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Binap, (A+-)- → 2-(4-tert-butoxycarbonylbenzyl)-6-[4-(5-methyl-3-phenylisoxazol-4-yl)pyrimidin-2-ylamino]-1-oxo-4-phenyl-1,2-dihydroisoquinoline-3-carboxylic Acid Methyl Ester

HRID 750260
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HRID 750260 반응식
C1(P(C2C=CC=CC=2)C2C=CC3C(=CC=CC=3)C=2C2C3C(=CC=CC=3)C=CC=2P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.[CH3:47][O:48][C:49]([C:51]1[N:52]([CH2:69][C:70]2[CH:75]=[CH:74][C:73]([C:76]([O:78][C:79]([CH3:82])([CH3:81])[CH3:80])=[O:77])=[CH:72][CH:71]=2)[C:53](=[O:68])[C:54]2[C:59]([C:60]=1[C:61]1[CH:66]=[CH:65][CH:64]=[CH:63][CH:62]=1)=[CH:58][C:57](Br)=[CH:56][CH:55]=2)=[O:50].[CH3:83][C:84]1[O:88][N:87]=[C:86]([C:89]2[CH:94]=[CH:93][CH:92]=[CH:91][CH:90]=2)[C:85]=1[C:95]1[CH:100]=[CH:99][N:98]=[C:97]([NH2:101])[N:96]=1.CC(C)([O-])C.[Na+]>C([O-])(=O)C.[Pd+2].C([O-])(=O)C.O.C1(C)C=CC=CC=1>[CH3:47][O:48][C:49]([C:51]1[N:52]([CH2:69][C:70]2[CH:75]=[CH:74][C:73]([C:76]([O:78][C:79]([CH3:82])([CH3:81])[CH3:80])=[O:77])=[CH:72][CH:71]=2)[C:53](=[O:68])[C:54]2[C:59]([C:60]=1[C:61]1[CH:66]=[CH:65][CH:64]=[CH:63][CH:62]=1)=[CH:58][C:57]([NH:101][C:97]1[N:96]=[C:95]([C:85]3[C:86]([C:89]4[CH:90]=[CH:91][CH:92]=[CH:93][CH:94]=4)=[N:87][O:88][C:84]=3[CH3:83])[CH:100]=[CH:99][N:98]=1)=[CH:56][CH:55]=2)=[O:50]
참가 물질실험 절차후처리출처 및 근거반응 노트

참가 물질

8

반응물 4

HCID 634876Binap, (A+-)-HCID 27457214-(5-Methyl-3-phenylisoxazol-4-yl)pyrimidin-2-amineHCID 23676156Sodium t-butoxideHCID 691566226-bromo-2-(4-tert-butoxycarbonylbenzyl)-1-oxo-4-phenyl-1,2-dihydroisoquinoline-3-carboxylic Acid Methyl Ester

생성물 1

HCID 69156270
2-(4-tert-butoxycarbonylbenzyl)-6-[4-(5-methyl-3-phenylisoxazol-4-yl)pyrimidin-2-ylamino]-1-oxo-4-phenyl-1,2-dihydroisoquinoline-3-carboxylic Acid Methyl Ester
수율 61%

시약·촉매·용매 3

HCID 167845palladium(II) acetate촉매HCID 962Water용매HCID 1140Toluene용매

실험 절차

To toluene (6 ml) were added palladium(II) acetate (4.1 mg) and rac-2,2′-bis(diphenylphosphino)-1,1′-binaphthyl (34 mg) at room temperature and the mixture was stirred for 5 min. under a nitrogen stream. To the reaction mixture were added 6-bromo-2-(4-tert-butoxycarbonylbenzyl)-1-oxo-4-phenyl-1,2-dihydroisoquinoline-3-carboxylic acid methyl ester (300 mg) and 4-(5-methyl-3-phenylisoxazol-4-yl)pyrimidin-2-ylamine (200 mg) at room temperature and the mixture was stirred for 10 min. under a nitrogen stream. Further, sodium tert-butoxide (70 mg) was added to the reaction mixture at room temperature, and the mixture was heated under reflux under a nitrogen atmosphere for 12 hrs. Water was added to the reaction mixture and the mixture was extracted with ethyl acetate. The organic layer was washed with water, saturated brine and dried over anhydrous sodium sulfate. The solvent was evaporated under reduced pressure and the obtained residue was purified by silica gel column chromatography (hexane-hexane:ethyl acetate=1:1), followed by recrystallization (ethyl acetate-hexane) to give the title compound (240 mg).

후처리

  1. stirringthe mixture was stirred for 10 min. under a nitrogen stream
  2. temperaturethe mixture was heated
  3. temperatureunder reflux under a nitrogen atmosphere for 12 hrs
  4. extractionthe mixture was extracted with ethyl acetate
  5. washThe organic layer was washed with water, saturated brine
  6. dry with materialdried over anhydrous sodium sulfate
  7. customThe solvent was evaporated under reduced pressure
  8. customthe obtained residue was purified by silica gel column chromatography (hexane-hexane:ethyl acetate=1:1)
  9. customfollowed by recrystallization (ethyl acetate-hexane)

출처 및 근거

ORD 기록
ord-da29f78e6f8d4047bcaef94a8fe44945
출처 데이터셋
uspto-grants-2008_07
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US07402595B2

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