Reacción #45510

Ecuación de reacción

N-[4-(4-amino-7-iodothieno[3,2-c]pyridin-3-yl)-2-methoxyphenyl]-1-methyl-1H-indole-2-carboxamide

sodium tert-butoxide

18-crown-6

benzophenone imine

→

title compound

Rendimiento 64.8%

N-(4-{4-amino-7-[(diphenylmethylene)amino]thieno[3,2-c]pyridin-3-yl}-2-methoxyphenyl)-1-methyl-1H-indole-2-carboxamide

Rendimiento 64.8%

Disolventes

N,N-dimethylformamide

Condiciones de reacción

Tratamiento posterior

1. 1
   TemperaturaThe reaction mixture was cooled to ambient temperature
2. 2
   Concentraciónconcentrated
3. 3
   workup.ADDITIONThe residue was diluted with brine (100 mL)
4. 4
   Extracciónextracted with methanol/dichloromethane (1:33, 3×150 mL)
5. 5
   Secadodried over magnesium sulfate
6. 6
   Filtraciónfiltered
7. 7
   Concentraciónconcentrated
8. 8
   OtroPurification of the residue by flash column chromatography on silica gel which

Procedimiento

A mixture of N-[4-(4-amino-7-iodothieno[3,2-c]pyridin-3-yl)-2-methoxyphenyl]-1-methyl-1H-indole-2-carboxamide (4.03 g, 7.72 mmol), tris(dibenzylideneacetone)dipalladium (0) (0.283 g, 0.31 mmol, 9,9-dimethyl-4-5-bis(diphenylphosphino)xanthene (0.536 g, 0.93 mmol), sodium tert-butoxide (1.00 g, 10.42 mmol), 18-crown-6 (2.75 g, 10.42 mmol), and benzophenone imine (1.16 mL, 6.9 mmol) were combined in N,N-dimethylformamide (100 mL), and the solution was heated at 95° C. for 12 h. The reaction mixture was cooled to ambient temperature and concentrated. The residue was diluted with brine (100 mL) and extracted with methanol/dichloromethane (1:33, 3×150 mL). The organic layers were combined, dried over magnesium sulfate, filtered, and concentrated. Purification of the residue by flash column chromatography on silica gel which had been deactivated with triethylamine (10% by volume of silica gel used), using a gradient of ethyl acetate/heptane (1:3 to 4:1) as the mobile phase afforded the title compound (2.71 g, 4.47 mmol) as a yellow foam: MS: (MH)+ 608; LCMS (Conditions a), Rt 2.27 min.

Fuente