Ethanol → HCID 21995927, compound

HRID 1978752Notes

Reaction equation

HRID 1978752 reaction equation
C(O)C.B([O-])([O-])O[C:6]1[CH:11]=[CH:10][C:9]([O:12][CH2:13][CH2:14][CH2:15][O:16][CH2:17][CH3:18])=[C:8]([Cl:19])[CH:7]=1.Br[C:23]1[CH:24]=[CH:25][C:26]2[S:32](=[O:34])(=[O:33])[CH2:31][CH2:30][C:29]([C:35]([NH:37][C:38]3[CH:43]=[CH:42][C:41]([CH2:44][N:45]([CH3:52])[CH:46]4[CH2:51][CH2:50][O:49][CH2:48][CH2:47]4)=[CH:40][CH:39]=3)=[O:36])=[CH:28][C:27]=2[CH:53]=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>[Cl:19][C:8]1[CH:7]=[C:6]([C:23]2[CH:24]=[CH:25][C:26]3[S:32](=[O:34])(=[O:33])[CH2:31][CH2:30][C:29]([C:35]([NH:37][C:38]4[CH:43]=[CH:42][C:41]([CH2:44][N:45]([CH3:52])[CH:46]5[CH2:51][CH2:50][O:49][CH2:48][CH2:47]5)=[CH:40][CH:39]=4)=[O:36])=[CH:28][C:27]=3[CH:53]=2)[CH:11]=[CH:10][C:9]=1[O:12][CH2:13][CH2:14][CH2:15][O:16][CH2:17][CH3:18]

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 86756839HCID 86756839, compound

Product 1

HCID 21995927HCID 21995927, compoundYield 60.7%

Reagents, catalysts & solvents 4

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

Conditions

Temperature
100 °C

Procedure

In toluene (15 ml), ethanol (1.5 ml) and water (1.5 ml) were suspended 3-chloro-4-(3-ethoxypropoxy)phenyl borate (194 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). Under argon atmosphere, the suspension was stirred for 30 minutes, and to the mixture was added tetrakistriphenylphosphinepalladium (47 mg). Under argon atmosphere, the mixture was heated at 100° C. for 8 hours and cooled. To the mixture was added saturated brine, and the mixture was extracted with ethyl acetate. 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:ethano=18:1) and recrystallized from ethanol (23 ml) to give colorless crystals of 7-[3-chloro-4-(3-ethoxypropoxy)phenyl]-N-[4-[[N-methyl-N-(tetrahydropyran-4-yl)amino]methyl]phenyl]-1,1-dioxo-2,3-dihydro-1-benzothiepine-4-carboxamide (Compound 131) (229 mg).

Workup

  1. temperaturecooled
  2. extractionthe mixture was extracted with ethyl acetate
  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:ethano=18:1)
  6. customrecrystallized from ethanol (23 ml)

Sources & evidence

ORD record
ord-21a1ded241f549b6a31226a5df5f6562
Source dataset
uspto-grants-2001_05
Patent number
US06235771B1

Reaction notes

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