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

HRID 1158737

Reaktionsgleichung

Reaktionsgleichung von HRID 1158737
[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]

Komponenten

6

Edukt 3

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

Produkt 1

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

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 6228DimethylformamideLösungsmittelHCID 8857Ethyl AcetateLösungsmittel

Reaktionsbedingungen

Temperatur
100 °C

Versuchsvorschrift

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).

Aufarbeitung

  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)

Quellen und Nachweise

ORD-Eintrag
ord-94f9e109c53941df9694febfc758047c
Quelldatensatz
uspto-grants-2010_10
Patentnummer
US07812018B2

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