Potassium Carbonate → 9-{[2-Methyl-4-(trifluoromethyl)phenyl]sulfonyl}-8,9,10,10a-tetrahydropyrido[2',3':3,4]pyrrolo[1,2-a]pyrazin-5(7H)-one

HRID 1427166Notes

Reaction equation

HRID 1427166 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]=[CH:26][CH:25]=[N: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]=[CH:26][CH:25]=[N:24][C:23]=3[CH:17]2[CH2:16]1)(=[O:14])=[O:13]

Participants

5

Reactant 3

HCID 11430Potassium CarbonateHCID 574072TrimethylboroxineHCID 705582489-{[2-Bromo-4-(trifluoromethyl)phenyl]sulfonyl}-8,9,10,10a-tetrahydropyrido[2',3':3,4]pyrrolo[1,2-a]pyrazin-5(7H)-one2×

Product 1

HCID 705590619-{[2-Methyl-4-(trifluoromethyl)phenyl]sulfonyl}-8,9,10,10a-tetrahydropyrido[2',3':3,4]pyrrolo[1,2-a]pyrazin-5(7H)-oneYield 55.9%

Reagents, catalysts & solvents 1

HCID 178418397HCID 178418397, compoundCatalyst

Conditions

Temperature
90 °C

Procedure

A mixture of 9-{[2-bromo-4-(trifluoromethyl)phenyl]sulfonyl}-8,9,10,10a-tetrahydropyrido[2′,3′:3,4]pyrrolo[1,2-a]pyrazin-5(7H)-one (265 mg; may be prepared as described in Intermediate 24), trimethylboroxin (182 mg), potassium carbonate (200 mg) and Pd(PPh3)4 (109 mg) was heated to 90° C. under argon for 6 hours. The reaction mixture was partitioned between EtOAc and saturated sodium bicarbonate solution, and then the aqueous was re-extracted with EtOAc. The combined organic phases were washed with brine, dried through a hydrophobic frit and evaporated to a brown oil (335 mg). The residue was purified by chromatography eluting with 0-90% ethyl acetate in iso-hexane over 12 column volumes. The desired fractions were combined and evaporated to give the title compound as a pale yellow crystalline solid (128 mg).

Workup

  1. customThe reaction mixture was partitioned between EtOAc and saturated sodium bicarbonate solution
  2. extractionthe aqueous 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 (335 mg)
  6. customThe residue was purified by chromatography
  7. washeluting with 0-90% ethyl acetate in iso-hexane over 12 column volumes
  8. customevaporated

Sources & evidence

ORD record
ord-1918919af6e840c79144be78d21b8fc1
Source dataset
uspto-grants-2015_01
Patent number
US08933132B2

Reaction notes

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