Potassium Carbonate → HCID 21995748, compound

HRID 1978681Notes

Reaction equation

HRID 1978681 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][C:17]3[CH:22]=[CH:21][C:20]([CH2:23][N:24]([CH3:31])[CH:25]4[CH2:30][CH2:29][O:28][CH2:27][CH2:26]4)=[CH:19][CH:18]=3)=[O:15])=[CH:7][C:6]=2[CH:32]=1.C1(C)C=CC=CC=1.C(O)C.O.B([O-])([O-])O[C:46]1[CH:51]=[CH:50][C:49]([O:52][CH2:53][CH3:54])=[C:48]([C:55]#[N:56])[CH:47]=1.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.O>[C:55]([C:48]1[CH:47]=[CH:46][C:51]([C:2]2[CH:3]=[CH:4][C:5]3[S:11](=[O:12])(=[O:13])[CH2:10][CH2:9][C:8]([C:14]([NH:16][C:17]4[CH:22]=[CH:21][C:20]([CH2:23][N:24]([CH3:31])[CH:25]5[CH2:30][CH2:29][O:28][CH2:27][CH2:26]5)=[CH:19][CH:18]=4)=[O:15])=[CH:7][C:6]=3[CH:32]=2)=[CH:50][C:49]=1[O:52][CH2:53][CH3:54])#[N:56]

Participants

7

Reactant 4

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 86587398Ethanol toluene waterHCID 86756812HCID 86756812, compound

Product 1

HCID 21995748HCID 21995748, compoundYield 46.3%

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 962WaterSolvent

Procedure

To 7-bromo-N-[4-[[N-methyl-N-(tetrahydropyran-4-yl)amino]methyl]phenyl]-1,1-dioxo-2,3-dihydro-1-benzothiepine-4-carboxamide (400 mg) was added toluene/ethanol/water (10/1/1, 19.2 ml) and then were added 3-cyano-4-ethoxyphenyl borate (205 mg) and potassium carbonate (251 mg), and the mixture was stirred at room temperature for 30 minutes. To the mixture was added tetrakistriphenylphosphinepalladium (48 mg), and the mixture was refluxed for 18 hours and cooled to room temperature. The mixture was added to water, and the mixture was extracted with ethyl acetate/THF, washed with saturated brine and dried with magnesium sulfate. Under reduced pressure, the solvent was evaporated, and the residue was purified with silica gel column chromatography (ethyl acetate/ethanol=3/1) and recrystallized from ethanol to give 7-(4-cyano-3-ethoxyphenyl)-N-[4-[[N-methyl-N-(tetrahydropyran-4-yl)amino]methyl]phenyl]-1,1-dioxo-2,3-dihydro-1-benzothiepine-4-carboxamide (Compound 93) (209 mg).

Workup

  1. temperaturethe mixture was refluxed for 18 hours
  2. temperaturecooled to room temperature
  3. extractionthe mixture was extracted with ethyl acetate/THF
  4. washwashed with saturated brine
  5. dry with materialdried with magnesium sulfate
  6. customUnder reduced pressure, the solvent was evaporated
  7. customthe residue was purified with silica gel column chromatography (ethyl acetate/ethanol=3/1)
  8. customrecrystallized from ethanol

Sources & evidence

ORD record
ord-81d90ec8493b4d079fbc23ac656e1229
Source dataset
uspto-grants-2001_05
Patent number
US06235771B1

Reaction notes

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