Ethanol → HCID 21995741, compound

HRID 1978751Notes

Reaction equation

HRID 1978751 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](=[O:36])([O-])[O-].[K+].[K+].[CH2:39]([OH:41])[CH3:40].O.[C:43]1(C)[CH:48]=[CH:47][CH:46]=[CH:45][CH:44]=1>[Cl-].[Na+].O.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>[CH2:39]([O:41][CH2:5][C:6]([CH3:32])([CH3:7])[CH2:33][O:36][C:43]1[CH:44]=[CH:45][C:46]([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: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:47][CH:48]=1)[CH3:40]

Participants

8

Reactant 5

HCID 702EthanolHCID 962WaterHCID 1140TolueneHCID 11430Potassium CarbonateHCID 219957067-bromo-N-[4-[[N-methyl-N-(tetrahydropyran-4-yl)amino]methyl]phenyl]-1,1-dioxo-2,3-dihydro-1-benzothiepine-4-carboxamide

Product 1

HCID 21995741HCID 21995741, compound

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 57417360Sodium chloride; waterSolvent

Conditions

Temperature
100 °C

Procedure

A mixture of 4-(3-ethoxy-2,2-dimethyl)propoxyphenyl borate (189 mg), 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) and potassium carbonate (208 mg) was suspended in toluene (15 ml), ethanol (1.5 ml) and water (1.5 ml), and the suspension was stirred under argon atmosphere for 30 minutes. To the mixture was added tetrakistriphenylphosphinepalladium (47 mg), and the mixture was stirred under argon atmosphere at 100° C. for 8 hours and cooled. To the mixture was added saturated brine, and the mixture was extracted with ethyl acetate (twice). The organic layer was dried with magnesium sulfate. Under reduced pressure, the solvent was evaporated, and the residue was purified with silica gel column chromatography (ethyl acetate:methanol=8:1) and recrystallized from ethanol (22.5 ml) to give colorless crystals of 7-[4-(3-ethoxy-2,2-dimethylpropoxy)phenyl]-N-[4-[[N-methyl-N-(tetrahydropyran-4-yl)amino]methyl]phenyl]-1,1-dioxo-2,3-dihydro-1-benzothiepine-4-carboxamide (Compound 130) (175 mg).

Workup

  1. temperaturecooled
  2. extractionthe mixture was extracted with ethyl acetate (twice)
  3. dry with materialThe organic layer was dried with magnesium sulfate
  4. customUnder reduced pressure, the solvent was evaporated
  5. customthe residue was purified with silica gel column chromatography (ethyl acetate:methanol=8:1)
  6. customrecrystallized from ethanol (22.5 ml)

Sources & evidence

ORD record
ord-e8aec303f7db4883bb2cb59a1243ff33
Source dataset
uspto-grants-2001_05
Patent number
US06235771B1

Reaction notes

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