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 1026592노트

반응식

HRID 1026592 반응식
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]

참가 물질

8

반응물 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

생성물 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

시약·촉매·용매 4

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

반응 조건

온도
130 °C

실험 절차

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).

후처리

  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

출처 및 근거

ORD 기록
ord-a760c8419cc24de9a53b6bd926ef4fad
출처 데이터셋
uspto-grants-2014_05
특허 번호
US08729095B2

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