Cesium carbonate → 3-Bromo-5-{4,4-dimethyl-9-oxo-1,10-diazatricyclo[6.4.0.02,6]dodeca-2(6),7-dien-10-yl}pyridine-4-carbaldehyde

HRID 1021614Notes

Reaction equation

HRID 1021614 reaction equation
Br[C:2]1[CH:9]=[N:8][CH:7]=[C:6]([Br:10])[C:3]=1[CH:4]=[O:5].[CH3:11][C:12]1([CH3:25])[CH2:23][C:22]2[CH:21]=[C:20]3[N:15]([CH2:16][CH2:17][NH:18][C:19]3=[O:24])[C:14]=2[CH2:13]1.C(=O)([O-])[O-].[Cs+].[Cs+].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>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>[Br:10][C:6]1[CH:7]=[N:8][CH:9]=[C:2]([N:18]2[CH2:17][CH2:16][N:15]3[C:20](=[CH:21][C:22]4[CH2:23][C:12]([CH3:11])([CH3:25])[CH2:13][C:14]=43)[C:19]2=[O:24])[C:3]=1[CH:4]=[O:5]

Participants

7

Reactant 4

HCID 10796Cesium carbonateHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 27629983,5-Dibromo-4-pyridinecarboxaldehydeHCID 580442027,7-dimethyl-3,4,7,8-tetrahydro-2H-cyclopenta[4,5]pyrrolo[1,2-a]pyrazin-1(6H)-one

Product 1

HCID 866841823-Bromo-5-{4,4-dimethyl-9-oxo-1,10-diazatricyclo[6.4.0.02,6]dodeca-2(6),7-dien-10-yl}pyridine-4-carbaldehydeYield 70%

Reagents, catalysts & solvents 2

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

Conditions

Temperature
100 °C

Procedure

A 100-mL single-neck round-bottomed flask equipped with a magnetic stirrer and reflux condenser was charged with 1,4-dioxane (15 mL), 3,5-dibromoisonicotinaldehyde (400 mg, 1.5 mmol), 107e (155 mg, 0.76 mmol), and cesium carbonate (176 mg, 1.5 mmol). Xantphos (40 mg, 0.08 mmol) and Pd2(dba)3 (70 mg, 0.08 mmol) were added, and the reaction mixture was heated at 100° C. for 5 h. After this time the reaction was cooled to room temperature and filtered. The filtrate was concentrated under reduced pressure. The residue was purified on flash column eluting with DCM:MeOH (20:1) to afford 107f (200 mg, 70%). MS: [M+H]+ 388.

Workup

  1. customA 100-mL single-neck round-bottomed flask equipped with a magnetic stirrer
  2. temperaturereflux condenser
  3. temperatureAfter this time the reaction was cooled to room temperature
  4. filtrationfiltered
  5. concentrationThe filtrate was concentrated under reduced pressure
  6. customThe residue was purified on flash column
  7. washeluting with DCM:MeOH (20:1)

Sources & evidence

ORD record
ord-8c2f180120424093b16b504f08644b64
Source dataset
uspto-grants-2014_05
Patent number
US08716274B2

Reaction notes

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