Potassium Hydroxide → HCID 178485533, compound

Participants

Reaction Conditions

Reaction Steps

A light brown solution of 2-({2-{[1-(N,N-dimethylglycyl)-5-(methyloxy)-2,3-dihydro-1H-indol-6-yl]amino}-7-[(4-methylphenyl)sulfonyl]-7H-pyrrolo[2,3-d]pyrimidin-4-yl}amino)-6-fluoro-N-methylbenzamide (26 g, 37.9 mmol) prepared in multiple batches as described in Step C above, in dioxane (900 mL) was treated with a 1N aqueous KOH solution (379 mL, 379 mmol). The resulting mixture was heated in a 90° C. bath for 3 hours. The resulting mixture was allowed to cool to room temperature, then was diluted with EtOAc (500 mL). The organic layer was separated and sequentially washed with a 2N aqueous NaOH solution (2×200 mL) and a saturated NaCl solution (300 mL), then concentrated to a thick slurry. The resulting slurry was filtered and the solid washed with Et2O. The filtrate was concentrated to a slurry, filtered, and combined with the previous residue to obtain 2-[(2-{[1-(N,N-dimethylglycyl)-5-(methyloxy)-2,3-dihydro-1H-indol-6-yl]amino}-1H-pyrrolo[2,3-d]pyrimidin-4-yl)amino]-6-fluoro-N-methylbenzamide as a light brown solid. (16.9 g, 84%, Yield). The remaining filtrate was concentrated and purified by flash silica gel chromatography using 1-10% MeOH (0.2% NH3)/CH2Cl2 affording an additional 1 g (5%). 1H NMR (400 MHz, DMSO-d6) δ ppm 2.28 (s, 6H), 2.82 (d, J=4.40 Hz, 3H), 3.08-3.15 (m, 2H), 3.22 (s, 2H), 3.79 (s, 3H), 4.16 (t, J=8.25 Hz, 2H), 6.27 (d, J=1.83 Hz, 1H), 6.80-6.89 (m, 1H), 6.92 (d, J=2.20 Hz, 1H), 6.93 (s, 1H), 7.26-7.35 (m, 1H), 7.38 (s, 1H), 8.28 (s, 1H), 8.36 (d, J=8.43 Hz, 1H), 8.65 (s, 1H), 10.10 (s, 1H), 11.06 (s, 1H). ESIMS (M+H)=533.

Provenance & Evidence