Potassium Carbonate → Tert-butyl 4-(4-(5-vinylpyrazin-2-ylamino)phenylsulfonyl)piperazine-1-carboxylate

HRID 2199318Notes

Reaction equation

HRID 2199318 reaction equation
[CH:1]([C:3]1[N:4]=[CH:5][C:6]([NH2:9])=[N:7][CH:8]=1)=[CH2:2].C([O-])([O-])=O.[K+].[K+].N[C:17]1[CH:22]=[CH:21][C:20]([S:23]([N:26]2[CH2:31][CH2:30][N:29]([C:32]([O:34][C:35]([CH3:38])([CH3:37])[CH3:36])=[O:33])[CH2:28][CH2:27]2)(=[O:25])=[O:24])=[CH:19][CH:18]=1.CC(C1C=C(C(C)C)C(C2C=CC=CC=2P(C2CCCCC2)C2CCCCC2)=C(C(C)C)C=1)C>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]>[CH:1]([C:3]1[N:4]=[CH:5][C:6]([NH:9][C:17]2[CH:18]=[CH:19][C:20]([S:23]([N:26]3[CH2:27][CH2:28][N:29]([C:32]([O:34][C:35]([CH3:38])([CH3:37])[CH3:36])=[O:33])[CH2:30][CH2:31]3)(=[O:25])=[O:24])=[CH:21][CH:22]=2)=[N:7][CH:8]=1)=[CH2:2]

Participants

6

Reactant 4

HCID 11430Potassium CarbonateHCID 10617209tert-Butyl 4-(4-aminophenylsulfonyl)piperazine-1-carboxylateHCID 111557942-Dicyclohexylphosphino-2',4',6'-triisoprophylbiphenylHCID 218972565-Vinylpyrazin-2-amine

Product 1

HCID 67324584Tert-butyl 4-(4-(5-vinylpyrazin-2-ylamino)phenylsulfonyl)piperazine-1-carboxylateYield 65.2%

Reagents, catalysts & solvents 1

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalyst

Conditions

Temperature
100 °C

Procedure

To a solution of 5-vinylpyrazin-2-amine (150 mg, 1.24 mmol) in 2-buOH (4 mL) were added K2CO3 (512 mg, 3.71 mmol), and tert-butyl 4-(4-aminophenylsulfonyl)piperazine-1-carboxylate (421 mg, 1.24 mmol). The reaction mixture was degassed for 10 minutes. To a mixture were added Pd2(dba)3 (76 mg, 0.07 mmol) and X-phos (53 mg, 0.11 mmol). The reaction mixture was heated to 100° C. for 6 hours after which, it was filtered with a pad of celite and partitioned between ethyl acetate and water. The organic layer was separated and the aqueous layer was extracted with ethyl acetate. The combined organic extracts were washed with brine, dried over MgSO4, celite filtered and concentrated under reduced pressure. The crude product was purified by flash chromatography using (20% to 30% Ethyl acetate/Hexane) as a solvent to afford title compound (360 mg, 65% yield). MS m/z: 446 [M+1].

Workup

  1. customThe reaction mixture was degassed for 10 minutes
  2. filtrationwas filtered with a pad of celite
  3. custompartitioned between ethyl acetate and water
  4. customThe organic layer was separated
  5. extractionthe aqueous layer was extracted with ethyl acetate
  6. washThe combined organic extracts were washed with brine
  7. dry with materialdried over MgSO4, celite
  8. filtrationfiltered
  9. concentrationconcentrated under reduced pressure
  10. customThe crude product was purified by flash chromatography

Sources & evidence

ORD record
ord-3c3ad4de72d74a08a3ac14504cfd6454
Source dataset
uspto-grants-2016_06
Patent number
US09358231B2

Reaction notes

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