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

HRID 510313Notes

Reaction equation

HRID 510313 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-53a4543df3354abd8becec8e4eb9c27c
Source dataset
uspto-grants-2015_08
Patent number
US09096586B2

Reaction notes

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