Trifluoroacetic acid → HCID 178460284, compound

Participants

Reaction Steps

N-{trans-3-[(2-[(1-methyl-1H-pyrazol-4-yl)amino]-7-{[2-(trimethylsilyl)ethoxy]methyl}-7H-pyrrolo[2,3-d]pyrimidin-4-yl)amino]cyclobutyl}prop-2-enamide (18 mmol) was dissolved in DCM (5 mL) and TFA (0.5 mL) was added. After stirring for 3 hrs, the solvents were removed and chromatography eluting with a gradient of 2%-20% EtOH in DCM to afford N-[trans-3-({7-(hydroxymethyl)-2-[(1-methyl-1H-pyrazol-4-yl)amino]-7H-pyrrolo[2,3-d]pyrimidin-4-yl}amino)cyclobutyl]prop-2-enamide. To this N-hydroxymethyl intermediate, was added EtOH (5 mL) and K2CO3 (100 mg) dissolved in water (2.5 mL). The reaction was allowed to stir for 6 hrs and the solvents were removed. Water (3 mL) was added and the product was extracted into 2-methyl-THF (four×3 mL). After drying the organic extract over MgSO4, filtering, and concentrating, the white residue was carefully precipitated from DCM/MeOH/heptane (1:1:1) to afford the title compound (16 mg, 26% yield). 1H NMR (400 MHz, DMSO-d6) δ ppm 10.8 (br. s., 1H), 8.52 (d, J=6.80 Hz, 1H), 8.32 (s, 1H), 7.86 (s, 1H), 7.45 (s, 1H), 6.87 (s, 1H), 6.72 (br. s., 1H), 6.64 (s, 1H), 6.18-6.29 (m, 1H), 6.12 (d, J=1.76 Hz, 1H), 5.60 (dd, J=10.07, 2.01 Hz, 1H), 4.68 (d, J=6.29 Hz, 1H), 4.40 (d, J=6.55 Hz, 1H), 2.37 (br. s., 3H), 2.18 (s, 2H). m/z (APCI+) for C17H20N8O 353.1 (M+H)+.

Provenance & Evidence