Cesium carbonate → tert-butyl (1-{[2-amino-3-(aminocarbonyl)-9H-pyrido[2,3-b]indol-9-yl]methyl}cyclopropyl)carbamate

HRID 1158737

반응식

HRID 1158737 반응식
[NH2:1][C:2]1[C:3]([C:15]([NH2:17])=[O:16])=[CH:4][C:5]2[C:13]3[C:8](=[CH:9][CH:10]=[CH:11][CH:12]=3)[NH:7][C:6]=2[N:14]=1.C(=O)([O-])[O-].[Cs+].[Cs+].[C:24]([O:28][C:29](=[O:36])[NH:30][C:31]1([CH2:34]I)[CH2:33][CH2:32]1)([CH3:27])([CH3:26])[CH3:25]>CN(C)C=O.C(OCC)(=O)C>[C:24]([O:28][C:29](=[O:36])[NH:30][C:31]1([CH2:34][N:7]2[C:8]3[C:13](=[CH:12][CH:11]=[CH:10][CH:9]=3)[C:5]3[CH:4]=[C:3]([C:15]([NH2:17])=[O:16])[C:2]([NH2:1])=[N:14][C:6]2=3)[CH2:32][CH2:33]1)([CH3:27])([CH3:25])[CH3:26]

참가 물질

6

반응물 3

HCID 10796Cesium carbonateHCID 152709842-amino-9H-pyrido[2,3-b]indole-3-carboxamideHCID 86648312HCID 86648312, 화합물

생성물 1

HCID 24901061tert-butyl (1-{[2-amino-3-(aminocarbonyl)-9H-pyrido[2,3-b]indol-9-yl]methyl}cyclopropyl)carbamate수율 13%

시약·촉매·용매 2

HCID 6228Dimethylformamide용매HCID 8857Ethyl Acetate용매

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온도
100 °C

실험 절차

To a stirred solution of 2-amino-9H-pyrido[2,3-b]indole-3-carboxamide (5, 318 mg, 1.41 mmol) in N,N-dimethylformamide (17 mL) was added powdered cesium carbonate (2.29 g, 7.03 mmol), tert-butyl[1-(iodomethyl)cyclopropyl]carbamate (2.26 g, 7.61 mmol, prepared from the corresponding alcohol (J. Med. Chem. 1988, 31, 1694-7) following the procedure detailed in the preparation of xxvii below) was added. The mixture was heated at 100° C. under nitrogen for 2 h. The reaction was cooled to room temperature, diluted with ethyl acetate (150 mL) and washed thrice with water and twice with brine. The extracts were dried over magnesium sulfate, filtered and concentrated. The crude product was purified by silica gel chromatography (95/5 methylene chloride/methanol to 93/7 methylene chloride/methanol gradient) to afford the titled product (63, 75 mg, 13%). NH4OAc Standard conditions. DAD Retention time =7.29 min. M+H=396; 1H NMR (300 MHz, DMSO-d6): δ 8.72 (s, 1H), 7.79 (d, J=7.3 Hz, 1H), 7.54-7.41 (m, 2H), 7.26 (dd, J=7.3 Hz, 1H), 7.20-7.11 (m, 2H), 4.34 (s, 2H), 1.35 (s, 9H), 1.18-1.05 (m, 2H), 0.65-0.54 (m, 2H).

후처리

  1. additionwas added
  2. temperatureThe reaction was cooled to room temperature
  3. washwashed thrice with water
  4. dry with materialThe extracts were dried over magnesium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customThe crude product was purified by silica gel chromatography (95/5 methylene chloride/methanol to 93/7 methylene chloride/methanol gradient)

출처 및 근거

ORD 기록
ord-94f9e109c53941df9694febfc758047c
출처 데이터셋
uspto-grants-2010_10
특허 번호
US07812018B2

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