1-{[1-(5-Allyloxy-2-tert-butoxycarbonylamino-pentanoyl)-4-(6-methoxy-isoquinolin-1-yloxy)-pyrrolidine-2-carbonyl]-amino}-2-vinyl-cyclopropanecarboxylic acid ethyl ester → 14-Tert-butoxycarbonylamino-18-(6-methoxy-isoquinolin-1-yloxy)-2,15-dioxo-10-oxa-3,16-diaza-tricyclo[14.3.0.04,6]nonadec-7-ene-4-carboxylic acid ethyl ester

Participants

Reaction Conditions

Reaction Steps

A solution of 1-{[1-(5-Allyloxy-2-tert-butoxycarbonylamino-pentanoyl)-4-(6-methoxy-isoquinolin-1-yloxy)-pyrrolidine-2-carbonyl]-amino}-2-vinyl-cyclopropanecarboxylic acid ethyl ester (the product of step 26F, 2.0 g, 2.94 mmol) in 800 ml of benzene was treated with Grubb's second generation catalyst (375 mg, 0.44 mmol). The reaction mixture was heated to 50° C., stirred under N2 for 2 h, and then concentrated in vacuo. Flash chromatography (silica gel, 25–100% ethyl acetate/hexane) and treatment with activated carbon gave 677.6 mg (˜35%) of 14-tert-butoxycarbonylamino-18-(6-methoxy-isoquinolin-1-yloxy)-2,15-dioxo-10-oxa-3,16-diaza-tricyclo[14.3.0.04,6]nonadec-7-ene-4-carboxylic acid ethyl ester as a brown collapsed foam: 1H NMR (500 MHz, METHANOL-D4) δ 1.06–1.30 (m, 12H), 1.51–2.03 (m, 6H), 2.41–2.70 (m, 3H), 3.39–3.50 (m, 1H), 3.51–3.61 (m, 1H), 3.77–3.87 (m, 1H), 3.92 (s, 3H), 4.02–4.18 (m, 3H), 4.24 (d, J=6.41 Hz, 1H), 4.36–4.48 (m, 1H), 4.55 (d, J=11.29 Hz, 1H), 4.65 (t, J=8.39 Hz, 1H), 5.55–5.72 (m, 2H), 5.85 (s, 1H), 7.08 (d, J=8.85 Hz, 1H), 7.17 (s, 1H), 7.24 (d, J=5.80 Hz, 1H), 7.89 (d, J=5.80 Hz, 1H), 8.16 (d, J=9.16 Hz, 1H). LC-MS (Method B, retention time: 1.58 min), MS m/z 653 (M++1).

Provenance & Evidence