Ethanol → HCID 21995686, compound

HRID 1978750Notes

Reaction equation

HRID 1978750 reaction equation
C(O)C.B([O-])([O-])O[C:6]1[CH:11]=[CH:10][C:9]([O:12][CH2:13][CH2:14][O:15][CH2:16][CH3:17])=[C:8]([CH3:18])[CH:7]=1.Br[C:22]1[CH:23]=[CH:24][C:25]2[S:31](=[O:33])(=[O:32])[CH2:30][CH2:29][C:28]([C:34]([NH:36][C:37]3[CH:42]=[CH:41][C:40]([CH2:43][N:44]([CH3:51])[CH:45]4[CH2:50][CH2:49][O:48][CH2:47][CH2:46]4)=[CH:39][CH:38]=3)=[O:35])=[CH:27][C:26]=2[CH:52]=1.C(=O)([O-])[O-].[K+].[K+]>C1(C)C=CC=CC=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.O>[CH2:16]([O:15][CH2:14][CH2:13][O:12][C:9]1[CH:10]=[CH:11][C:6]([C:22]2[CH:23]=[CH:24][C:25]3[S:31](=[O:33])(=[O:32])[CH2:30][CH2:29][C:28]([C:34]([NH:36][C:37]4[CH:42]=[CH:41][C:40]([CH2:43][N:44]([CH3:51])[CH:45]5[CH2:50][CH2:49][O:48][CH2:47][CH2:46]5)=[CH:39][CH:38]=4)=[O:35])=[CH:27][C:26]=3[CH:52]=2)=[CH:7][C:8]=1[CH3:18])[CH3:17]

Participants

9

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 86756838HCID 86756838, compound

Product 1

HCID 21995686HCID 21995686, compoundYield 51.9%

Reagents, catalysts & solvents 4

HCID 178418397HCID 178418397, compoundCatalystHCID 962WaterSolventHCID 1140TolueneSolventHCID 57417360Sodium chloride; waterSolvent

Procedure

In toluene (10 ml), ethanol (1 ml) and water (1 ml) were suspended 4-(2-ethoxyethoxy)-3-methylphenyl borate (119 mg), 7-bromo-N-[4-[[N-methyl-N-(tetrahydropyran-4-yl)amino]methyl]phenyl]-1,1-dioxo-2,3-dihydro-1-benzothiepine-4-carboxamide (212 mg) and potassium carbonate (147 mg), and the suspension was stirred under argon atmosphere for 30 minutes. To the mixture was added tetrakistriphenylphosphinepalladium (33 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=7:1) and recrystallized from ethanol (22.5 ml) to give colorless crystals of 7-[4-(2-ethoxyethoxy)-3-methyl-phenyl]-N-[4-[[N-methyl-N-(tetrahydropyran-4-yl)amino]methyl]phenyl]-1,1-dioxo-2,3-dihydro-1-benzothiepine-4-carboxamide (Compound 129) (131 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. dry with materialThe organic layer was dried with magnesium sulfate
  5. customUnder reduced pressure, the solvent was evaporated
  6. customthe residue was purified with silica gel column chromatography (ethyl acetate:methanol=7:1)
  7. customrecrystallized from ethanol (22.5 ml)

Sources & evidence

ORD record
ord-1ab3360083984ab0918db0d195cff48a
Source dataset
uspto-grants-2001_05
Patent number
US06235771B1

Reaction notes

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