Cesium carbonate → 3-Bromo-5-{4,4-dimethyl-9-oxo-7-thia-10-azatricyclo[6.4.0.02,6]dodeca-1(8), 2(6)-dien-10-yl}pyridine-4-carbaldehyde

HRID 1021606Notes

Reaction equation

HRID 1021606 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])[CH2:24][C:15]2[C:16]3[CH2:21][CH2:20][NH:19][C:18](=[O:22])[C:17]=3[S:23][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:19]2[CH2:20][CH2:21][C:16]3[C:15]4[CH2:24][C:12]([CH3:11])([CH3:25])[CH2:13][C:14]=4[S:23][C:17]=3[C:18]2=[O:22])[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 580438956,6-Dimethyl-2,3,4,5,6,7-hexahydro-1H-cyclopenta[4,5]thieno[2,3-c]pyridin-1-one

Product 1

HCID 866841773-Bromo-5-{4,4-dimethyl-9-oxo-7-thia-10-azatricyclo[6.4.0.02,6]dodeca-1(8), 2(6)-dien-10-yl}pyridine-4-carbaldehydeYield 65%

Reagents, catalysts & solvents 2

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

Conditions

Temperature
100 °C

Procedure

To 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-dibromoisonicotin-aldehyde (400 mg, 1.5 mmol), 4,4-dimethyl-7-thia-10-azatricyclo[6.4.0.02,6]dodeca-1(8),2(6)-dien-9-one (106h) (170 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 and the residue was purified on flash column eluting with DCM:MeOH (20:1) to afford 106i (200 mg, 65%). MS: [M+H]+ 405.

Workup

  1. customTo a 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-db17b6ec274f464e8a232ac4876634e7
Source dataset
uspto-grants-2014_05
Patent number
US08716274B2

Reaction notes

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