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

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 (200 mg, 0.52 mmol) and isopropylamine (54 μL, 0.62 mmol) in dichloromethane (1 mL), N,N-dimethylformamide (500 μL) and N-methylmorpholine (200 μL, 1.56 mmol) was added 1-hydroxybenzotriazole hydrate (141 mg, 1.04 mmol) followed by N-(3-dimethylaminopropyl)-N′-ethylcarbodiimide hydrochloride (199 mg, 1.04 mmol) in one portion. The mixture was then stirred at 25° C. for 14 h. The mixture was diluted with ethyl acetate (100 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 isopropylamide (45 mg, 20%) as a white solid: LC/MS m/e calcd for C23H29N3O3S [M+H]+ 428.57, observed 428.2; 1H NMR (400 MHz, CDCl3) δ ppm 0.94 (d, J=6.7 Hz, 3H), 0.97 (d, J=6.7 Hz, 3H), 1.29 (d, J=6.6 Hz, 6H), 1.49 (m, 1H), 1.96 (m, 1H), 2.08 (m, 1H), 3.03 (s, 3H), 4.24-4.37 (m, 2H), 6.17 (d, J=7.9 Hz, 1H), 6.38 (s, 1H), 7.43 (d, J=8.3 Hz, 2H), 7.84 (d, J=8.3 Hz, 2H), 8.24 (d, J=2.0 Hz, 1H), 8.55 (d, J=2.0 Hz, 1H), 10.31 (br, 0.3H).

Provenance & Evidence