Cesium carbonate → (4-{5-[(5-Cyclopropyl-1,2-oxazol-3-yl)amino]-1-methyl-6-oxo-1,6-dihydro-pyridin-3-yl}-2-{4,4-dimethyl-9-oxo-1,10-diazatricyclo[6.4.0.02,6]dodeca-2(6),7-dien-10-yl}pyridin-3-yl)methyl Acetate

HRID 1022190노트

반응식

HRID 1022190 반응식
[CH:1]1([C:4]2[O:8][N:7]=[C:6]([NH2:9])[CH:5]=2)[CH2:3][CH2:2]1.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:52]([O:55][CH2:56][C:57]1[C:58]([N:72]2[CH2:83][CH2:82][N:81]3[C:74](=[CH:75][C:76]4[CH2:77][C:78]([CH3:85])([CH3:84])[CH2:79][C:80]=43)[C:73]2=[O:86])=[N:59][CH:60]=[CH:61][C:62]=1[C:63]1[CH:68]=[C:67](Br)[C:66](=[O:70])[N:65]([CH3:71])[CH:64]=1)(=[O:54])[CH3:53].C([O-])([O-])=O.[Cs+].[Cs+]>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].O1CCOCC1>[C:52]([O:55][CH2:56][C:57]1[C:58]([N:72]2[CH2:83][CH2:82][N:81]3[C:74](=[CH:75][C:76]4[CH2:77][C:78]([CH3:85])([CH3:84])[CH2:79][C:80]=43)[C:73]2=[O:86])=[N:59][CH:60]=[CH:61][C:62]=1[C:63]1[CH:68]=[C:67]([NH:9][C:6]2[CH:5]=[C:4]([CH:1]3[CH2:3][CH2:2]3)[O:8][N:7]=2)[C:66](=[O:70])[N:65]([CH3:71])[CH:64]=1)(=[O:54])[CH3:53]

참가 물질

7

반응물 4

HCID 10796Cesium carbonateHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 150524865-Cyclopropyl-1,2-oxazol-3-amineHCID 86684396[4-(5-Bromo-1-methyl-6-oxo-1,6-dihydropyridin-3-yl)-2-{4,4-dimethyl-9-oxo-1,10-diazatricyclo[6.4.0.02,6]dodeca-2(6),7-dien-10-yl}pyridin-3-yl]methyl Acetate

생성물 1

HCID 86684561(4-{5-[(5-Cyclopropyl-1,2-oxazol-3-yl)amino]-1-methyl-6-oxo-1,6-dihydro-pyridin-3-yl}-2-{4,4-dimethyl-9-oxo-1,10-diazatricyclo[6.4.0.02,6]dodeca-2(6),7-dien-10-yl}pyridin-3-yl)methyl Acetate수율 32%

시약·촉매·용매 2

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

실험 절차

A 25-mL single-neck round-bottomed flask equipped with a magnetic stirrer and a reflux condenser was charged with 5-cyclopropylisoxazol-3-amine (80 mg, 0.65 mmol), XantPhos (29 mg, 0.050 mmol), Pd2dba3 (45 mg, 0.050 mmol), [4-(5-bromo-1-methyl-6-oxo-1,6-dihydropyridin-3-yl)-2-{4,4-dimethyl-9-oxo-1,10-diazatricy-clo[6.4.0.02,6]dodeca-2(6),7-dien-10-yl}pyridin-3-yl]methyl acetate 273a (350 mg, 0.65 mmol), Cs2CO3 (390 mg, 1.2 mmol), and 1,4-dioxane (10 mL). After bubbling nitrogen through the resulting mixture for 10 minutes, it was heated at reflux for 2 h. The mixture was then evaporated under reduced pressure and the residue was partitioned between ethyl acetate (20 mL) and water (10 mL). The organic layer was concentrated under reduced pressure and the resulting residue was purified by silica-gel column chromatography eluting with 20:1 dichloromethane/methanol to afford 311a (120 mg, 32%) as a brown solid. MS-ESI: [M+H]+ 583.2.

후처리

  1. customA 25-mL single-neck round-bottomed flask equipped with a magnetic stirrer and a reflux condenser
  2. customAfter bubbling nitrogen through the resulting mixture for 10 minutes
  3. temperatureit was heated
  4. temperatureat reflux for 2 h
  5. customThe mixture was then evaporated under reduced pressure
  6. customthe residue was partitioned between ethyl acetate (20 mL) and water (10 mL)
  7. concentrationThe organic layer was concentrated under reduced pressure
  8. customthe resulting residue was purified by silica-gel column chromatography
  9. washeluting with 20:1 dichloromethane/methanol

출처 및 근거

ORD 기록
ord-0ff0b29c3798477d8a47bf66e8d8365d
출처 데이터셋
uspto-grants-2014_05
특허 번호
US08716274B2

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