Trifluoroacetic acid → 4-{4-[4-Fluoro-3-(1-methylpiperidin-4-yl)-phenyl-amino]-7H-pyrrolo[2,3-d]pyrimidin-6-yl}-3,6-dihydro-2H-pyridine-1-carboxylic acid tert-butyl ester

Participants

Reaction Conditions

Reaction Steps

A mixture of 4-(4-chloro-7H-pyrrolo[2,3-d]pyrimidin-6-yl)-3,6-dihydro-2H-pyridine-1-carboxylic acid tert-butyl ester (167 mg, 0.500 mmol), 4-fluoro-3-(1-methylpiperidin-4-yl)-phenylamine (149 mg, 0.600 mmol), N,N-dimethylformamide (3 mL), and trifluoroacetic acid (385 μL, 5.18 mmol) in a sealed tube was heated at 100° C. for 15 h. The mixture was concentrated in vacuo, charged with sodium bicarbonate (504 mg, 6.00 mmol), di-tert-butyldicarbonate (120 mg, 0.550 mmol), and N,N-dimethylformamide (2 mL), and stirred at rt under N2 for 24 h. After that time, the mixture was filtered, and the filtrate was concentrated in vacuo to obtain a brown oil, which was dissolved in EtOAc (30 mL) and washed with water (3×20 mL). The organic phase was concentrated in vacuo to obtain a light-brown oil that was purified by HPLC to give the title compound. 1H NMR (CD3OD, 400 MHz): δ=1.51 (s, 9H), 1.87 (brs, 4H), 2.13-2.20 (m, 2H), 2.32 (s, 3H), 2.54 (brs, 2H), 2.83-2.91 (m, 1H), 2.99-3.01 (m, 2H), 3.65 (brs, 2H), 4.12 (brs, 2H), 6.27 (brs, 1H), 6.56 (s, 1H), 7.03 (t, 1H, J=8.8 Hz), 7.57-7.60 (m, 2H), 8.19 (s, 1H). MS (ES+): m/z 507.17 (75) [MH+]. HPLC: tR=2.16 min (ZQ2000, polar—5 min).

Provenance & Evidence