Cyclobutanol → (R)-1-(4-Fluorophenyl)-6-(6-morpholin-4-yl-pyridine-3-sulfonyl]-1,4,5,6,7,8-hexahydro-1,2,6-triaza-cyclopenta[b]naphthalene-4a-carboxylic acid cyclobutyl ester

Participants

Reaction Steps

(R)-1-(4-Fluorophenyl)-6-(6-morpholin-4-yl-pyridine-3-sulfonyl]-1,4,5,6,7,8-hexahydro-1,2,6-triaza-cyclopenta[b]naphthalene-4a-carbonyl chloride (0.12 g), triethylamine (0.11 g) and cyclobutanol (0.24 g) were heated in a microwave apparatus at 110° C. for 3 hours. The reaction mixture was concentrated under reduced pressure and the residue purified by column chromatography on silica gel, eluting with ethyl acetate in dichloromethane (1:4 to 2:3 by volume) followed by preparative reverse-phase HPLC eluting with a mixture of acetonitrile and water containing 0.1% formic acid (1:1 to 4:1 by volume) to give the title compound as a white solid (0.023 g). 1H NMR (400 MHz, CHCl3-d): δ 8.53 (d, 1H), 7.78 (dd, 1H), 7.47-7.35 (m, 3H), 7.19-7.11 (m, 2H), 6.62 (d, 1H), 6.40 (d, 1H), 4.95 (t, 1H), 4.38 (dd, 1H), 3.81 (t, 5H), 3.66 (t, 4H), 3.29 (d, 1H), 2.99-2.90 (m, 1H), 2.57 (d, 1H), 2.48-2.28 (m, 5H), 2.16-2.05 (m, 2H), 1.87-1.77 (m, 1H),1.66-1.52 (m, 1H).

Provenance & Evidence