Cesium carbonate → 2-(5-Bromo-1-methyl-2-oxo-1,2-dihydropyridin-3-ylamino)-5-isopropyl-4,5-dihydropyrazolo[1,5-a]pyrazin-6(7H)-one

HRID 407796Notes

Reaction equation

HRID 407796 reaction equation
[NH2:1][C:2]1[CH:14]=[C:5]2[CH2:6][N:7]([CH:11]([CH3:13])[CH3:12])[C:8](=[O:10])[CH2:9][N:4]2[N:3]=1.Br[C:16]1[C:17](=[O:24])[N:18]([CH3:23])[CH:19]=[C:20]([Br:22])[CH:21]=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].O1CCOCC1>[Br:22][C:20]1[CH:21]=[C:16]([NH:1][C:2]2[CH:14]=[C:5]3[CH2:6][N:7]([CH:11]([CH3:12])[CH3:13])[C:8](=[O:10])[CH2:9][N:4]3[N:3]=2)[C:17](=[O:24])[N:18]([CH3:23])[CH:19]=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 866840562-Amino-5-isopropyl-4,5-dihydropyrazolo[1,5-a]pyrazin-6(7H)-one

Product 1

HCID 866840572-(5-Bromo-1-methyl-2-oxo-1,2-dihydropyridin-3-ylamino)-5-isopropyl-4,5-dihydropyrazolo[1,5-a]pyrazin-6(7H)-oneYield 79%

Reagents, catalysts & solvents 2

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

Conditions

Temperature
100 °C

Procedure

A 100-mL round-bottomed flask equipped with a reflux condenser was charged with 151e (200 mg, 1.0 mmol), 3,5-dibromo-1-methylpyridin-2(1H)-one (268 mg, 1.0 mmol), Pd2(dba)3 (50 mg, 0.050 mmol), xantphos (58 mg, 0.10 mmol), Cs2CO3 (652 mg, 2.0 mmol) and 1,4-dioxane (20 mL). The system was subjected to three cycles of vacuum/argon flush and heated at 100° C. for 2 h. It was then cooled to room temperature and filtered. The solid was washed with dichloromethane (2×10 mL). The combined filtrate was concentrated under reduced pressure. The residue was purified by silica-gel column chromatography eluting with dichloromethane/methanol (80:1 to 30:1) to afford 151f (300 mg, 79%) as a yellow solid. MS-ESI: [M+H]+ 380.2

Workup

  1. customA 100-mL round-bottomed flask equipped with a reflux condenser
  2. customflush
  3. temperatureIt was then cooled to room temperature
  4. filtrationfiltered
  5. washThe solid was washed with dichloromethane (2×10 mL)
  6. concentrationThe combined filtrate was concentrated under reduced pressure
  7. customThe residue was purified by silica-gel column chromatography
  8. washeluting with dichloromethane/methanol (80:1 to 30:1)

Sources & evidence

ORD record
ord-545e3903b91245a7b623fbea368d668e
Source dataset
uspto-grants-2014_06
Patent number
US08754077B2

Reaction notes

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