Cesium carbonate → 5-Bromo-3-(1-cyclopropyl-1H-pyrazol-4-ylamino)-1-methylpyrazin-2(1H)-one

HRID 1918822Notes

Reaction equation

HRID 1918822 reaction equation
[CH:1]1([N:4]2[CH:8]=[C:7]([NH2:9])[CH:6]=[N:5]2)[CH2:3][CH2:2]1.Br[C:11]1[C:12](=[O:19])[N:13]([CH3:18])[CH:14]=[C:15]([Br:17])[N:16]=1.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.C([O-])([O-])=O.[Cs+].[Cs+]>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].C(Cl)Cl.O1CCOCC1>[Br:17][C:15]1[N:16]=[C:11]([NH:9][C:7]2[CH:6]=[N:5][N:4]([CH:1]3[CH2:3][CH2:2]3)[CH:8]=2)[C:12](=[O:19])[N:13]([CH3:18])[CH:14]=1

Participants

8

Reactant 4

HCID 10796Cesium carbonateHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 130629693,5-Dibromo-1-methyl-1H-pyrazin-2-oneHCID 510003781-Cyclopropyl-1H-pyrazol-4-amine

Product 1

HCID 580442185-Bromo-3-(1-cyclopropyl-1H-pyrazol-4-ylamino)-1-methylpyrazin-2(1H)-one

Reagents, catalysts & solvents 3

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 6344DichloromethaneSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
100 °C

Procedure

To a seal tube equipped with a stirring bar, 1-cyclopropyl-1H-pyrazol-4-amine (600 mg, 4.87 mmol), 3,5-dibromo-1-methylpyrazin-2(1H)-one (1.96 g, 7.31 mmol), Pd2(dba)3 (223.1 mg, 0.244 mmol), XantPhos (225.5 mg, 0.390 mmol), Cs2CO3 (5.25 g, 16.08 mmol) and dioxane (12 mL) were added. The tube was sealed and heated at 100° C. overnight. CH2Cl2 (200 mL) was added to the resulting mixture, and the CH2Cl2 solution was washed with water (30 mL×3). The precipitate in the aqueous phase was filtered as pure product 114b. The organic phase was dried over MgSO4, filtered and solvent removed in vacuo. CH2Cl2/ether (1:2, 3 mL) were added to the residue and the mixture was sonicated. The precipitate was filtered, combined with the filtered solids from the aqueous phase, and dried. 5-Bromo-3-(1-cyclopropyl-1H-pyrazol-4-ylamino)-1-methylpyrazin-2(1H)-one 114b was obtained as a yellow solid.

Workup

  1. customTo a seal tube equipped with a stirring bar
  2. customThe tube was sealed
  3. washthe CH2Cl2 solution was washed with water (30 mL×3)
  4. filtrationThe precipitate in the aqueous phase was filtered as pure product 114b
  5. dry with materialThe organic phase was dried over MgSO4
  6. filtrationfiltered
  7. customsolvent removed in vacuo
  8. additionCH2Cl2/ether (1:2, 3 mL) were added to the residue
  9. customthe mixture was sonicated
  10. filtrationThe precipitate was filtered
  11. customdried

Sources & evidence

ORD record
ord-fcbd57cb81a241cab9dd60b564ffe735
Source dataset
uspto-grants-2013_12
Patent number
US08618107B2

Reaction notes

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