Sodium hydride → 5-[6-(2-Oxo-pyrrolidin-1-ylmethyl)-pyrimidin-4-yloxy]-indole-1-carboxylic acid (4-fluoro-3-trifluoromethyl-phenyl)-amide

HRID 884597

Reaktionsgleichung

Reaktionsgleichung von HRID 884597
[F:1][C:2]1[CH:7]=[CH:6][C:5]([NH:8][C:9]([N:11]2[C:19]3[C:14](=[CH:15][C:16]([O:20][C:21]4[CH:26]=[C:25]([CH2:27][NH:28][C:29](=[O:34])[CH2:30][CH2:31][CH2:32]Br)[N:24]=[CH:23][N:22]=4)=[CH:17][CH:18]=3)[CH:13]=[CH:12]2)=[O:10])=[CH:4][C:3]=1[C:35]([F:38])([F:37])[F:36].[H-].[Na+]>C1COCC1>[F:1][C:2]1[CH:7]=[CH:6][C:5]([NH:8][C:9]([N:11]2[C:19]3[C:14](=[CH:15][C:16]([O:20][C:21]4[CH:26]=[C:25]([CH2:27][N:28]5[CH2:32][CH2:31][CH2:30][C:29]5=[O:34])[N:24]=[CH:23][N:22]=4)=[CH:17][CH:18]=3)[CH:13]=[CH:12]2)=[O:10])=[CH:4][C:3]=1[C:35]([F:38])([F:37])[F:36]

Komponenten

4

Edukt 2

HCID 24758Sodium hydrideHCID 593944875-{6-[(4-Bromo-butyrylamino)-methyl]-pyrimidin-4-yloxy}-indole-1-carboxylic acid (4-fluoro-3-trifluoromethyl-phenyl)-amide

Produkt 1

HCID 593940095-[6-(2-Oxo-pyrrolidin-1-ylmethyl)-pyrimidin-4-yloxy]-indole-1-carboxylic acid (4-fluoro-3-trifluoromethyl-phenyl)-amide

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 8028TetrahydrofuranLösungsmittel

Reaktionsbedingungen

Temperatur
0 °C

Versuchsvorschrift

5-{6-[(4-Bromo-butyrylamino)-methyl]-pyrimidin-4-yloxy}-indole-1-carboxylic acid (4-fluoro-3-trifluoromethyl-phenyl)-amide (0.353 g, 0.595 mmol) is dissolved in 10 mL THF and cooled to 0° C. Sodium hydride (63 mg, 1.5 mmol, 60% in mineral oil) is added and the reaction is allowed to warm to room temperature overnight. The reaction is quenched with water and diluted with ethyl acetate. The organic layer is removed, dried, and concentrated and the residue is separated via semi-prep HPLC (C18; 20-100% I/H2O with 0.1% TFA) to provide the title compound. MS (ESI) m/z 514.9 (M+1); 1H NMR (400 MHz, DMSO-d6) δ ppm 10.40 (s, 1H), 8.68 (d, J=1.01 Hz, 1H), 8.28 (d, J=9.09 Hz, 1H), 8.09-8.12 (m, 2H), 7.99-8.03 (m, 1H), 7.57 (t, J=9.85 Hz, 1H), 7.49 (d, J=2.27 Hz, 1H), 7.15 (dd, J=8.97, 2.40 Hz, 1H), 6.94 (d, J=1.01 Hz, 1H), 6.81 (d, J=3.79 Hz, 1H), 4.45 (s, 2H), 3.42 (t, J=6.95 Hz, 2H), 2.29-2.34 (m, 3H), 2.00 (t, J=7.58 Hz, 2H).

Aufarbeitung

  1. temperatureto warm to room temperature overnight
  2. customThe reaction is quenched with water
  3. additiondiluted with ethyl acetate
  4. customThe organic layer is removed
  5. customdried
  6. concentrationconcentrated
  7. customthe residue is separated via semi-prep HPLC (C18; 20-100% I/H2O with 0.1% TFA)

Quellen und Nachweise

ORD-Eintrag
ord-6961029cfa464330a1d31996ec922d4e
Quelldatensatz
uspto-grants-2012_08
Patentnummer
US08242125B2

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