Sodium ethoxide → 9-Chloro-6-[1-(difluoromethoxy)-2,2,2-trifluoroethyl]-1-(2-ethoxy-4,6-dimethylpyrimidin-5-yl)-1,2,3,4-tetrahydropyrimido[1,2-a]benzimidazole

HRID 1399125ノート

反応式

HRID 1399125 の反応式
[Cl:1][C:2]1[C:10]2[N:9]=[C:8]3[N:11]([C:15]4[C:16]([CH3:23])=[N:17][C:18](Cl)=[N:19][C:20]=4[CH3:21])[CH2:12][CH2:13][CH2:14][N:7]3[C:6]=2[C:5]([CH:24]([O:29][CH:30]([F:32])[F:31])[C:25]([F:28])([F:27])[F:26])=[CH:4][CH:3]=1.[O-:33][CH2:34][CH3:35].[Na+]>C(O)C>[Cl:1][C:2]1[C:10]2[N:9]=[C:8]3[N:11]([C:15]4[C:16]([CH3:23])=[N:17][C:18]([O:33][CH2:34][CH3:35])=[N:19][C:20]=4[CH3:21])[CH2:12][CH2:13][CH2:14][N:7]3[C:6]=2[C:5]([CH:24]([O:29][CH:30]([F:31])[F:32])[C:25]([F:27])([F:26])[F:28])=[CH:4][CH:3]=1

参加物

4

反応物 2

HCID 2723922Sodium ethoxideHCID 577862249-Chloro-1-(2-chloro-4,6-dimethylpyrimidin-5-yl)-6-[1-(difluoromethoxy)-2,2,2-trifluoroethyl]-1,2,3,4-tetrahydropyrimido[1,2-a]benzimidazole

生成物 1

HCID 577861889-Chloro-6-[1-(difluoromethoxy)-2,2,2-trifluoroethyl]-1-(2-ethoxy-4,6-dimethylpyrimidin-5-yl)-1,2,3,4-tetrahydropyrimido[1,2-a]benzimidazole

試薬・触媒・溶媒 1

HCID 702Ethanol溶媒

反応条件

温度
50 °C

実験手順

A mixture of 9-chloro-1-(2-chloro-4,6-dimethylpyrimidin-5-yl)-6-[1-(difluoromethoxy)-2,2,2-trifluoroethyl]-1,2,3,4-tetrahydropyrimido[1,2-a]benzimidazole (142 mg, 0.286 mmol) and sodium ethoxide (20% solution in ethanol, 292 mg, 0.858 mmol) in ethanol (1.0 mL) was stirred at 50° C. for 5 hr. The mixture was concentrated in vacuo, diluted with water and extracted with ethyl acetate. The combined organic layer was washed with brine, dried over anhydrous magnesium sulfate, filtered and concentrated in vacuo. The residue was purified by flash column chromatography on silica gel eluting with a 50-100% ethyl acetate/n-hexane gradient mixture. The filtrate was concentrated in vacuo to give the solid, which was purified by preparative HPLC to give a mixture contained an intermediate of the title compound as the trifluoroacetic acid salt. The mixture was washed with aqueous sodium hydrogen carbonate and extracted with ethyl acetate. The extract was washed with brine, dried over magnesium sulfate, filtered and concentrated in vacuo to give the solid, which was recrystallized from ethyl acetate/n-hexane to give the title compound as a colorless crystal (65.3 mg, 0.286 mmol, 45%).

後処理

  1. concentrationThe mixture was concentrated in vacuo
  2. additiondiluted with water
  3. extractionextracted with ethyl acetate
  4. washThe combined organic layer was washed with brine
  5. dry with materialdried over anhydrous magnesium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo
  8. customThe residue was purified by flash column chromatography on silica gel eluting with a 50-100% ethyl acetate/n-hexane gradient mixture
  9. concentrationThe filtrate was concentrated in vacuo
  10. customto give the solid, which
  11. customwas purified by preparative HPLC
  12. customto give a mixture

出典と根拠

ORDレコード
ord-9da76ebd9547438593adce8f3c50726a
出典データセット
uspto-grants-2014_12
特許番号
US08901141B2

反応ノート

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