Potassium Carbonate → HCID 21995922, compound

HRID 1978684Notes

Reaction equation

HRID 1978684 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.B([O-])([O-])O[C:35]1[CH:40]=[CH:39][C:38]([O:41][CH2:42][CH2:43][CH3:44])=[C:37]([C:45]#[N:46])[CH:36]=1.C(=O)([O-])[O-].[K+].[K+].CC1C=CC=CC=1P(C1C=CC=CC=1C)C1C=CC=CC=1C>C([O-])(=O)C.[Pd+2].C([O-])(=O)C.O.C1(C)C=CC=CC=1.C(O)C.O>[C:45]([C:37]1[CH:36]=[CH:35][C:40]([C:2]2[CH:3]=[CH:4][C:5]3[S:11](=[O:13])(=[O:12])[CH2:10][CH2:9][C:8]([C:14]([NH:16][C:17]4[CH:18]=[CH:19][C:20]([CH2:23][N:24]([CH3:31])[CH:25]5[CH2:30][CH2:29][O:28][CH2:27][CH2:26]5)=[CH:21][CH:22]=4)=[O:15])=[CH:7][C:6]=3[CH:32]=2)=[CH:39][C:38]=1[O:41][CH2:42][CH2:43][CH3:44])#[N:46]

Participants

8

Reactant 4

HCID 11430Potassium CarbonateHCID 80271Tri-o-tolylphosphineHCID 219957067-bromo-N-[4-[[N-methyl-N-(tetrahydropyran-4-yl)amino]methyl]phenyl]-1,1-dioxo-2,3-dihydro-1-benzothiepine-4-carboxamideHCID 86756813HCID 86756813, compound

Product 1

HCID 21995922HCID 21995922, compoundYield 52.6%

Reagents, catalysts & solvents 3

HCID 167845palladium(II) acetateCatalystHCID 962WaterSolventHCID 86587398Ethanol toluene waterSolvent

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, 13.2 ml) and then were added 3-cyano-4-propoxyphenyl borate (205 mg) and potassium carbonate (234 mg), and the mixture was stirred at room temperature for 30 minutes. To the mixture were added palladium acetate (8.6 mg) and tris(2-methylphenyl)phosphine (22.4 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-propoxyphenyl)-N-[4-[[N-methyl-N-(tetrahydropyran-4-yl)amino]methyl]phenyl]-1,1-dioxo-2,3-dihydro-1-benzothiepine-4-carboxamide (Compound 94) (243 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-e203c4f4e5fd493b86103a429a2fd61f
Source dataset
uspto-grants-2001_05
Patent number
US06235771B1

Reaction notes

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