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

反応式

HRID 455104 の反応式
[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

参加物

6

反応物 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

生成物 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

試薬・触媒・溶媒 2

HCID 8028Tetrahydrofuran溶媒HCID 8857Ethyl Acetate溶媒

反応条件

温度
80 °C

実験手順

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)+.

後処理

  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)

出典と根拠

ORDレコード
ord-c08ef63302d745d69a67db1381f7935b
出典データセット
uspto-grants-2013_07
特許番号
US08497278B2

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