Hydrochloric Acid → HCID 59441879, compound

Participants

Reaction Conditions

Reaction Steps

A slurry of 1-acetyl-5-(methyloxy)-2,3-dihydro-1H-indol-6-amine (212 mg, 2 mmol), 2-({2-chloro-7-[(4-methylphenyl)sulfonyl]-7H-pyrrolo[2,3-d]pyrimidin-4-yl}amino)-6-fluorobenzamide (836 mg, 1.8 mmol), KI (5.6 mg, 0.03 mmol) in 2,2,2-trifluoroethanol (10 mL) was treated with a 4 N HCl solution in dioxane (1.8 mL, 7.2 mmol). The reaction mixture was heated at 80° C. overnight in a sealed vessel, then was allowed to cool to rt Half of the reaction mixture was diluted with THF (100 mL) and a 27% aqueous NH4OH solution (100 mL). After stirring at rt overnight the reaction mixture was concentrated to dryness. The residue was sonicated in CH2Cl2 (10 mL), then filtered. The filtrate was purified by silica gel chromatography using 8-10% THF/CH2Cl2 to obtain 2-({2-{[1-acetyl-5-(methyloxy)-2,3-dihydro-1H-indol-6-yl]amino}-7-[(4-methylphenyl)sulfonyl]-7H-pyrrolo[2,3-d]pyrimidin-4-yl}amino)-6-fluorobenzamide as a yellow solid (192 mg, 34% for 2 steps). 1H NMR (400 MHz, DMSO-d6) δ ppm 2.16 (s, 3H), 2.35 (s, 3H), 3.19 (t, J=8.33 Hz, 2H), 3.73 (s, 3H), 4.15 (t, J=8.33 Hz, 2H), 6.50 (d, J=3.85 Hz, 1H), 6.92 (t, J=9.25 Hz, 1H), 7.04 (s, 1H), 7.15-7.40 (m, 4H), 7.90-7.99 (m, 3H), 8.02 (s, 1H), 8.10 (d, J=8.61 Hz, 1H), 8.16 (s, 1H), 8.24 (s, 1H), 10.49 (s, 1H); ESIMS (M+H)+=630.13.

Provenance & Evidence