Reacción #476400

ord-4b94bd0c37a74bb5a935abf9919c9f06

Ecuación de reacción

C=CCCCCC[C@H](NC(=O)OC(C)(C)C)C(=O)N1C[C@H](Oc2nccc3cc(OC)c(Br)cc23)C[C@H]1C(=O)N[C@]1(C(=O)OCC)C[C@H]1C=C
product
C=CCCCCC[C@H](NC(=O)OC(C)(C)C)C(=O)N1C[C@H](Oc2nccc3cc(OC)c(Br)cc23)C[C@H]1C(=O)N[C@]1(C(=O)OCC)C[C@H]1C=C
Ethyl (1R,2S)-1-[((4R)-4-[(7-bromo-6-methoxyisoquinolin-1-yl)oxy]-1-{(2S)-2-[(t-butoxycarbonyl)amino]non-8-enoyl}-L-prolyl)amino]-2-vinylcyclopropanecarboxylate
→
CCOC(=O)[C@@]12C[C@H]1/C=C\CCCCC[C@H](NC(=O)OC(C)(C)C)C(=O)N1C[C@H](Oc3nccc4cc(OC)c(Br)cc34)C[C@H]1C(=O)N2
title product
Rendimiento 70.1%
CCOC(=O)[C@@]12C[C@H]1/C=C\CCCCC[C@H](NC(=O)OC(C)(C)C)C(=O)N1C[C@H](Oc3nccc4cc(OC)c(Br)cc34)C[C@H]1C(=O)N2
Ethyl (2R,6S,12Z,13aS,14aR,16aS)-2-[(7-bromo-6-methoxyisoquinolin-1-yl)oxy]-6-[(t-butoxycarbonyl)amino]-5,16-dioxo-1,2,3,6,7,8,9,10,11,13a,14,15,16,16a-tetradecahydrocyclopropa[e]pyrrolo[1,2-a][1,4]diazacyclopentadecine-14a(5H)-carboxylate
Rendimiento 70.1%

Reactantes

C=CCCCCC[C@H](NC(=O)OC(C)(C)C)C(=O)N1C[C@H](Oc2nccc3cc(OC)c(Br)cc23)C[C@H]1C(=O)N[C@]1(C(=O)OCC)C[C@H]1C=C
product
C=CCCCCC[C@H](NC(=O)OC(C)(C)C)C(=O)N1C[C@H](Oc2nccc3cc(OC)c(Br)cc23)C[C@H]1C(=O)N[C@]1(C(=O)OCC)C[C@H]1C=C
Ethyl (1R,2S)-1-[((4R)-4-[(7-bromo-6-methoxyisoquinolin-1-yl)oxy]-1-{(2S)-2-[(t-butoxycarbonyl)amino]non-8-enoyl}-L-prolyl)amino]-2-vinylcyclopropanecarboxylate

Reactivos

—
catalyst 1B

Disolventes

ClCCl
dichloromethane

Condiciones de reacción

Condiciones detalladas
See reaction.notes.procedure_details.

Tratamiento posterior

  1. 1
    Temperaturathe reaction mixture was heated
  2. 2
    Temperaturaat reflux under nitrogen for 2 hours
  3. 3
    ConcentraciónThe mixture was concentrated
  4. 4
    Otrochromatographed on silica gel 60
  5. 5
    Lavadoeluting with 5% to 75% EtOAc in hexane

Procedimiento

A solution of the product from Step 3 (200 mg, 0.264 mmol) in dichloromethane (26 mL) was bubbled with nitrogen gas for 30 minutes. Zhan catalyst 1B (19.4 mg, 0.026 mmol) was added, and the reaction mixture was heated at reflux under nitrogen for 2 hours. The mixture was concentrated and chromatographed on silica gel 60, eluting with 5% to 75% EtOAc in hexane to give the title product (135 mg). LRMS (ESI) m/z 729.3 [(M+H)+; calcd for C35H46BrN4O8: 729.3].

Fuente

DOI: 10.6084/m9.figshare.5104873.v1Patente: US08377874B2uspto-grants-2013_02