Trifluoroacetic acid → HCID 22346919, compound

Participants

Reaction Conditions

Reaction Steps

Oxalyl chloride (0.06 mL, 0.60 mmol) was added into a solution of indole-2-carboxylic acid (0.88 g, 0.546 mmol) in dichloromethane (5 mL) and tetrahydrofuran (5 mL) at 0° C. N,N-dimethylforamide (3 drops from 0.1 mL syringe) was added and the mixture was stirred at 0° C. for 10 minutes and at ambient temperature for 20 minutes. The solvents and excess of reagents were evaporated under reduced pressure. The residue was taken into dichloromethane (2 mL) and the resulting solution (1.25 mL) was added into a solution of tert-butyl 4-[4-amino-3-(4-amino-3-methoxyphenyl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl]-1-piperidinecarboxylate (0.12 g, 0.27 mmol) and pyridine (0.4 mL) in dichloromethane (1 mL). The mixture was stirred at ambient temperature for 2 hours. Trifluoroacetic acid (1 mL) was added and the mixture was stirred at ambient temperature for 2 hours. The solvents were evaporated under reduced pressure and the residue was purified by preparative HPLC to yield 4-(4-amino-3-{4-[(1H-2-indolylcarbonyl)amino]-3-methoxyphenyl}-1H-pyrazolo[3,4-d]pyrimidin-1-yl)hexahydropyridinium acetate (0.07 g, 0.14 mmol) as a white solid: 1H NMR (DMSO-d6, 400 MHz) δ 11.85 (br, 1H), 9.45 (s, 1H), 8.24 (d, 1H), 8.12 (d, 1H), 7.68(d, 1H), 7.48 (d, 1H), 7.40 (s, 1H), 7.35 (s, 1H), 7.30 (d, 1H), 7.24 (t, 1H), 7.09 (t, 1H), 4.77 (mn, 1H), 3.97 (s, 3H), 3.11 (mn, 2H), 2.68 (m, 2H), 2.09 (m, 2H), 1.89 (s, 3H), 1.84 (mn, 2H); MS: MH+ 483.

Provenance & Evidence