5-Bromo-2-methoxy-3-methylpyridine → 2,2,2-Trifluoro-1-[1-(4-fluorophenyl)-1H-indazol-5-yl]-1-(5-methyl-6-methoxypyridin-3-yl)ethanol

HRID 244412ノート

反応式

HRID 244412 の反応式
Br[C:2]1[CH:3]=[C:4]([CH3:10])[C:5]([O:8][CH3:9])=[N:6][CH:7]=1.C([Li])CCC.[F:16][C:17]([F:37])([F:36])[C:18]([C:20]1[CH:21]=[C:22]2[C:26](=[CH:27][CH:28]=1)[N:25]([C:29]1[CH:34]=[CH:33][C:32]([F:35])=[CH:31][CH:30]=1)[N:24]=[CH:23]2)=[O:19]>C1COCC1.CCOCC>[F:37][C:17]([F:16])([F:36])[C:18]([C:20]1[CH:21]=[C:22]2[C:26](=[CH:27][CH:28]=1)[N:25]([C:29]1[CH:34]=[CH:33][C:32]([F:35])=[CH:31][CH:30]=1)[N:24]=[CH:23]2)([C:2]1[CH:7]=[N:6][C:5]([O:8][CH3:9])=[C:4]([CH3:10])[CH:3]=1)[OH:19]

参加物

6

反応物 3

HCID 225911765-Bromo-2-methoxy-3-methylpyridineHCID 579432692,2,2-trifluoro-1-[1-(4-fluorophenyl)-1H-indazol-5-yl]ethanoneHCID 178418339Butyllithium

生成物 1

HCID 594373112,2,2-Trifluoro-1-[1-(4-fluorophenyl)-1H-indazol-5-yl]-1-(5-methyl-6-methoxypyridin-3-yl)ethanol

試薬・触媒・溶媒 2

HCID 3283Diethyl Ether溶媒HCID 8028Tetrahydrofuran溶媒2 回

実験手順

To a chilled (−78° C.) solution of 5-bromo-3-methyl-2-methoxypyridine (1.56 mmol) in 2 mL THF was added dropwise n-butyllithium (1.71 mmol from a 2.5 M solution in hexanes). The mixture was stirred for 30 minutes and then 2,2,2-trifluoro-1-[1-(4-fluorophenyl)-1H-indazol-5-yl]ethanone (1.39 mmol) in 3 mL THF was added. After 30 minutes, the mixture was diluted with ether and quenched with aqueous ammonium chloride. The organic layer was washed with brine and dried over magnesium sulfate. Removal of the volatiles in vacuo provided a residue which was purified by Combiflash chromatography using ethyl acetate-hexane. The product-rich fractions were concentrated in vacuo to provide the title compound.

後処理

  1. waitAfter 30 minutes
  2. customquenched with aqueous ammonium chloride
  3. washThe organic layer was washed with brine
  4. dry with materialdried over magnesium sulfate
  5. customRemoval of the volatiles in vacuo
  6. customprovided a residue which
  7. customwas purified by Combiflash chromatography
  8. concentrationThe product-rich fractions were concentrated in vacuo

出典と根拠

ORDレコード
ord-939a2e28c56e43a1b8be58edd9104075
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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