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

HRID 1978778Notes

Reaction equation

HRID 1978778 reaction equation
C(O)C.B([O-])([O-])O[C:6]1[CH:11]=[CH:10][C:9]([O:12][CH2:13][CH2:14][CH3:15])=[C:8]([CH3:16])[CH:7]=1.Br[C:20]1[CH:21]=[CH:22][C:23]2[S:29](=[O:31])(=[O:30])[CH2:28][CH2:27][C:26]([C:32]([NH:34][C:35]3[CH:40]=[CH:39][C:38]([CH2:41][N:42]([CH3:49])[CH:43]4[CH2:48][CH2:47][O:46][CH2:45][CH2:44]4)=[CH:37][CH:36]=3)=[O:33])=[CH:25][C:24]=2[CH:50]=1.C(=O)([O-])[O-].[K+].[K+]>C1(C)C=CC=CC=1.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>[CH3:16][C:8]1[CH:7]=[C:6]([C:20]2[CH:21]=[CH:22][C:23]3[S:29](=[O:31])(=[O:30])[CH2:28][CH2:27][C:26]([C:32]([NH:34][C:35]4[CH:40]=[CH:39][C:38]([CH2:41][N:42]([CH3:49])[CH:43]5[CH2:48][CH2:47][O:46][CH2:45][CH2:44]5)=[CH:37][CH:36]=4)=[O:33])=[CH:25][C:24]=3[CH:50]=2)[CH:11]=[CH:10][C:9]=1[O:12][CH2:13][CH2:14][CH3:15]

Participants

8

Reactant 4

HCID 702EthanolHCID 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 867568453-Methyl-4-propoxyphenyl borate

Product 1

HCID 98299237-(3-methyl-4-propoxyphenyl)-N-[4-[[N-methyl-N-(tetrahydropyran-4-yl)amino]methyl]phenyl]-1,1-dioxo-2,3-dihydro-1-benzothiepine-4-carboxamideYield 47.4%

Reagents, catalysts & solvents 3

HCID 178418397HCID 178418397, compoundCatalystHCID 962WaterSolvent2×HCID 1140TolueneSolvent

Procedure

In toluene (23 ml), ethanol (2.3 ml) and water (2.3 ml) were suspended 3-methyl-4-propoxyphenyl borate (219 mg), 7-bromo-N-[4-[[N-methyl-N-(tetrahydropyran-4-yl)amino]methyl]phenyl]-1,1-dioxo-2,3-dihydro-1-benzothiepine-4-carboxamide (450 mg) and potassium carbonate (312 mg), and the suspension was stirred under argon atmosphere for 30 minutes. To the mixture was added tetrakistriphenylphosphinepalladium (70 mg), and the mixture was stirred, under argon atmosphere, at 100° C. for 8 hours and cooled. To the mixture was added water, and the mixture was extracted with ethyl acetate (twice). The organic layer was 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 and recrystallized from ethanol (125 ml) to give colorless crystals of 7-(3-methyl-4-propoxyphenyl)-N-[4-[[N-methyl-N-(tetrahydropyran-4-yl)amino]methyl]phenyl]-1,1-dioxo-2,3-dihydro-1-benzothiepine-4-carboxamide (Compound 137) (242 mg).

Workup

  1. stirringthe mixture was stirred, under argon atmosphere, at 100° C. for 8 hours
  2. temperaturecooled
  3. extractionthe mixture was extracted with ethyl acetate (twice)
  4. washThe organic layer was washed 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
  8. customrecrystallized from ethanol (125 ml)

Sources & evidence

ORD record
ord-e56d32ec44cf4728a9cb29025560aecb
Source dataset
uspto-grants-2001_05
Patent number
US06235771B1

Reaction notes

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