Dimethylformamide → N-[4-[N-methyl-N-(tetrahydropyran-4-yl)aminomethyl]phenyl]-7-(4-propylphenyl)-1,1-dioxo-2,3-dihydro-1-benzothiepine-4-carboxamide

HRID 1978561Notes

Reaction equation

HRID 1978561 reaction equation
[CH2:1]([C:4]1[CH:9]=[CH:8][C:7]([C:10]2[CH:11]=[CH:12][C:13]3[S:19](=[O:21])(=[O:20])[CH2:18][CH2:17][C:16]([C:22](O)=[O:23])=[CH:15][C:14]=3[CH:25]=2)=[CH:6][CH:5]=1)[CH2:2][CH3:3].S(Cl)(Cl)=O.CN(C=O)C.[CH3:35][N:36]([CH2:43][C:44]1[CH:50]=[CH:49][C:47]([NH2:48])=[CH:46][CH:45]=1)[CH:37]1[CH2:42][CH2:41][O:40][CH2:39][CH2:38]1>C1COCC1.O.C(N(CC)CC)C>[CH3:35][N:36]([CH2:43][C:44]1[CH:45]=[CH:46][C:47]([NH:48][C:22]([C:16]2[CH2:17][CH2:18][S:19](=[O:21])(=[O:20])[C:13]3[CH:12]=[CH:11][C:10]([C:7]4[CH:8]=[CH:9][C:4]([CH2:1][CH2:2][CH3:3])=[CH:5][CH:6]=4)=[CH:25][C:14]=3[CH:15]=2)=[O:23])=[CH:49][CH:50]=1)[CH:37]1[CH2:42][CH2:41][O:40][CH2:39][CH2:38]1

Participants

8

Reactant 4

HCID 6228DimethylformamideHCID 24386Thionyl ChlorideHCID 9877845(4-Amino-benzyl)-methyl-(tetrahydro-pyran-4-yl)-amineHCID 219958817-(4-Propylphenyl)-1,1-dioxo-2,3-dihydro-1-benzothiepine-4-carboxylic acid

Product 1

HCID 3009390N-[4-[N-methyl-N-(tetrahydropyran-4-yl)aminomethyl]phenyl]-7-(4-propylphenyl)-1,1-dioxo-2,3-dihydro-1-benzothiepine-4-carboxamideYield 63.5%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent2×HCID 8471TriethylamineSolvent

Procedure

To a solution of 7-(4-propylphenyl)-1,1-dioxo-2,3-dihydro-1-benzothiepine-4-carboxylic acid (200 mg) in THF (5 ml) were added at room temperature thionyl chloride (0.09 ml) and a drop of DMF, and the mixture was stirred for 1 hour. The solvent was evaporated under reduced pressure, and the residue was dissolved in THF (12 ml). The solution was added dropwise at 0° C. to a solution of 4-[N-methyl-N-(tetrahydropyran-4-yl)aminomethyl]aniline[122 mg (0.55 mmol)] and triethylamine (0.14 ml) in THF (2 ml), and the mixture was stirred at room temperature for 4 hours. To the mixture was added water, and the mixture was extracted with ethyl acetate. The organic layer was washed with saturated brine, dried with magnesium sulfate and concentrated under reduced pressure to give pale yellow crystals, which were recrystallized from ethanol to give colorless crystals of N-[4-[N-methyl-N-(tetrahydropyran-4-yl)aminomethyl]phenyl]-7-(4-propylphenyl)-1,1-dioxo-2,3-dihydro-1-benzothiepine-4-carboxamide (Compound 27) (195.0 mg).

Workup

  1. customThe solvent was evaporated under reduced pressure
  2. dissolutionthe residue was dissolved in THF (12 ml)
  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. concentrationconcentrated under reduced pressure
  7. customto give pale yellow crystals, which
  8. customwere recrystallized from ethanol

Sources & evidence

ORD record
ord-ca4ae79166a646d58b22dc2680c0a256
Source dataset
uspto-grants-2001_05
Patent number
US06235771B1

Reaction notes

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