Reacción #1973922

Ecuación de reacción

water

N-cyclopropyl-2-(2,5-dichloropyrimidin-4-yl)-1-(ethoxymethyl)-1H-indole-4-carboxamide

(1R,2R)-2-aminocyclopentanol hydrochloride

DIPEA

→

2-{5-chloro-2-[(1R,2R)-2-hydroxycyclopentylamino]pyrimidin-4-yl}-N-cyclopropyl-1-(ethoxymethyl)-1H-indole-4-carboxamide

Rendimiento 93.6%

Disolventes

DMSO

Condiciones de reacción

Tratamiento posterior

1. 1
   Extracciónextracted with EA (2×500 mL)
2. 2
   LavadoThe combined extracts are washed with aqueous saturated sodium chloride (500 mL)
3. 3
   Secadodried over Na2SO4
4. 4
   Concentraciónconcentrated in vacuo
5. 5
   OtroThe residue is purified by chromatography on silica gel

Procedimiento

A mixture of N-cyclopropyl-2-(2,5-dichloropyrimidin-4-yl)-1-(ethoxymethyl)-1H-indole-4-carboxamide (30 g, 75 mmol), (1R,2R)-2-aminocyclopentanol hydrochloride (12.3 g, 90 mmol) and DIPEA (37.5 mL, 225 mmol) in DMSO (150 mL) is stirred at 80° C. for 16 h, then poured into water (1 L), and extracted with EA (2×500 mL). The combined extracts are washed with aqueous saturated sodium chloride (500 mL), dried over Na2SO4 and concentrated in vacuo. The residue is purified by chromatography on silica gel to give 2-{5-chloro-2-[(1R,2R)-2-hydroxycyclopentylamino]pyrimidin-4-yl}-N-cyclopropyl-1-(ethoxymethyl)-1H-indole-4-carboxamide (33 g, 93%). MS (m/z): 470 (35Cl) and 472 (37Cl) (M+H)+.

Fuente