[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]=1A 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)+.
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