Dimethylformamide → HCID 21995979, compound

HRID 1978556Notes

Reaction equation

HRID 1978556 reaction equation
[CH2:1]([O:3][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)[CH3:2].C(Cl)(=O)C(Cl)=O.CN(C=O)C.[CH2:37]1[CH2:56][O:55][C:39]2([CH2:44][CH2:43][CH:42]([N:45]([CH2:47][C:48]3[CH:54]=[CH:53][C:51]([NH2:52])=[CH:50][CH:49]=3)[CH3:46])[CH2:41][CH2:40]2)[O:38]1>C1COCC1.O.C(N(CC)CC)C>[CH2:1]([O:3][C:4]1[CH:9]=[CH:8][C:7]([C:10]2[CH:11]=[CH:12][C:13]3[S:19](=[O:20])(=[O:21])[CH2:18][CH2:17][C:16]([C:22]([NH:52][C:51]4[CH:50]=[CH:49][C:48]([CH2:47][N:45]([CH:42]5[CH2:41][CH2:40][C:39]6([O:38][CH2:37][CH2:56][O:55]6)[CH2:44][CH2:43]5)[CH3:46])=[CH:54][CH:53]=4)=[O:23])=[CH:15][C:14]=3[CH:25]=2)=[CH:6][CH:5]=1)[CH3:2]

Participants

8

Reactant 4

HCID 6228DimethylformamideHCID 65578Oxalyl chlorideHCID 10754953HCID 10754953, compoundHCID 219958687-(4-Ethoxyphenyl)-1,1-dioxo-2,3-dihydro-1-benzothiepine-4-carboxylic acid

Product 1

HCID 21995979HCID 21995979, compoundYield 60.4%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent2×HCID 8471TriethylamineSolvent

Procedure

To a solution of 7-(4-ethoxyphenyl)-1,1-dioxo-2,3-dihydro-1-benzothiepine-4-carboxylic acid (180 mg) in THF (10 ml) were added at room temperature oxalyl chloride (0.09 ml) and a drop of DMF, and the mixture was stirred for 1 hour. The mixture was concentrated under reduced pressure, and the residue was dissolved in THF (10 ml). The solution was added dropwise at 0° C. to a solution of 4-[N-(4,4-ethylenedioxycyclohexyl)-N-methylaminomethyl]aniline [0.153 g (0.553 mmol)] and triethylamine (0.14 ml) in THF (5 ml), and the mixture was stirred at room temperature for 16 hours. 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. The solvent was evaporated under reduced pressure to give crude crystals, which were recrystallized from ethanol/diisopropylether to give colorless crystals of 7-(4-ethoxyphenyl)-N-[4-[N-(4,4-ethylenedioxycyclohexyl)-N-methylaminomethyl]phenyl]-1,1-dioxo-2,3-dihydro-1-benzothiepine-4-carboxamide (Compound 18) (187 mg).

Workup

  1. concentrationThe mixture was concentrated under reduced pressure
  2. dissolutionthe residue was dissolved in THF (10 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. customThe solvent was evaporated under reduced pressure
  7. customto give crude crystals, which
  8. customwere recrystallized from ethanol/diisopropylether

Sources & evidence

ORD record
ord-dd7f3b3173e54fe0a01d39f61ae90d38
Source dataset
uspto-grants-2001_05
Patent number
US06235771B1

Reaction notes

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