Potassium Carbonate → HCID 53731419, compound

HRID 1978644Notes

Reaction equation

HRID 1978644 reaction equation
Br[C:2]1[CH:3]=[CH:4][C:5]2[S:11](=[O:13])(=[O:12])[CH2:10][CH2:9][C:8]([C:14]([NH:16]C3C=CC(CN(C)C4CCOCC4)=CC=3)=[O:15])=[CH:7][C:6]=2[CH:32]=1.B([O-])([O-])OC1C=CC(N2CCOCC2)=C(F)C=1.C(=O)([O-])[O-].[K+].[K+]>C1(C)C=CC=CC=1.C(O)C.O.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>[O:12]=[S:11]1(=[O:13])[C:5]2[CH:4]=[CH:3][CH:2]=[CH:32][C:6]=2[CH:7]=[C:8]([C:14]([NH2:16])=[O:15])[CH2:9][CH2:10]1

Participants

6

Reactant 3

HCID 11430Potassium CarbonateHCID 219957067-bromo-N-[4-[[N-methyl-N-(tetrahydropyran-4-yl)amino]methyl]phenyl]-1,1-dioxo-2,3-dihydro-1-benzothiepine-4-carboxamideHCID 86756790HCID 86756790, compound

Product 1

HCID 53731419HCID 53731419, compoundYield 108.7%

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 86587398Ethanol toluene waterSolvent

Procedure

Under argon atmosphere, a mixture of 7-bromo-N-[4-[[N-methyl-N-(tetrahydropyran-4-yl)amino]methyl]phenyl]-1,1-dioxo-2,3-dihydro-1-benzothiepine-4-carboxamide (300 mg), 3-fluoro-4-morpholinophenyl borate (156 mg) and potassium carbonate (160 mg) in toluene/ethanol/water (10/1/1 ml) was stirred at room temperature for 1 hour. To the mixture was added tetrakistriphenylphosphinepalladium (33 mg), and the. mixture was refluxed for 6 hours, cooled, extracted with ethyl acetate and washed with saturated brine. The extract was heated at 70° C., and crystals were dissolved. The solution was dried with magnesium sulfate and concentrated under reduced pressure to give crystals, which were collected by filtration and recrystallized from ethanol to give yellow crystals of 7-(3-fluoro-4-morpholinophenyl)-N-[4-[N-methyl-N-(tetrahydropyran-4-yl)amino]methyl]phenyl]-1,1-dioxo-2,3-dihydro-1-benzothiepine-4-carboxamide (Compound 61) (149 mg).

Workup

  1. temperaturemixture was refluxed for 6 hours
  2. temperaturecooled
  3. extractionextracted with ethyl acetate
  4. washwashed with saturated brine
  5. temperatureThe extract was heated at 70° C.
  6. dissolutioncrystals were dissolved
  7. dry with materialThe solution was dried with magnesium sulfate
  8. concentrationconcentrated under reduced pressure
  9. customto give crystals, which
  10. filtrationwere collected by filtration
  11. customrecrystallized from ethanol

Sources & evidence

ORD record
ord-8dd175d5edf74efeb4ab0503aa71e28a
Source dataset
uspto-grants-2001_05
Patent number
US06235771B1

Reaction notes

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