Dimethylformamide → 1-{1-[(3-fluoro-2'-{[(1R)-3-hydroxy-1-methylpropyl]oxy}biphenyl-4-yl)carbonyl]piperidin-4-yl}-3,3-dimethyl-2-oxo-2,3-dihydro-1H-pyrido[2,3-b][1,4]oxazine-7-carbonitrile

HRID 1026592ノート

反応式

HRID 1026592 の反応式
Br[C:2]1[CH:41]=[N:40][C:5]2[O:6][C:7]([CH3:39])([CH3:38])[C:8](=[O:37])[N:9]([CH:10]3[CH2:15][CH2:14][N:13]([C:16]([C:18]4[CH:23]=[CH:22][C:21]([C:24]5[CH:29]=[CH:28][CH:27]=[CH:26][C:25]=5[O:30][C@H:31]([CH3:35])[CH2:32][CH2:33][OH:34])=[CH:20][C:19]=4[F:36])=[O:17])[CH2:12][CH2:11]3)[C:4]=2[CH:3]=1.C(=O)([O-])O.[Na+].[CH3:47][N:48](C)C=O>C1(P(C2C=CC=CC=2)[C-]2C=CC=C2)C=CC=CC=1.[C-]1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=C1.[Fe+2].[Zn].[C-]#N.[Zn+2].[C-]#N.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]>[F:36][C:19]1[CH:20]=[C:21]([C:24]2[CH:29]=[CH:28][CH:27]=[CH:26][C:25]=2[O:30][C@H:31]([CH3:35])[CH2:32][CH2:33][OH:34])[CH:22]=[CH:23][C:18]=1[C:16]([N:13]1[CH2:12][CH2:11][CH:10]([N:9]2[C:8](=[O:37])[C:7]([CH3:39])([CH3:38])[O:6][C:5]3[N:40]=[CH:41][C:2]([C:47]#[N:48])=[CH:3][C:4]2=3)[CH2:15][CH2:14]1)=[O:17]

参加物

8

反応物 3

HCID 6228DimethylformamideHCID 516892Sodium BicarbonateHCID 680059947-bromo-1-{1-[(3-fluoro-2'-{[(1R)-3-hydroxy-1-methylpropyl]oxy}biphenyl-4-yl)carbonyl]piperidin-4-yl}-3,3-dimethyl-1H-pyrido[2,3-b][1,4]oxazin-2(3H)-one

生成物 1

HCID 680059071-{1-[(3-fluoro-2'-{[(1R)-3-hydroxy-1-methylpropyl]oxy}biphenyl-4-yl)carbonyl]piperidin-4-yl}-3,3-dimethyl-2-oxo-2,3-dihydro-1H-pyrido[2,3-b][1,4]oxazine-7-carbonitrile

試薬・触媒・溶媒 4

HCID 11186Zinc cyanide (Zn(CN)2)触媒HCID 23994Zinc触媒HCID 635956Ferrocene-1,1'-bis-(diphenylphosphine)触媒HCID 9811564Bis(dibenzylideneacetone)palladium触媒

反応条件

温度
130 °C

実験手順

To an N,N-dimethylformamide solution (3.0 ml) of 7-bromo-1-{1-[(3-fluoro-2′-{[(1R)-3-hydroxy-1-methylpropyl]oxy}biphenyl-4-yl)carbonyl]piperidin-4-yl}-3,3-dimethyl-1H-pyrido[2,3-b][1,4]oxazin-2(3H)-one (135 mg) were added at room temperature 1,1′-bis(diphenylphosphino)ferrocene (239 mg), zinc powder (1.7 mg), zinc cyanide (15.5 mg) and tris(dibenzylideneacetone)dipalladium (19.8 mg), followed by stirring at 130° C. for 3 hours. The reaction solution was poured into a saturated aqueous sodium hydrogen carbonate solution, and extracted with ethyl acetate. The organic layer was washed sequentially with water and saturated sodium chloride solution, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The resulting residue was purified by silica gel column chromatography to afford 1-{1-[(3-fluoro-2′-{[(1R)-3-hydroxy-1-methylpropyl]oxy}biphenyl-4-yl)carbonyl]piperidin-4-yl}-3,3-dimethyl-2-oxo-2,3-dihydro-1H-pyrido[2,3-b][1,4]oxazine-7-carbonitrile (111 mg).

後処理

  1. extractionextracted with ethyl acetate
  2. washThe organic layer was washed sequentially with water and saturated sodium chloride solution
  3. dry with materialdried over anhydrous sodium sulfate
  4. concentrationconcentrated under reduced pressure
  5. customThe resulting residue was purified by silica gel column chromatography

出典と根拠

ORDレコード
ord-a760c8419cc24de9a53b6bd926ef4fad
出典データセット
uspto-grants-2014_05
特許番号
US08729095B2

反応ノート

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