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

HRID 593115Notes

Reaction equation

HRID 593115 reaction equation
Br[C:2]1[C:3](=[O:10])[N:4]([CH3:9])[CH:5]=[C:6]([Br:8])[CH:7]=1.[CH3:11][O:12][CH2:13][CH2:14][CH2:15][N:16]1[CH2:21][CH2:20][N:19]2[N:22]=[C:23]([NH2:25])[CH:24]=[C:18]2[CH2:17]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+]>[Pd].[Pd].C(=CC(C=CC1C=CC=CC=1)=O)C1C=CC=CC=1.C(=CC(C=CC1C=CC=CC=1)=O)C1C=CC=CC=1.C(=CC(C=CC1C=CC=CC=1)=O)C1C=CC=CC=1.O1CCOCC1>[Br:8][C:6]1[CH:7]=[C:2]([NH:25][C:23]2[CH:24]=[C:18]3[CH2:17][N:16]([CH2:15][CH2:14][CH2:13][O:12][CH3:11])[CH2:21][CH2:20][N:19]3[N:22]=2)[C:3](=[O:10])[N:4]([CH3:9])[CH:5]=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 866845575-(3-Methoxypropyl)-4,5,6,7-tetrahydropyrazolo[1,5-a]pyrazin-2-amine

Product 1

HCID 866845585-Bromo-3-(5-(3-methoxypropyl)-4,5,6,7-tetrahydropyrazolo[1,5-a]pyrazin-2-yl-amino)-1-methylpyridin-2(1H)-oneYield 42.1%

Reagents, catalysts & solvents 2

HCID 9832798Tris(dibenzylideneacetone) dipalladiumCatalystHCID 312751,4-DioxaneSolvent

Conditions

Temperature
100 °C

Procedure

A 100-mL single-neck round-bottomed flask equipped with a magnetic stirrer and a reflux condenser was charged with 3,5-dibromo-1-methylpyridin-2(1H)-one (320 mg, 1.2 mmol), 309b (250 mg, 1.2 mmol), tris(dibenzylideneacetone) dipalladium(0) (55 mg, 0.060 mmol), xantphos (70 mg, 0.12 mmol), cesium carbonate (782 mg, 2.4 mmol), and 1,4-dioxane (20 mL). The system was subjected to three cycles of vacuum/argon flush and heated at 100° C. for 5 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 309c (200 mg, 42%) as yellow solid. MS-ESI: [M+H]+ 396.2

Workup

  1. customA 100-mL single-neck round-bottomed flask equipped with a magnetic stirrer and 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-00017cc0df5e45b7b9d9e6a65ddaa270
Source dataset
uspto-grants-2016_01
Patent number
US09238655B2

Reaction notes

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