Potassium Carbonate → 2-{[2-Methyl-4-(trifluoromethyl)phenyl]sulfonyl}-1,3,4,10b-tetrahydropyrido[4',3':3,4]pyrrolo[1,2-a]pyrazin-6(2H)-one

HRID 1427167Notes

Reaction equation

HRID 1427167 reaction equation
Br[C:2]1[CH:7]=[C:6]([C:8]([F:11])([F:10])[F:9])[CH:5]=[CH:4][C:3]=1[S:12]([N:15]1[CH2:20][CH2:19][N:18]2[C:21](=[O:28])[C:22]3[CH:27]=[N:26][CH:25]=[CH:24][C:23]=3[CH:17]2[CH2:16]1)(=[O:14])=[O:13].[CH3:29]B1OB(C)OB(C)O1.C(=O)([O-])[O-].[K+].[K+]>C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[CH3:29][C:2]1[CH:7]=[C:6]([C:8]([F:11])([F:10])[F:9])[CH:5]=[CH:4][C:3]=1[S:12]([N:15]1[CH2:20][CH2:19][N:18]2[C:21](=[O:28])[C:22]3[CH:27]=[N:26][CH:25]=[CH:24][C:23]=3[CH:17]2[CH2:16]1)(=[O:14])=[O:13]

Participants

5

Reactant 3

HCID 11430Potassium CarbonateHCID 574072TrimethylboroxineHCID 705577642-{[2-Bromo-4-(trifluoromethyl)phenyl]sulfonyl}-1,3,4,10b-tetrahydropyrido[4',3':3,4]pyrrolo[1,2-a]pyrazin-6(2H)-one

Product 1

HCID 575245122-{[2-Methyl-4-(trifluoromethyl)phenyl]sulfonyl}-1,3,4,10b-tetrahydropyrido[4',3':3,4]pyrrolo[1,2-a]pyrazin-6(2H)-one

Reagents, catalysts & solvents 1

HCID 178418397HCID 178418397, compoundCatalyst

Conditions

Temperature
90 °C

Procedure

A mixture of 2-{[2-bromo-4-(trifluoromethyl)phenyl]sulfonyl}-1,3,4,10b-tetrahydropyrido[4′,3′:3,4]pyrrolo[1,2-a]pyrazin-6(2H)-one (250 mg), trimethylboroxin (0.190 mL), potassium carbonate (189 mg) and Pd(PPh3)4 (103 mg) was heated to 90° C. under argon for 18 hours. The reaction mixture was partitioned between EtOAc and aqueous saturated sodium bicarbonate solution. The aqueous phase was re-extracted with EtOAc. The combined organic phases were washed with brine, dried through a hydrophobic frit and evaporated to a brown oil. This was purified by chromatography eluting with 0-5% methanol in DCM over 12 column volumes. The clean fractions were combined and evaporated to a pale yellow gum. This was purified further to remove triphenylphosphine oxide by MDAP. The clean fraction was evaporated to give the title compound as a white solid (46 mg).

Workup

  1. customThe reaction mixture was partitioned between EtOAc and aqueous saturated sodium bicarbonate solution
  2. extractionThe aqueous phase was re-extracted with EtOAc
  3. washThe combined organic phases were washed with brine
  4. customdried through a hydrophobic frit
  5. customevaporated to a brown oil
  6. customThis was purified by chromatography
  7. washeluting with 0-5% methanol in DCM over 12 column volumes
  8. customevaporated to a pale yellow gum
  9. customThis was purified further
  10. customto remove triphenylphosphine oxide by MDAP
  11. customThe clean fraction was evaporated

Sources & evidence

ORD record
ord-0bdb368ab3574bf0931f591299417d25
Source dataset
uspto-grants-2015_01
Patent number
US08933132B2

Reaction notes

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