Reacción #10662

ord-77836b6fe0cb4c828f1476a14df81196

Ecuación de reacción

CC(C)(C)OC(=O)N[C@H]1CC[C@H](Oc2cccc3cncc(Br)c23)CC1
Intermediate 121
CC(C)(C)OC(=O)N[C@H]1CC[C@H](Oc2cccc3cncc(Br)c23)CC1
trans-N-(tert-butoxycarbonyl)-4-[(4-bromo-5-isoquinolyl)oxy]cyclohexylamine
CN(C)C=O
DMF
→
CC(C)(C)OC(=O)N[C@H]1CC[C@H](Oc2cccc3cncc(C#N)c23)CC1
title compound
CC(C)(C)OC(=O)N[C@H]1CC[C@H](Oc2cccc3cncc(C#N)c23)CC1
trans-N-(tert-butoxycarbonyl)-4-[(4-cyano-5-isoquinolyl)oxy]cyclohexylamine

Reactantes

CC(C)(C)OC(=O)N[C@H]1CC[C@H](Oc2cccc3cncc(Br)c23)CC1
Intermediate 121
CC(C)(C)OC(=O)N[C@H]1CC[C@H](Oc2cccc3cncc(Br)c23)CC1
trans-N-(tert-butoxycarbonyl)-4-[(4-bromo-5-isoquinolyl)oxy]cyclohexylamine
CN(C)C=O
DMF

Reactivos

[C-]#N.[C-]#N.[Zn+2]
zinc cyanide
O=C(/C=C/c1ccccc1)/C=C/c1ccccc1.O=C(/C=C/c1ccccc1)/C=C/c1ccccc1.O=C(/C=C/c1ccccc1)/C=C/c1ccccc1.[Pd].[Pd]
tris(dibenzylideneacetone)dipalladium(0)
[Fe+2].c1ccc(P(c2ccccc2)[c-]2cccc2)cc1.c1ccc(P(c2ccccc2)[c-]2cccc2)cc1
1,1′-bis(diphenylphosphino)ferrocene

Condiciones de reacción

Temperatura
120°CELSIUS
Condiciones detalladas
See reaction.notes.procedure_details.

Tratamiento posterior

  1. 1
    ConcentraciónThe reaction mixture was concentrated under reduced pressure
  2. 2
    Otrothe residue was purified by silica gel column chromatography (n-hexane:ethyl acetate=1:1)

Procedimiento

A suspension of Intermediate 121 (113.7 mg), zinc cyanide (19.4 mg, Wako Pure Chemical Industries), tris(dibenzylideneacetone)dipalladium(0) (24.0 mg) and 1,1′-bis(diphenylphosphino)ferrocene (35.3 mg, Tokyo Kasei Kogyo) in DMF (2 ml) was stirred at 120° C. for 19 hours. The reaction mixture was concentrated under reduced pressure, and the residue was purified by silica gel column chromatography (n-hexane:ethyl acetate=1:1) to obtain the title compound (34.9 mg).

Fuente

DOI: 10.6084/m9.figshare.5104873.v1Patente: US07094789B2uspto-grants-2006_08