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 469750ノート

反応式

HRID 469750 の反応式
[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]

参加物

8

反応物 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

生成物 1

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

試薬・触媒・溶媒 3

HCID 9811564Bis(dibenzylideneacetone)palladium触媒HCID 8857Ethyl Acetate溶媒HCID 312751,4-Dioxane溶媒

反応条件

温度
100 °C

実験手順

(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+

後処理

  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%

出典と根拠

ORDレコード
ord-987aff7be2f44470ad9d48f03e47a9df
出典データセット
uspto-grants-2014_01
特許番号
US08629157B2

反応ノート

読み込み中…