Triethylamine → 7-[4-(2-ethoxyethoxy)phenyl]-N-[4-[[methyl(tetrahydropyran-4-yl)amino]methyl]phenyl]-1,1-dioxo-2,3-dihydro-1$l^{6}-benzothiepine-4-carboxamide

HRID 1978689Notes

Reaction equation

HRID 1978689 reaction equation
[CH2:1]([O:3][CH2:4][CH2:5][O:6][C:7]1[CH:12]=[CH:11][C:10]([C:13]2[CH:14]=[CH:15][C:16]3[S:22](=[O:24])(=[O:23])[CH2:21][CH2:20][C:19]([C:25](O)=[O:26])=[CH:18][C:17]=3[CH:28]=2)=[CH:9][CH:8]=1)[CH3:2].S(Cl)(Cl)=O.[CH3:33][N:34]([CH2:41][C:42]1[CH:48]=[CH:47][C:45]([NH2:46])=[CH:44][CH:43]=1)[CH:35]1[CH2:40][CH2:39][O:38][CH2:37][CH2:36]1.C(N(CC)CC)C>C1COCC1.CN(C=O)C.O>[CH2:1]([O:3][CH2:4][CH2:5][O:6][C:7]1[CH:8]=[CH:9][C:10]([C:13]2[CH:14]=[CH:15][C:16]3[S:22](=[O:23])(=[O:24])[CH2:21][CH2:20][C:19]([C:25]([NH:46][C:45]4[CH:44]=[CH:43][C:42]([CH2:41][N:34]([CH3:33])[CH:35]5[CH2:40][CH2:39][O:38][CH2:37][CH2:36]5)=[CH:48][CH:47]=4)=[O:26])=[CH:18][C:17]=3[CH:28]=2)=[CH:11][CH:12]=1)[CH3:2]

Participants

8

Reactant 4

HCID 8471TriethylamineHCID 24386Thionyl ChlorideHCID 9877845(4-Amino-benzyl)-methyl-(tetrahydro-pyran-4-yl)-amineHCID 219958567-[4-(2-Ethoxyethoxy)phenyl]-1,1-dioxo-2,3-dihydro-1-benzothiepine-4-carboxylic acid

Product 1

HCID 30093957-[4-(2-ethoxyethoxy)phenyl]-N-[4-[[methyl(tetrahydropyran-4-yl)amino]methyl]phenyl]-1,1-dioxo-2,3-dihydro-1$l^{6}-benzothiepine-4-carboxamideYield 44.4%

Reagents, catalysts & solvents 3

HCID 6228DimethylformamideCatalystHCID 962WaterSolventHCID 8028TetrahydrofuranSolvent2×

Procedure

In THF (72 ml) was dissolved 7-[4-(2-ethoxyethoxy)phenyl]-1,1-dioxo-2,3-dihydro-1-benzothiepine-4-carboxylic acid (3.6 g). To the mixture were added under ice-cooling thionyl chloride (0.93 ml) and DMF (three drops), and the mixture was stirred at room temperature for 30 minutes. The reaction mixture was added dropwise to a solution of 4-[[N-methyl-N-(tetrahydropyran-4-yl)amino]methyl]aniline (2.23 g) and triethylamine (5.0 ml) in THF (67 ml), and the mixture was stirred at room temperature for 1 hour. The reaction mixture was added to water, and the mixture was extracted with ethyl acetate, 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 (ethyl acetate/ethanol=3/1) and recrystallized from ethanol to give 7-[4-(2-ethoxyethoxy)phenyl]-N-[4-[[N-methyl-N-(tetrahydropyran-4-yl)amino]methyl]phenyl]-1,1-dioxo-2,3-dihydro-1-benzothiepine-4-carboxamide (Compound 84) (2.4 g).

Workup

  1. additionTo the mixture were added under ice-
  2. stirringthe mixture was stirred at room temperature for 1 hour
  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 evaporated
  7. customthe residue was purified with silica gel column chromatography (ethyl acetate/ethanol=3/1)
  8. customrecrystallized from ethanol

Sources & evidence

ORD record
ord-77739fe31e9a4f7aa69a1d6f9beacfc9
Source dataset
uspto-grants-2001_05
Patent number
US06235771B1

Reaction notes

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