75 (m, 1H), 1.66-1.54 (m, 1H), 1.51-1.35 (m, 6H), 1.22 (d, J=6.4 Hz, 3H); MS (ES+) m/z: 520.2 (M+H); LC retention time: 1.135 min (analytical HPLC Method I).

1. customThe crude material was purified via preparative LC/MS with the following conditions
2. customa 5-minute hold
3. additionFractions containing the desired product
4. customdried via centrifugal evaporation