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

HRID 1185142Notes

Reaction equation

HRID 1185142 reaction equation
[F:1][C:2]([F:15])([F:14])[CH2:3][N:4]1[CH2:9][CH2:8][N:7]2[N:10]=[C:11]([NH2:13])[CH:12]=[C:6]2[CH2:5]1.Br[C:17]1[C:18](=[O:25])[N:19]([CH3:24])[CH:20]=[C:21]([Br:23])[CH:22]=1.C(=O)([O-])[O-].[Cs+].[Cs+].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>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].O1CCOCC1>[Br:23][C:21]1[CH:22]=[C:17]([NH:13][C:11]2[CH:12]=[C:6]3[CH2:5][N:4]([CH2:3][C:2]([F:1])([F:14])[F:15])[CH2:9][CH2:8][N:7]3[N:10]=2)[C:18](=[O:25])[N:19]([CH3:24])[CH:20]=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 866839975-(2,2,2-Trifluoroethyl)-4,5,6,7-tetrahydropyrazolo[1,5-a]pyrazin-2-amine

Product 1

HCID 866839985-Bromo-1-methyl-3-(5-(2,2,2-trifluoroethyl)-4,5,6,7-tetrahydropyrazolo[1,5-a]pyrazin-2-ylamino)pyridin-2(1H)-oneYield 76%

Reagents, catalysts & solvents 2

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

Procedure

A 100-mL round-bottomed flask equipped with a reflux condenser was charged with 134b (300 mg, 1.36 mmol), 3,5-dibromo-1-methylpyridin-2(1H)-one (364 mg, 1.36 mmol), cesium carbonate (887 mg, 2.7 mmol), and 1,4-dioxane (20 mL). After bubbling nitrogen through the suspension for 10 minutes, xantphos (78 mg, 0.136 mmol) and Pd2(dba)3 (62 mg, 0.068 mmol) were added. The system was subjected to three cycles of vacuum/argon flush and heated at reflux for 5 h. It was then cooled to room temperature and filtered. The solid was washed with dichloromethane (30 mL). The combined filtrate was concentrated under reduced pressure. The solid residue was purified by silica-gel column chromatography eluting with dichloromethane/methanol (80/1 to 30/1) to afford 134c (420 mg, 76%) as a yellow solid. MS-ESI: [M+H]+ 406.0

Workup

  1. customA 100-mL round-bottomed flask equipped with a reflux condenser
  2. customAfter bubbling nitrogen through the suspension for 10 minutes
  3. customflush
  4. temperatureheated
  5. temperatureat reflux for 5 h
  6. filtrationfiltered
  7. washThe solid was washed with dichloromethane (30 mL)
  8. concentrationThe combined filtrate was concentrated under reduced pressure
  9. customThe solid residue was purified by silica-gel column chromatography
  10. washeluting with dichloromethane/methanol (80/1 to 30/1)

Sources & evidence

ORD record
ord-0367599488994d13be4d866f1fcb280f
Source dataset
uspto-grants-2014_03
Patent number
US08669251B2

Reaction notes

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