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

HRID 593059Notes

Reaction equation

HRID 593059 reaction equation
[O:1]1[CH2:4][CH:3]([N:5]2[CH:9]=[C:8]([NH2:10])[N:7]=[CH:6]2)[CH2:2]1.[C:11]([O:14][CH2:15][C:16]1[C:17]([N:31]2[CH2:42][CH2:41][N:40]3[C:33](=[CH:34][C:35]4[CH2:36][C:37]([CH3:44])([CH3:43])[CH2:38][C:39]=43)[C:32]2=[O:45])=[N:18][CH:19]=[CH:20][C:21]=1[C:22]1[CH:27]=[C:26](Br)[C:25](=[O:29])[N:24]([CH3:30])[CH:23]=1)(=[O:13])[CH3:12].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:11]([O:14][CH2:15][C:16]1[C:17]([N:31]2[CH2:42][CH2:41][N:40]3[C:33](=[CH:34][C:35]4[CH2:36][C:37]([CH3:44])([CH3:43])[CH2:38][C:39]=43)[C:32]2=[O:45])=[N:18][CH:19]=[CH:20][C:21]=1[C:22]1[CH:27]=[C:26]([NH:10][C:8]2[N:7]=[CH:6][N:5]([CH:3]3[CH2:4][O:1][CH2:2]3)[CH:9]=2)[C:25](=[O:29])[N:24]([CH3:30])[CH:23]=1)(=[O:13])[CH3:12]

Participants

7

Reactant 4

HCID 10796Cesium carbonateHCID 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 AcetateHCID 866845201-(Oxetan-3-yl)-1H-imidazol-4-amine

Product 1

HCID 86684521(2-{4,4-Dimethyl-9-oxo-1,10-diazatricyclo[6.4.0.02,6]dodeca-2(6),7-dien-10-yl}-4-(1-methyl-5-{[1-(oxetan-3-yl)-1H-imidazol-4-yl]amino}-6-oxo-1,6-dihydropyridin-3-yl)pyridin-3-yl)methyl AcetateYield 47.8%

Reagents, catalysts & solvents 2

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

Conditions

Temperature
100 °C

Procedure

A 25-mL round-bottomed flask equipped with a magnetic stirrer and a reflux condenser was charged with 285b (40 mg, 0.28 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 (150 mg, 0.28 mmol), Pd2(dba)3 (15 mg, 0.015 mmol), XantPhos (18 mg, 0.03 mmol), cesium carbonate (200 mg, 0.6 mmol), and 1,4-dioxane (6 mL). After three cycles of vacuum/argon flush, the mixture was heated at 100° C. for 2 h. It was then cooled to room temperature and filtered. The filtrate was concentrated under reduced pressure and the residue was purified by silica-gel column chromatography eluting with 25:1 dichloromethane/methanol to afford 285c as a yellow solid (80 mg, 47%). MS-ESI: [M+H]+ 598.3.

Workup

  1. customA 25-mL round-bottomed flask equipped with a magnetic stirrer and a reflux condenser
  2. customAfter three cycles of vacuum/argon flush
  3. temperatureIt was then cooled to room temperature
  4. filtrationfiltered
  5. concentrationThe filtrate was concentrated under reduced pressure
  6. customthe residue was purified by silica-gel column chromatography
  7. washeluting with 25:1 dichloromethane/methanol

Sources & evidence

ORD record
ord-447d6ce397ff4b9d998b757d3755baf9
Source dataset
uspto-grants-2016_01
Patent number
US09238655B2

Reaction notes

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