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

Participants

Reaction Conditions

Reaction Steps

To a solution of 2-[2-cyclopentyl-1-(4-methanesulfonyl-phenyl)-ethyl]-1H-pyrrolo[2,3-b]pyridin-5-carboxylic acid (200 mg, 0.48 mmol) and isopropylamine (50 μL, 0.62 mmol) in dichloromethane (1 mL), N,N-dimethylformamide (500 μL) and N-methylmorpholine (150 μL, 1.45 mmol) was added 1-hydroxybenzotriazole hydrate (132 mg, 0.97 mmol) followed by N-(3-dimethylaminopropyl)-N′-ethylcarbodiimide hydrochloride (186 mg, 0.97 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-[2-cyclopentyl-1-(4-methanesulfonyl-phenyl)-ethyl]-1H-pyrrolo[2,3-b]pyridin-5-carboxylic acid isopropylamide (80 mg, 36%) as a white solid: LC/MS m/e calcd for C25H31N3O3S [M+H]+ 454.61, observed 454.4; 1H NMR (400 MHz, CDCl3) δ ppm 1.12 (m, 2H), 1.24 (d, J=6.7 Hz, 6H), 1.43 (m, 2H), 1.52-1.81 (m, 5H, H), 2.04 (m, 1H), 2.17 (m, 1H), 2.99 (s, 3H), 4.18 (t, J=7.9 Hz, 1H), 4.25 (m, 1H), 6.34 (s, 1H), 6.60 (d, J=7.6 Hz, 1H), 7.41 (d, J=8.1 Hz, 2H), 7.78 (d, J=8.1 Hz, 2H), 8.23 (d, J=1.8 Hz, 1H), 8.53 (d, J=1.8 Hz, 1H), 10.72 (br, 1H).

Provenance & Evidence