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 1412059Notes

Reaction equation

HRID 1412059 reaction equation
[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]

Participants

7

Reactant 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

Product 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 AcetateYield 32%

Reagents, catalysts & solvents 2

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 312751,4-DioxaneSolvent

Procedure

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), Pd2 dba3 (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.

Workup

  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

Sources & evidence

ORD record
ord-b94ce496accc4149bdff715f1933865d
Source dataset
uspto-grants-2014_12
Patent number
US08921353B2

Reaction notes

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