Formic Acid → Trifluoroacetic acid

Participants

Reaction Steps

Diethyl (4-{[4-{[2-methyl-3-oxo-7-(1,2,3,6-tetrahydropyridin-4-yl)-2,3-dihydro-1H-isoindol-4-yl]amino}-5-(trifluoromethyl)pyrimidin-2-yl]amino}benzyl)phosphonate (Example 246, 20.0 mg, 0.0317 mmol), formic acid (5 uL, 0.1 mmol) and formaldehyde (3.0 uL, 0.11 mmol) were mixed in methanol (1.0 mL) at room temperature for 30 minutes. Sodium cyanoborohydride (20.0 mg, 0.318 mmol) was added and the mixture was stirred at room temperature overnight. The crude mixture was purified by MDP to obtain the title compound as a trifluoroacetic acid salt (7.3 mg, 35.7% yield). 1H NMR (400 MHz, methanol-d4) δ=1.27 (t, J=7.1 Hz, 6 H), 2.87 (br. s., 1 H), 2.93 (br. s., 1 H), 3.05 (s, 3 H), 3.19 (s, 3 H), 3.29 (d, J=21.5 Hz, 2 H), 3.36-3.46 (m, 1 H), 3.73 (br. s., 1 H), 3.80-3.90 (m, 1 H), 4.00-4.16 (m, 5 H), 4.59 (s, 2 H), 5.95-6.04 (m, 1 H), 7.34 (dd, J=8.6, 2.5 Hz, 2 H), 7.50 (d, J=8.6 Hz, 1 H), 7.58 (d, J=8.1 Hz, 2 H), 8.36-8.43 (m, 1 H), 8.75 (br. s., 1 H). MS (ES+): m/z 645.23 (100) [MH+]; HPLC: tR=0.69 min (UPLC, purity).

Provenance & Evidence