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

HRID 593109

Reaction equation

HRID 593109 reaction equation
[CH3:1][O:2][C:3]1[N:8]=[N:7][C:6]([NH2:9])=[CH:5][CH:4]=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[N:7]=[N:8][C:3]([O:2][CH3:1])=[CH:4][CH:5]=2)[C:66](=[O:70])[N:65]([CH3:71])[CH:64]=1)(=[O:54])[CH3:53]

Participants

7

Reactant 4

HCID 10796Cesium carbonateHCID 816736-Methoxypyridazin-3-amineHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 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 86684554(2-{4,4-Dimethyl-9-oxo-1,10-diazatricyclo[6.4.0.02,6]dodeca-2(6),7-dien-10-yl}-4-{5-[(6-methoxypyridazin-3-yl)amino]-1-methyl-6-oxo-1,6-dihydropyridin-3-yl}pyridin-3-yl)methyl AcetateYield 60%

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 6-methoxypyridazin-3-amine (65 mg, 0.52 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 (281 mg, 0.52 mmol), Cs2CO3 (326 mg, 1.0 mmol), and 1,4-dioxane (10 mL). After bubbling nitrogen through the resulting mixture for 20 minutes, it was heated at reflux for 2 h. After the completion of the reaction, the mixture was evaporated under reduced pressure and the residue was partitioned between ethyl acetate (20 mL) and water (10 mL). The ethyl acetate was concentrated under reduced pressure and the residue was purified by silica-gel column chromatography eluting with 20:1 dichloromethane/methanol to afford 306a (180 mg, 60%). MS-ESI: [M+H]+ 584.3.

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 20 minutes
  3. temperatureit was heated
  4. temperatureat reflux for 2 h
  5. customAfter the completion of the reaction
  6. customthe mixture was evaporated under reduced pressure
  7. customthe residue was partitioned between ethyl acetate (20 mL) and water (10 mL)
  8. concentrationThe ethyl acetate was concentrated under reduced pressure
  9. customthe residue was purified by silica-gel column chromatography
  10. washeluting with 20:1 dichloromethane/methanol

Sources & evidence

ORD record
ord-d742d30ab54f408294120297ab2ef76d
Source dataset
uspto-grants-2016_01
Patent number
US09238655B2

Linked notes

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