7-Bromo-3-(4-fluorophenyl)imidazo[1,5-a]pyridine → 1-[1-(2,2-Dimethyl-1,3-dioxolan-4-ylmethyl)-1H-indol-3-yl]-2,2,2-trifluoro-1-[3-(4-fluorophenyl)imidazo[1,5-a]pyridin-7-yl]ethanol

HRID 244476ノート

反応式

HRID 244476 の反応式
Br[C:2]1[CH:7]=[CH:6][N:5]2[C:8]([C:11]3[CH:16]=[CH:15][C:14]([F:17])=[CH:13][CH:12]=3)=[N:9][CH:10]=[C:4]2[CH:3]=1.C([Li])CCC.[CH3:23][C:24]1([CH3:45])[O:28][CH:27]([CH2:29][N:30]2[C:38]3[C:33](=[CH:34][CH:35]=[CH:36][CH:37]=3)[C:32]([C:39](=[O:44])[C:40]([F:43])([F:42])[F:41])=[CH:31]2)[CH2:26][O:25]1>C1COCC1>[CH3:23][C:24]1([CH3:45])[O:28][CH:27]([CH2:29][N:30]2[C:38]3[C:33](=[CH:34][CH:35]=[CH:36][CH:37]=3)[C:32]([C:39]([C:2]3[CH:7]=[CH:6][N:5]4[C:8]([C:11]5[CH:16]=[CH:15][C:14]([F:17])=[CH:13][CH:12]=5)=[N:9][CH:10]=[C:4]4[CH:3]=3)([OH:44])[C:40]([F:43])([F:42])[F:41])=[CH:31]2)[CH2:26][O:25]1

参加物

5

反応物 3

HCID 594372397-Bromo-3-(4-fluorophenyl)imidazo[1,5-a]pyridineHCID 594372891-[1-(2,2-dimethyl-1,3-dioxolan-4-ylmethyl)-1H-indol-3-yl]-2,2,2-trifluoroethanoneHCID 178418339Butyllithium

生成物 1

HCID 249598181-[1-(2,2-Dimethyl-1,3-dioxolan-4-ylmethyl)-1H-indol-3-yl]-2,2,2-trifluoro-1-[3-(4-fluorophenyl)imidazo[1,5-a]pyridin-7-yl]ethanol収率 33.7%

試薬・触媒・溶媒 1

HCID 8028Tetrahydrofuran溶媒2 回

実験手順

To a chilled (−78° C.) solution of 7-bromo-3-(4-fluorophenyl)imidazo[1,5-a]pyridine (160 mg, 0.55 mmol) in anhydrous THF (3 mL) was added n-butyllithium (275 μL of a 2.5 M solution in hexanes, 0.69 mmol). After 2 minutes, a chilled (−78° C.) solution of 1-[1-(2,2-dimethyl-1,3-dioxolan-4-ylmethyl)-1H-indol-3-yl]-2,2,2-trifluoroethanone (240 mg, 0.73 mmol) in 1 mL of THF was added. After 60 minutes, the mixture was quenched with brine (50 mL) and extracted with ethyl acetate. The combined organic layers were washed with water, dried over anhydrous sodium sulfate, and concentrated in vacuo to afford a yellow oil. The residue was purified by column chromatography over silica gel eluting with 0-75% ethyl acetate in hexanes and fractions corresponding to a MS m/z 540 (MH+) peak were pooled and concentrated in vacuo to afford 100 mg of the title compound as a light yellow solid.

後処理

  1. additionwas added
  2. waitAfter 60 minutes
  3. customthe mixture was quenched with brine (50 mL)
  4. extractionextracted with ethyl acetate
  5. washThe combined organic layers were washed with water
  6. dry with materialdried over anhydrous sodium sulfate
  7. concentrationconcentrated in vacuo
  8. customto afford a yellow oil
  9. customThe residue was purified by column chromatography over silica gel eluting with 0-75% ethyl acetate in hexanes and fractions corresponding to a MS m/z 540 (MH+) peak
  10. concentrationconcentrated in vacuo

出典と根拠

ORDレコード
ord-4e0b77b5eae8429e8be3ff552f1b29a8
出典データセット
uspto-grants-2014_02
特許番号
US08658637B2

反応ノート

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