Cesium carbonate → 5-Bromo-3-(5-cyclopropyl-4,5,6,7-tetrahydropyrazolo[1,5-a]pyrazin-2-ylamino)-1-methylpyridin-2(1H)-one

HRID 1918867Notes

Reaction equation

HRID 1918867 reaction equation
[CH:1]1([N:4]2[CH2:9][CH2:8][N:7]3[N:10]=[C:11]([NH2:13])[CH:12]=[C:6]3[CH2:5]2)[CH2:3][CH2:2]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.Br[C:57]1[C:58](=[O:65])[N:59]([CH3:64])[CH:60]=[C:61]([Br:63])[CH:62]=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]>[Br:63][C:61]1[CH:62]=[C:57]([NH:13][C:11]2[CH:12]=[C:6]3[CH2:5][N:4]([CH:1]4[CH2:3][CH2:2]4)[CH2:9][CH2:8][N:7]3[N:10]=2)[C:58](=[O:65])[N:59]([CH3:64])[CH:60]=1

Participants

7

Reactant 4

HCID 10796Cesium carbonateHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 36143503,5-Dibromo-1-methylpyridin-2(1H)-oneHCID 580439305-Cyclopropyl-4,5,6,7-tetrahydropyrazolo[1,5-a]pyrazin-2-amine

Product 1

HCID 580436915-Bromo-3-(5-cyclopropyl-4,5,6,7-tetrahydropyrazolo[1,5-a]pyrazin-2-ylamino)-1-methylpyridin-2(1H)-oneYield 35.5%

Reagents, catalysts & solvents 2

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

Procedure

A mixture of 5-cyclopropyl-4,5,6,7-tetrahydropyrazolo[1,5-a]pyrazin-2-amine 135b (1.39 g, 7.8 mmol), XantPhos (450 mg, 0.78 mmol), Pd2 dba3 (476 mg, 0.52 mmol), 3,5-dibromo-1-methylpyridin-2(1H)-one (1.72 g, 6.5 mmol) and Cs2CO3 (6.3 mg. 19.5 mmol) in 1,4-dioxane (30 mL) was heated at reflux for 1 h. After the completion of the reaction the mixture was filtered off and the solid was washed with methanol (60 mL). The filtrate was evaporated in vacuo and the residue was purified on reverse phase Combi-flash to give 135c (0.84 g, 30%). MS: [M+H]+ 364.

Workup

  1. temperaturewas heated
  2. temperatureat reflux for 1 h
  3. customAfter the completion of the reaction the mixture
  4. filtrationwas filtered off
  5. washthe solid was washed with methanol (60 mL)
  6. customThe filtrate was evaporated in vacuo
  7. customthe residue was purified on reverse phase Combi-flash

Sources & evidence

ORD record
ord-7c21aea6fb524ff7a4f58b980878d4bf
Source dataset
uspto-grants-2013_12
Patent number
US08618107B2

Reaction notes

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