Reaction #1973922

Reaction equation

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

Yield 93.6%

Solvents

DMSO

Conditions

Workup

1. 1
   Extractionextracted with EA (2×500 mL)
2. 2
   WashThe combined extracts are washed with aqueous saturated sodium chloride (500 mL)
3. 3
   Dryingdried over Na2SO4
4. 4
   Concentrationconcentrated in vacuo
5. 5
   OtherThe residue is purified by chromatography on silica gel

Procedure

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)+.

Source