Sodium hydride → (R)-N-((6-chloro-2-(4-fluorophenyl)imidazo[1,2-a]pyridin-3-yl)methyl)-4-(1-methylpyrrolidin-3-yloxy)pyrimidin-2-amine

HRID 455104

Reaktionsgleichung

Reaktionsgleichung von HRID 455104
[CH3:1][N:2]1[CH2:6][CH2:5][C@@H:4]([OH:7])[CH2:3]1.[H-].[Na+].Cl[C:11]1[CH:16]=[CH:15][N:14]=[C:13]([NH:17][CH2:18][C:19]2[N:23]3[CH:24]=[C:25]([Cl:28])[CH:26]=[CH:27][C:22]3=[N:21][C:20]=2[C:29]2[CH:34]=[CH:33][C:32]([F:35])=[CH:31][CH:30]=2)[N:12]=1>C1COCC1.C(OCC)(=O)C>[Cl:28][C:25]1[CH:26]=[CH:27][C:22]2[N:23]([C:19]([CH2:18][NH:17][C:13]3[N:14]=[C:15]([O:7][C@@H:4]4[CH2:5][CH2:6][N:2]([CH3:1])[CH2:3]4)[CH:16]=[CH:11][N:12]=3)=[C:20]([C:29]3[CH:30]=[CH:31][C:32]([F:35])=[CH:33][CH:34]=3)[N:21]=2)[CH:24]=1

Komponenten

6

Edukt 3

HCID 24758Sodium hydrideHCID 69513321-Methyl-3-pyrrolidinol, (-)-HCID 583370824-chloro-N-((6-chloro-2-(4-fluorophenyl)imidazo[1,2-a]pyridin-3-yl)methyl)pyrimidin-2-amine

Produkt 1

HCID 58337026(R)-N-((6-chloro-2-(4-fluorophenyl)imidazo[1,2-a]pyridin-3-yl)methyl)-4-(1-methylpyrrolidin-3-yloxy)pyrimidin-2-amine

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 8028TetrahydrofuranLösungsmittelHCID 8857Ethyl AcetateLösungsmittel

Reaktionsbedingungen

Temperatur
80 °C

Versuchsvorschrift

To a solution of (R)-1-methylpyrrolidin-3-ol (66 mg, 0.65 mmol) in THF (3 ml) was added NaH (25 mg, 65% in mineral oil). The mixture was stirred for 30 min and 4-chloro-N-((6-chloro-2-(4-fluorophenyl)imidazo[1,2-a]pyridin-3-yl)methyl)pyrimidin-2-amine (50 mg, 0.13 mmol) was added. The mixture was heated from 65 to 95° C. until the reaction was completed. The mixture was diluted with ethyl acetate and the resulting mixture was washed with saturated NaHCO3 and brine, dried over Na2SO4 and concentrated by evaporation. The crude product was purified by silica gel chromatography (methanol/methylene chloride gradient) to obtain the desired product. 1H-NMR (CDCl3, 400 MHz, δ) 8.23 (s, 1H), 7.69 (m, 2H), 7.52 (d, J=9.5 Hz, 1H), 7.12 (m, 3H), 5.97 (s, 1H), 5.36 (s, 1H), 4.96 (d, J=4.7 Hz, 2H), 2.80 (m, 3H), 2.68 (m, 1H), 2.34 (s, 3H), 2.25 (m, 2H), 1.96 (m, 1H) ppm; m/e 453 (M+H)+.

Aufarbeitung

  1. washthe resulting mixture was washed with saturated NaHCO3 and brine
  2. dry with materialdried over Na2SO4
  3. concentrationconcentrated by evaporation
  4. customThe crude product was purified by silica gel chromatography (methanol/methylene chloride gradient)

Quellen und Nachweise

ORD-Eintrag
ord-c08ef63302d745d69a67db1381f7935b
Quelldatensatz
uspto-grants-2013_07
Patentnummer
US08497278B2

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