Ethanol → HCID 21995687, compound

HRID 1978781Notes

Reaction equation

HRID 1978781 reaction equation
C(O)C.B([O-])([O-])O[C:6]1[O:7][C:8]2[CH:14]=[CH:13][C:12]([O:15][CH2:16][CH2:17][O:18][CH2:19][CH2:20][CH3:21])=[CH:11][C:9]=2[CH:10]=1.Br[C:25]1[CH:26]=[CH:27][C:28]2[S:34](=[O:36])(=[O:35])[CH2:33][CH2:32][C:31]([C:37]([NH:39][C:40]3[CH:45]=[CH:44][C:43]([CH2:46][N:47]([CH3:54])[CH:48]4[CH2:53][CH2:52][O:51][CH2:50][CH2:49]4)=[CH:42][CH:41]=3)=[O:38])=[CH:30][C:29]=2[CH:55]=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>[CH3:54][N:47]([CH2:46][C:43]1[CH:44]=[CH:45][C:40]([NH:39][C:37]([C:31]2[CH2:32][CH2:33][S:34](=[O:36])(=[O:35])[C:28]3[CH:27]=[CH:26][C:25]([C:6]4[O:7][C:8]5[CH:14]=[CH:13][C:12]([O:15][CH2:16][CH2:17][O:18][CH2:19][CH2:20][CH3:21])=[CH:11][C:9]=5[CH:10]=4)=[CH:55][C:29]=3[CH:30]=2)=[O:38])=[CH:41][CH:42]=1)[CH:48]1[CH2:53][CH2:52][O:51][CH2:50][CH2:49]1

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 131722582HCID 131722582, compound

Product 1

HCID 21995687HCID 21995687, compoundYield 52.6%

Reagents, catalysts & solvents 3

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

Procedure

In toluene (15 ml), ethanol (1.5 ml) and water (1.5 ml) were suspended 5-propoxyethoxy-benzofuran-2-yl borate (198 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), 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 water, and the mixture was extracted with ethyl acetate. 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 to give colorless crystals of N-[4-[[N-methyl-N-(tetrahydropyran-4-yl)amino]methyl]phenyl]-1,1-dioxo-7-(5-propoxyethoxybenzofuran-2-yl)-2,3-dihydro-1-benzothiepine-4-carboxamide (Compound 140) (200 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
  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

Sources & evidence

ORD record
ord-1dfa21a0aec742758ca52e8895e552be
Source dataset
uspto-grants-2001_05
Patent number
US06235771B1

Reaction notes

Loading…