Hydroxylamine → (3-{4-[3-(4-aminophenyl)-1-ethyl-1H-pyrazol-4-yl]-1H-pyrrolo[2,3-b]pyridin-2-yl}phenyl)methanol

Participants

Reaction Steps

To {3-[4-[1-ethyl-3-(4-nitrophenyl)-1H-pyrazol-4-yl]-1-(phenylsulfonyl)-1H-pyrrolo[2,3-b]pyridin-2-yl]phenyl}methanol (26.90 g, 46.4 mMol) in MeOH (400 mL) was added 20% Pd(OH)2/C (Pearlman's catalyst) (˜3.0 g). Two balloons of H2 were attached and the reaction stirred overnight at RT. (LCMS of the reaction mixture showed 31% of the desired aniline (M+H)+=550.3, 50% of the hydroxylamine intermediate (M+H)+=566.2 and 20% of the starting material and nitroso intermediate (M+H)+=580.4 and 564.1.) Another 3.0 g of the Pearlman's catalyst was added and the reaction stirred under H2 for an additional 24 h. (LCMS showed that the reaction had gone to >90% complete. The same reaction was later shown to go to completion, under 50 psi H2, in the Parr reactor overnight at RT.) The reaction was filtered through a pad of Celite®, rinsed with MeOH and concentrated under vacuum. The remaining residue was taken up in MeOH (300 mL) and treated with aq. 6 N NaOH (25 mL, 150 mMol). The reaction was stirred and heated at 70° C. for 8 h, cooled to RT and concentrated to near dryness under vacuum. The slurry was triturated with cold water, filtered, washed with cold water, and dried under vacuum. Purification by flash chromatography on silica gel (5 to 15% MeOH/CHCl3) (product slow to dissolve on the column) gave the title compound (16.19 g, 85%) as a yellow solid: MS (ES) m/e 410.4 (M+H)+; 1H NMR (400 MHz, DMSO-d6) 12.11 (d, J=1.8 Hz, 1H), 8.21 (s, 1H), 8.05 (d, J=5.1 Hz, 1H), 7.84 (s, 1H), 7.78 (d, J=7.8 Hz, 1H), 7.41 (t, J=7.7 Hz, 1H), 7.31 (d, J=7.6 Hz, 1H), 7.08 (d, J=8.6 Hz, 2H), 6.81 (d, J=2.3 Hz, 1H), 6.80 (d, J=5.1 Hz, 1H), 6.49 (d, J=8.6 Hz, 2H), 5.27 (t, J=5.8 Hz, 1H), 5.14 (s, 2H), 4.56 (d, J=5.8 Hz, 2H), 4.24 (q, J=7.2 Hz, 2H), 1.49 (t, J=7.3 Hz, 3H).

Provenance & Evidence