Cesium carbonate → (S)-1-(5-fluoro-6-methyl-pyridin-2-yl)-5-oxo-pyrrolidine-2-carboxylic acid (3-tert-butyl-isoxazol-5-yl)amide

HRID 469750노트

반응식

HRID 469750 반응식
[C:1]([C:5]1[CH:9]=[C:8]([NH:10][C:11]([C@@H:13]2[CH2:17][CH2:16][C:15](=[O:18])[NH:14]2)=[O:12])[O:7][N:6]=1)([CH3:4])([CH3:3])[CH3:2].CC1(C)C2C(=C(P(C3C=CC=CC=3)C3C=CC=CC=3)C=CC=2)OC2C(P(C3C=CC=CC=3)C3C=CC=CC=3)=CC=CC1=2.C(=O)([O-])[O-].[Cs+].[Cs+].Br[C:68]1[N:73]=[C:72]([CH3:74])[C:71]([F:75])=[CH:70][CH:69]=1>O1CCOCC1.C(OCC)(=O)C.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[C:1]([C:5]1[CH:9]=[C:8]([NH:10][C:11]([C@@H:13]2[CH2:17][CH2:16][C:15](=[O:18])[N:14]2[C:68]2[CH:69]=[CH:70][C:71]([F:75])=[C:72]([CH3:74])[N:73]=2)=[O:12])[O:7][N:6]=1)([CH3:4])([CH3:2])[CH3:3]

참가 물질

8

반응물 4

HCID 10796Cesium carbonateHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 27831806-Bromo-3-fluoro-2-methylpyridineHCID 67454707(S)-5-oxo-pyrrolidine-2-carboxylic acid (3-tert-butyl-isoxazol-5-yl)-amide

생성물 1

HCID 67457597(S)-1-(5-fluoro-6-methyl-pyridin-2-yl)-5-oxo-pyrrolidine-2-carboxylic acid (3-tert-butyl-isoxazol-5-yl)amide수율 27.3%

시약·촉매·용매 3

HCID 9811564Bis(dibenzylideneacetone)palladium촉매HCID 8857Ethyl Acetate용매HCID 312751,4-Dioxane용매

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온도
100 °C

실험 절차

(S)-5-Oxo-pyrrolidine-2-carboxylic acid (3-tert-butyl-isoxazol-5-yl)-amide (300 mg, 1.19 mmol), tris(dibenzylideneacteone)dipalladium (0) (32.80 mg, 0.036 mmol), Xantphos ® (62.20 mg, 0.011 mmol), caesium carbonate (654.16 mg, 2.01 mmol) and 6-bromo-3-fluoro-2-methylpyridine (226.90, 1.20 mmol) are charged to a vessel, diluted with dioxane (anhydrous, 3 ml) and heated to 100° C. overnight. On completion, the reaction is diluted with ethyl acetate and partitioned between water. The organic phase is separated, dried over sodium sulphate and the solvents removed under vacuum. The crude residue is purified by flash column chromatography eluting with a gradient solution of heptane/ethyl acetate 0-50% to isolate 117 mg of title compound as a white solid, yield 27%. ESI m/z 361=MH+

후처리

  1. custompartitioned between water
  2. customThe organic phase is separated
  3. dry with materialdried over sodium sulphate
  4. customthe solvents removed under vacuum
  5. customThe crude residue is purified by flash column chromatography
  6. washeluting with a gradient solution of heptane/ethyl acetate 0-50%

출처 및 근거

ORD 기록
ord-987aff7be2f44470ad9d48f03e47a9df
출처 데이터셋
uspto-grants-2014_01
특허 번호
US08629157B2

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