Potassium Carbonate → N-[4-[[N-methyl-N-(tetrahydropyran-4-yl)amino]methyl]phenyl]-7-[4-(3-propoxypropoxy)phenyl]-1,1-dioxo-2,3-dihydro-1-benzothiepine-4-carboxamide

HRID 1978702Notes

Reaction equation

HRID 1978702 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][CH2:54][CH2:55][O:56][CH2:57][CH2:58][CH3:59])=[CH:48][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>[CH3:31][N:24]([CH2:23][C:20]1[CH:21]=[CH:22][C:17]([NH:16][C:14]([C:8]2[CH2:9][CH2:10][S:11](=[O:13])(=[O:12])[C:5]3[CH:4]=[CH:3][C:2]([C:46]4[CH:51]=[CH:50][C:49]([O:52][CH2:53][CH2:54][CH2:55][O:56][CH2:57][CH2:58][CH3:59])=[CH:48][CH:47]=4)=[CH:32][C:6]=3[CH:7]=2)=[O:15])=[CH:18][CH:19]=1)[CH:25]1[CH2:30][CH2:29][O:28][CH2:27][CH2:26]1

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 867568184-(3-Propoxypropoxy)phenyl borate

Product 1

HCID 21995790N-[4-[[N-methyl-N-(tetrahydropyran-4-yl)amino]methyl]phenyl]-7-[4-(3-propoxypropoxy)phenyl]-1,1-dioxo-2,3-dihydro-1-benzothiepine-4-carboxamideYield 67%

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 (300 mg) were added toluene/ethanol/water (10/1/1, 19.2 ml) and then were added 4-(3-propoxypropoxy)phenyl borate (165 mg) and potassium carbonate (175 mg), and the mixture was stirred at room temperature for 30 minutes. To the mixture was added tetrakistriphenylphosphinepalladium (27 mg), and the mixture was refluxed for 14 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 N-[4-[[N-methyl-N-(tetrahydropyran-4-yl)amino]methyl]phenyl]-7-[4-(3-propoxypropoxy)phenyl]-1,1-dioxo-2,3-dihydro-1-benzothiepine-4-carboxamide (Compound 103) (245 mg).

Workup

  1. temperaturethe mixture was refluxed for 14 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-26018b43637e4de5843734366e632b14
Source dataset
uspto-grants-2001_05
Patent number
US06235771B1

Reaction notes

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