Cesium carbonate → HCID 57495314, compound

HRID 242311Notes

Reaction equation

HRID 242311 reaction equation
[CH3:1][O:2][C:3]1[C:4]2[CH2:12][NH:11][CH2:10][CH2:9][C:5]=2[N:6]=[CH:7][N:8]=1.Br[C:14]1[CH:15]=[C:16]([CH3:22])[C:17]([O:20][CH3:21])=[N:18][CH:19]=1.C(=O)([O-])[O-].[Cs+].[Cs+].CC(C1C=C(C(C)C)C(C2C=CC=CC=2P(C2CCCCC2)C2CCCCC2)=C(C(C)C)C=1)C>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].CCOC(C)=O.CO.O1CCOCC1>[CH3:1][O:2][C:3]1[C:4]2[CH2:12][N:11]([C:14]3[CH:19]=[N:18][C:17]([O:20][CH3:21])=[C:16]([CH3:22])[CH:15]=3)[CH2:10][CH2:9][C:5]=2[N:6]=[CH:7][N:8]=1

Participants

8

Reactant 4

HCID 10796Cesium carbonateHCID 111557942-Dicyclohexylphosphino-2',4',6'-triisoprophylbiphenylHCID 225911765-Bromo-2-methoxy-3-methylpyridineHCID 509892144-methoxy-5H,6H,7H,8H-pyrido[4,3-d]pyrimidine

Product 1

HCID 57495314HCID 57495314, compoundYield 36.4%

Reagents, catalysts & solvents 3

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 312751,4-DioxaneSolventHCID 21584119Ethylacetate methanolSolvent

Conditions

Temperature
110 °C

Procedure

To a glass vial was added 4-methoxy-5,6,7,8-tetrahydro-pyrido[4,3-d]pyrimidine (WO 2008/130481, p 47) (0.570 g, 3.45 mmol), 5-bromo-2-methoxy-3-methylpyridine (0.697 g, 3.45 mmol), cesium carbonate (2.25 g, 6.90 mmol), tris(dibenzylideneacetone)dipalladium(0) (0.316 g, 0.345 mmol), X-Phos (0.493 g, 1.04 mmol) and anhydrous dioxane (5 mL). The vial was flushed with a stream of argon for 15 sec and capped. The mixture was heated with stirring for 1 h 45 min at 110° C. then allowed to cool to room temperature and stirred at RT for 3 days. The reaction mixture was filtered through a celite pad and concentrated in vacuo. Purified by flash chromatography on silica gel with heptane/EtOAc, 100/0 to 0/100 then EtOAc/MeOH, 90/10 to give 4-methoxy-6-(6-methoxy-5-methyl-pyridin-3-yl)-5,6,7,8-tetrahydro-pyrido[4,3-d]pyrimidine as a brown gum (0.36 g, 36% yield) LCMS: [M+H]+=287.0, Rt(7)=0.80 min.

Workup

  1. customThe vial was flushed with a stream of argon for 15 sec
  2. customcapped
  3. temperatureThe mixture was heated
  4. temperatureto cool to room temperature
  5. stirringstirred at RT for 3 days
  6. filtrationThe reaction mixture was filtered through a celite pad
  7. concentrationconcentrated in vacuo
  8. customPurified by flash chromatography on silica gel with heptane/EtOAc, 100/0 to 0/100

Sources & evidence

ORD record
ord-24d52821a6014d77865f3afc2252d318
Source dataset
uspto-grants-2014_02
Patent number
US08653092B2

Reaction notes

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