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

HRID 1886740Notes

Reaction equation

[CH:1]1([NH:4][C:5]([C:7]2[C:8]3[CH:9]=[C:10]([C:20]4[C:25]([Cl:26])=[CH:24][N:23]=[C:22](Cl)[N:21]=4)[N:11]([CH2:16][O:17][CH2:18][CH3:19])[C:12]=3[CH:13]=[CH:14][CH:15]=2)=[O:6])[CH2:3][CH2:2]1.Cl.[NH2:29][C@@H:30]1[CH2:34][CH2:33][CH2:32][C@H:31]1[OH:35].CCN(C(C)C)C(C)C.O>CS(C)=O>[Cl:26][C:25]1[C:20]([C:10]2[N:11]([CH2:16][O:17][CH2:18][CH3:19])[C:12]3[CH:13]=[CH:14][CH:15]=[C:7]([C:5]([NH:4][CH:1]4[CH2:3][CH2:2]4)=[O:6])[C:8]=3[CH:9]=2)=[N:21][C:22]([NH:29][C@@H:30]2[CH2:34][CH2:33][CH2:32][C@H:31]2[OH:35])=[N:23][CH:24]=1

Participants

Conditions

Temperature: 80 °C

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)+.

Workup

extractionextracted with EA (2×500 mL)
washThe combined extracts are washed with aqueous saturated sodium chloride (500 mL)
dry with materialdried over Na2SO4
concentrationconcentrated in vacuo
customThe residue is purified by chromatography on silica gel

Sources & evidence

ORD record: ord-1c27028976634010ba50d1885c017ffc
Source dataset: uspto-grants-2013_08
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08501166B2

Reaction notes

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