Potassium Carbonate → HCID 21995947, compound

HRID 1978756Notes

Reaction equation

HRID 1978756 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.[C:33]1(C)[CH:38]=CC=C[CH:34]=1.[CH2:40]([OH:42])[CH3:41].O.B([O-])([O-])O[C:46]1[CH:51]=[CH:50][C:49](OCCOCCC)=[CH:48][C:47]=1[F:59].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>[F:59][C:47]1[CH:48]=[C:49]([CH2:41][CH2:40][O:42][CH2:34][CH2:33][CH3:38])[CH:50]=[CH:51][C:46]=1[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

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 86756841HCID 86756841, compound

Product 1

HCID 21995947HCID 21995947, compound

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 (0.35 g) was added toluene/ethanol/water (10/1/1, 16.3 ml). To the mixture were added 2-fluoro-4-(2-propoxyethoxy)phenyl borate (0.20 g) and potassium carbonate (0.20 g), and the mixture was stirred at room temperature for 30 minutes. To the mixture was added tetrakistriphenylphosphinepalladium (31 mg), and the mixture was refluxed for 14 hours and cooled to room temperature. The reaction solution was poured into water, and the mixture was extracted with ethyl acetate, washed with saturated brine and dried with magnesium sulfate. Under reduced pressure, the solvent was removed, and the residue was purified with silica gel column chromatography (ethyl acetate/ethanol=4/1) and recrystallized from ethanol to give 7-[2-fluoro-4-(2-propoxyethyl)phenyl]-N-[4-[[N-methyl-N-(tetrahydropyran-4-yl)amino]methyl]phenyl]-1,1-dioxo-2,3-dihydro-1-benzothiepine-4-carboxamide (Compound 133) (105 mg).

Workup

  1. temperaturethe mixture was refluxed for 14 hours
  2. temperaturecooled to room temperature
  3. extractionthe mixture was extracted with ethyl acetate
  4. washwashed with saturated brine
  5. dry with materialdried with magnesium sulfate
  6. customUnder reduced pressure, the solvent was removed
  7. customthe residue was purified with silica gel column chromatography (ethyl acetate/ethanol=4/1)
  8. customrecrystallized from ethanol

Sources & evidence

ORD record
ord-5158f60a2f7240f8ab6934cd004a881f
Source dataset
uspto-grants-2001_05
Patent number
US06235771B1

Reaction notes

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