Cesium carbonate → (R)-tert-Butyl 3-(6-(pyrazolo[1,5-a]pyrazin-3-yl)pyrazin-2-ylamino)piperidine-1-carboxylate

HRID 1500766Notes

Reaction equation

HRID 1500766 reaction equation
[NH2:1][C@@H:2]1[CH2:7][CH2:6][CH2:5][N:4]([C:8]([O:10][C:11]([CH3:14])([CH3:13])[CH3:12])=[O:9])[CH2:3]1.C(=O)([O-])[O-].[Cs+].[Cs+].Cl[C:22]1[N:27]=[C:26]([C:28]2[CH:29]=[N:30][N:31]3[CH:36]=[CH:35][N:34]=[CH:33][C:32]=23)[CH:25]=[N:24][CH:23]=1>CN(C=O)C.CC1(C)C2C=CC=C(P(C3C=CC=CC=3)C3C=CC=CC=3)C=2OC2C1=CC=CC=2P(C1C=CC=CC=1)C1C=CC=CC=1>[N:30]1[N:31]2[CH:36]=[CH:35][N:34]=[CH:33][C:32]2=[C:28]([C:26]2[N:27]=[C:22]([NH:1][C@@H:2]3[CH2:7][CH2:6][CH2:5][N:4]([C:8]([O:10][C:11]([CH3:14])([CH3:13])[CH3:12])=[O:9])[CH2:3]3)[CH:23]=[N:24][CH:25]=2)[CH:29]=1

Participants

6

Reactant 3

HCID 10796Cesium carbonateHCID 1501974tert-butyl (3R)-3-aminopiperidine-1-carboxylateHCID 866917833-(6-Chloropyrazin-2-yl)pyrazolo[1,5-a]pyrazine

Product 1

HCID 86691784(R)-tert-Butyl 3-(6-(pyrazolo[1,5-a]pyrazin-3-yl)pyrazin-2-ylamino)piperidine-1-carboxylateYield 44%

Reagents, catalysts & solvents 2

HCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)CatalystHCID 6228DimethylformamideSolvent

Conditions

Temperature
100 °C

Procedure

Tert-butyl (3R)-3-aminopiperidine-1-carboxylate (0.41 g, 2.05 mmol), tris(dibencylidenoacetone)dipalladium(0) (0.034 g, 0.037 mmol), 9,9-dimethyl-4,5-bis(diphenylphosphino) xanthene (0.043 g, 0.074 mmol) and cesium carbonate (0.848 g, 2.6 mmol) were added to a suspension of 3-(6-chloropyrazin-2-yl)pyrazolo[1,5-a]pyrazine (Preparation 29b, 0.43 g, 1.86 mmol)) in N,N′-dimethylformamide (10 mL) and the resulting mixture was purged with argon before being heated to 100° C. for 7 h. After cooling to ambient temperature, the reaction mixture was filtered though Celite®, eluting with methanol. The filtrate was evaporated and the residue was purified by flash chromatography (7:3 ethyl acetate/hexane to 100% ethyl acetate) to yield the title compound (0.320 g, 44%) as a greenish solid.

Workup

  1. customthe resulting mixture was purged with argon
  2. temperatureAfter cooling to ambient temperature
  3. filtrationthe reaction mixture was filtered though Celite®
  4. washeluting with methanol
  5. customThe filtrate was evaporated
  6. customthe residue was purified by flash chromatography (7:3 ethyl acetate/hexane to 100% ethyl acetate)

Sources & evidence

ORD record
ord-895bafa756ed4b4a8de4173afd9b6b1c
Source dataset
uspto-grants-2015_12
Patent number
US09206183B2

Reaction notes

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