Cesium carbonate → 5-Bromo-3-(5-cyclopropyl-4,5,6,7-tetrahydropyrazolo[1,5-a]pyrazin-2-ylamino)-1-methylpyridin-2(1H)-one
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]=1Participants
7
Reactant 4
Product 1
Reagents, catalysts & solvents 2
Procedure
A mixture of 128b (1.39 g, 7.8 mmol), XantPhos (450 mg, 0.78 mmol), Pd2dba3 (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 128c (0.84 g, 30%). MS: [M+H]+ 364.
Workup
- temperaturewas heated
- temperatureat reflux for 1 h
- customAfter the completion of the reaction the mixture
- filtrationwas filtered off
- washthe solid was washed with methanol (60 mL)
- customThe filtrate was evaporated in vacuo
- customthe residue was purified on reverse phase Combi-flash
Sources & evidence
- ORD record
- ord-6f5d1f2520d64029a72bc474ad6734af
- Source dataset
- uspto-grants-2014_05
- Patent number
- US08716274B2
Reaction notes
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