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

HRID 1886740노트

반응식

HRID 1886740 반응식
[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

참가 물질

6

반응물 4

HCID 962WaterHCID 81531DiisopropylethylamineHCID 12886906(1R,2R)-2-aminocyclopentan-1-ol hydrochlorideHCID 86677431N-cyclopropyl-2-(2,5-dichloropyrimidin-4-yl)-1-(ethoxymethyl)-1H-indole-4-carboxamide

생성물 1

HCID 712806662-{5-chloro-2-[(1R,2R)-2-hydroxycyclopentylamino]pyrimidin-4-yl}-N-cyclopropyl-1-(ethoxymethyl)-1H-indole-4-carboxamide수율 93.6%

시약·촉매·용매 1

HCID 679Dimethyl Sulfoxide용매

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온도
80 °C

실험 절차

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)+.

후처리

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

출처 및 근거

ORD 기록
ord-1c27028976634010ba50d1885c017ffc
출처 데이터셋
uspto-grants-2013_08
특허 번호
US08501166B2

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