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

HRID 346954

Reaktionsgleichung

Reaktionsgleichung von HRID 346954
[CH2:1]([O:3][C:4]([C:6]1([NH:11][C:12]([CH:14]2[CH2:18][CH:17]([O:19][C:20]3[C:29]4[C:24](=[CH:25][C:26]([O:30][CH3:31])=[CH:27][CH:28]=4)[CH:23]=[CH:22][N:21]=3)[CH2:16][N:15]2[C:32](=[O:49])[CH:33]([NH:41][C:42]([O:44][C:45]([CH3:48])([CH3:47])[CH3:46])=[O:43])[CH2:34][CH2:35][CH2:36][O:37][CH2:38]C=C)=[O:13])[CH2:8][CH:7]1[CH:9]=[CH2:10])=[O:5])[CH3:2]>C1C=CC=CC=1.CC1C=C(C)C(N2C(=[Ru](Cl)(Cl)=CC3C=CC=CC=3)N(C3C(C)=CC(C)=CC=3C)CC2)=C(C)C=1.C1CCC(P(C2CCCCC2)C2CCCCC2)CC1>[CH2:1]([O:3][C:4]([C:6]12[CH2:8][CH:7]1[CH:9]=[CH:10][CH2:38][O:37][CH2:36][CH2:35][CH2:34][CH:33]([NH:41][C:42]([O:44][C:45]([CH3:47])([CH3:46])[CH3:48])=[O:43])[C:32](=[O:49])[N:15]1[CH:14]([CH2:18][CH:17]([O:19][C:20]3[C:29]4[C:24](=[CH:25][C:26]([O:30][CH3:31])=[CH:27][CH:28]=4)[CH:23]=[CH:22][N:21]=3)[CH2:16]1)[C:12](=[O:13])[NH:11]2)=[O:5])[CH3:2]

Komponenten

4

Edukt 1

HCID 687495351-{[1-(5-Allyloxy-2-tert-butoxycarbonylamino-pentanoyl)-4-(6-methoxy-isoquinolin-1-yloxy)-pyrrolidine-2-carbonyl]-amino}-2-vinyl-cyclopropanecarboxylic acid ethyl ester2×

Produkt 1

HCID 6874824914-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 esterAusbeute 35 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 11147261(1,3-Dimesitylimidazolidin-2-ylidene)(tricyclohexylphosphine)benzylidene ruthenium dichlorideKatalysatorHCID 241BenzeneLösungsmittel

Reaktionsbedingungen

Temperatur
50 °C

Versuchsvorschrift

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).

Aufarbeitung

  1. concentrationconcentrated in vacuo

Quellen und Nachweise

ORD-Eintrag
ord-bcf417d399b9455081b5512046225e6f
Quelldatensatz
uspto-grants-2007_02
Patentnummer
US07173004B2

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