Cesium carbonate → 1-(1-methyl-1H-indazol-5-yl)tetrahydropyrimidin-2(1H)-one

HRID 879326Notes

Reaction equation

HRID 879326 reaction equation
Br[C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[N:7]([CH3:11])[N:6]=[CH:5]2.[NH:12]1[CH2:17][CH2:16][CH2:15][NH:14][C:13]1=[O:18].C1(P(C2C=CC=CC=2)C2C3OC4C(=CC=CC=4P(C4C=CC=CC=4)C4C=CC=CC=4)C(C)(C)C=3C=CC=2)C=CC=CC=1.C(=O)([O-])[O-].[Cs+].[Cs+]>O1CCOCC1.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]>[CH3:11][N:7]1[C:8]2[C:4](=[CH:3][C:2]([N:12]3[CH2:17][CH2:16][CH2:15][NH:14][C:13]3=[O:18])=[CH:10][CH:9]=2)[CH:5]=[N:6]1

Participants

7

Reactant 4

HCID 10796Cesium carbonateHCID 746152(1H)-Pyrimidinone, tetrahydro-HCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 225587255-Bromo-1-methyl-1H-indazole

Product 1

HCID 866998431-(1-methyl-1H-indazol-5-yl)tetrahydropyrimidin-2(1H)-one

Reagents, catalysts & solvents 2

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

Conditions

Temperature
100 °C

Procedure

To a solution of 5-bromo-1-methyl-1H-indazole (76 mg, 0.36 mmol) in 1,4-dioxane (5 mL) was added tetrahydropyrimidin-2(1H)-one (Aldrich, 216 mg, 2.16 mmol), followed by Pd2(dba)3 (16 mg, 0.02 mmol), 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene (31 mg, 0.06 mmol) and cesium carbonate (176 mg, 0.54 mmol). The reaction mixture was degassed with nitrogen and heated at 100° C. for 16 hours. The mixture was diluted with ethyl acetate, washed with water and brine, and dried over Na2SO4 and filtered. Concentration and purification by flash column chromatography (hexanes/EtOAc) yielded 1-(1-methyl-1H-indazol-5-yl)tetrahydropyrimidin-2(1H)-one. LCMS-ESI+: calc'd for C12H14N4O: 231.2 (M+H+); Found: 231.2 (M+H+).

Workup

  1. customThe reaction mixture was degassed with nitrogen
  2. additionThe mixture was diluted with ethyl acetate
  3. washwashed with water and brine
  4. dry with materialdried over Na2SO4
  5. filtrationfiltered
  6. concentrationConcentration and purification by flash column chromatography (hexanes/EtOAc)

Sources & evidence

ORD record
ord-dab7172ec3da4334b126329b09f75056
Source dataset
uspto-grants-2015_03
Patent number
US08987250B2

Reaction notes

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