Reacción #77513

ord-e9ac4aa747d3472587e973ff00ac2a98

Ecuación de reacción

CC(C)[C@H]1OC[C@H](N)CO1
trans 2-isopropyl-[1,3]dioxan-5-ylamine
Oc1ccc(Cc2cnc(Cl)c3ccccc23)cn1
1-chloro-4-[(6-hydroxy-pyridin-3-yl)methyl]-isoquinoline
CCCCN(CCCC)CCCC
tributylamine
→
CC(C)[C@H]1OC[C@H](Nc2ncc(Cc3ccc(O)nc3)c3ccccc23)CO1
trans 1-(2-isopropyl-[1,3]dioxan-5-ylamino)-4-[(6-hydroxy-pyridin-3-yl)methyl]-isoquinoline

Reactantes

CC(C)[C@H]1OC[C@H](N)CO1
trans 2-isopropyl-[1,3]dioxan-5-ylamine
Oc1ccc(Cc2cnc(Cl)c3ccccc23)cn1
1-chloro-4-[(6-hydroxy-pyridin-3-yl)methyl]-isoquinoline
CCCCN(CCCC)CCCC
tributylamine

Reactivos

Ninguno

Disolventes

CCOC(C)=O
EtOAc
O=C([O-])O.[Na+]
NaHCO3

Condiciones de reacción

Condiciones detalladas
See reaction.notes.procedure_details.

Tratamiento posterior

  1. 1
    Otrothe aqueous layer is separated
  2. 2
    Extracciónextracted twice with EtOAc
  3. 3
    LavadoThe organic phases are washed with brine
  4. 4
    Secadodried (Na2SO4)
  5. 5
    Concentraciónconcentrated in vaccuo

Procedimiento

In a sealed glass bottle under N2-atmosphere, 424 mg (2.92 mmol) of trans 2-isopropyl-[1,3]dioxan-5-ylamine, 396 mg (1.46 mmol) of 1-chloro-4-[(6-hydroxy-pyridin-3-yl)methyl]-isoquinoline (contains 1-iodo derivative) and 2 ml of tributylamine are stirred at 150° C. for 48 h. The resulting mixture is diluted with EtOAc and NaHCO3-solution, the aqueous layer is separated and extracted twice with EtOAc. The organic phases are washed with brine, dried (Na2SO4) and concentrated in vaccuo. “Reversed Phase” medium-pressure chromatography (water/acetonitrile/TFA) yields trans 1-(2-isopropyl-[1,3]dioxan-5-ylamino)-4-[(6-hydroxy-pyridin-3-yl)methyl]-isoquinoline; FAB-MS; (M+H)+=286; HPLC(gradient20-100) tRet=8.6.

Fuente

DOI: 10.6084/m9.figshare.5104873.v1Patente: US06706731B2uspto-grants-2004_03