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-[(5-ethyl-1,2-oxazol-3-yl)amino]-1-methyl-6-oxo-1,6-dihydropyridin-3-yl}pyridin-3-yl)methyl Acetate

HRID 1022152Notes

Reaction equation

HRID 1022152 reaction equation
[CH2:1]([C:3]1[O:7][N:6]=[C:5]([NH2:8])[CH:4]=1)[CH3:2].[C:9]([O:12][CH2:13][C:14]1[C:15]([N:29]2[CH2:40][CH2:39][N:38]3[C:31](=[CH:32][C:33]4[CH2:34][C:35]([CH3:42])([CH3:41])[CH2:36][C:37]=43)[C:30]2=[O:43])=[N:16][CH:17]=[CH:18][C:19]=1[C:20]1[CH:25]=[C:24](Br)[C:23](=[O:27])[N:22]([CH3:28])[CH:21]=1)(=[O:11])[CH3:10].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([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:9]([O:12][CH2:13][C:14]1[C:15]([N:29]2[CH2:40][CH2:39][N:38]3[C:31](=[CH:32][C:33]4[CH2:34][C:35]([CH3:42])([CH3:41])[CH2:36][C:37]=43)[C:30]2=[O:43])=[N:16][CH:17]=[CH:18][C:19]=1[C:20]1[CH:25]=[C:24]([NH:8][C:5]2[CH:4]=[C:3]([CH2:1][CH3:2])[O:7][N:6]=2)[C:23](=[O:27])[N:22]([CH3:28])[CH:21]=1)(=[O:11])[CH3:10]

Participants

7

Reactant 4

HCID 10796Cesium carbonateHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 50943815-Ethyl-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 86684539(2-{4,4-Dimethyl-9-oxo-1,10-diazatricyclo[6.4.0.02,6]dodeca-2(6),7-dien-10-yl}-4-{5-[(5-ethyl-1,2-oxazol-3-yl)amino]-1-methyl-6-oxo-1,6-dihydropyridin-3-yl}pyridin-3-yl)methyl AcetateYield 49.5%

Reagents, catalysts & solvents 2

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

Conditions

Temperature
100 °C

Procedure

A 25-mL single-neck round-bottomed flask equipped with a magnetic stirrer and a reflux condenser was charged with 295a (24.8 mg, 0.222 mmol), [4-(5-bromo-1-methyl-6-oxo-1,6-dihydropyridin-3-yl)-2-{4,4-dimethyl-9-oxo-1,10-diazatri-cyclo[6.4.0.02,6]dodeca-2(6),7-dien-10-yl}pyridin-3-yl]methyl acetate 273a (100 mg, 0.185 mmol), Pd2(dba)3 (8.5 mg, 0.0093 mmol), Xantphos (10.7 mg, 0.019 mmol), Cs2CO3 (120.6 mg, 0.37 mmol), and dioxane (10 mL). The system was subjected to three cycles of vacuum/nitrogen flush and heated at 100° C. under N2 protection for 3 h. Analysis of the reaction mixture by LCMS showed complete conversion to the desired product. It was cooled to room temperature and filtered. The filtrate was concentrated under reduced pressure. The residue was washed with acetonitrile (0.5 mL) to afford 295b as white solid (52 mg, 49.5%), which was used in the next step without further purification. MS-ESI: [M+H]+ 570.8

Workup

  1. customA 25-mL single-neck round-bottomed flask equipped with a magnetic stirrer and a reflux condenser
  2. customflush
  3. temperatureIt was cooled to room temperature
  4. filtrationfiltered
  5. concentrationThe filtrate was concentrated under reduced pressure
  6. washThe residue was washed with acetonitrile (0.5 mL)

Sources & evidence

ORD record
ord-1f764654b16a4923a1e7b2e427c602dd
Source dataset
uspto-grants-2014_05
Patent number
US08716274B2

Reaction notes

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