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 244412노트

반응식

HRID 244412 반응식
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]

참가 물질

6

반응물 3

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

생성물 1

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

시약·촉매·용매 2

HCID 3283Diethyl Ether용매HCID 8028Tetrahydrofuran용매2회

실험 절차

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.

후처리

  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

출처 및 근거

ORD 기록
ord-939a2e28c56e43a1b8be58edd9104075
출처 데이터셋
uspto-grants-2014_02
특허 번호
US08658637B2

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