4-Methylmorpholine → 2-[1-(4-methanesulfonyl-phenyl)-3-methyl-butyl]-1H-pyrrolo[2,3-b]pyridin-5-carboxylic acid methylamide

Participants

Reaction Conditions

Reaction Steps

To a solution of 2-[1-(4-methanesulfonyl-phenyl)-3-methyl-butyl]-1H-pyrrolo[2,3-b]pyridin-5-carboxylic acid (prepared as in Example 1, 432 mg, 1.12 mmol) and methylamine hydrochloride (151 mg, 2.23 mmol) in dichloromethane (8 mL), N,N-dimethylformamide (2 mL) and N-methylmorpholine (370 μL, 3.36 mmol) was added 1-hydroxybenzotriazole hydrate (380 mg, 2.8 mmol) followed by N-(3-dimethylaminopropyl)-N′-ethylcarbodiimide hydrochloride (540 mg, 2.8 mmol) in one portion. The mixture was then stirred at 25° C. for 14 h. The mixture was diluted with ethyl acetate (200 mL), washed with a 1 N aqueous sodium bicarbonate solution, 1 N aqueous hydrochloric acid solution, brine, dried over anhydrous sodium sulfate and then concentrated in vacuo. Purification using a Waters automated flash system (column: Xterra 30 mm×100 mm, sample manager 2767, pump 2525, detector: ZQ mass and UV 2487, solvent system: acetonitrile and 0.1% ammonium hydroxide in water) afforded 2-[1-(4-methanesulfonyl-phenyl)-3-methyl-butyl]-1H-pyrrolo[2,3-b]pyridin-5-carboxylic acid methylamide (53 mg, 12%) as a white solid: LC/MS m/e calcd for C21H26N3O3S [M+H]+ 400.52, observed 400.2; 1H NMR (400 MHz, CDCl3) δ ppm 0.97 (d, J=6.9 Hz, 3H), 0.99 (d, J=6.9 Hz, 3H), 1.52 (m, 1H), 1.96 (m, 1H), 2.11 (m, 1H), 3.04 (s, 3H), 3.08 (d, J=4.4 Hz, 3H), 4.31 (m, 1H), 6.35 (m, 1H), 6.42 (s, 1H), 7.41 (d, J=8.3 Hz, 2H), 7.82 (d, J=8.3 Hz, 2H), 8.25 (s, 1H), 8.50 (s, 1H), 10.84 (br. s., 1H).

Provenance & Evidence