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

HRID 1978611Notes

Reaction equation

HRID 1978611 reaction equation
[Br:1][C:2]1[CH:3]=[CH:4][C:5]2[S:11](=[O:13])(=[O:12])[CH2:10][CH2:9][C:8]([C:14]([OH:16])=O)=[CH:7][C:6]=2[CH:17]=1.S(Cl)(Cl)=O.CN(C=O)C.[CH3:27][N:28]([CH2:35][C:36]1[CH:42]=[CH:41][C:39]([NH2:40])=[CH:38][CH:37]=1)[CH:29]1[CH2:34][CH2:33][O:32][CH2:31][CH2:30]1>C1COCC1.C(N(CC)CC)C>[Br:1][C:2]1[CH:3]=[CH:4][C:5]2[S:11](=[O:12])(=[O:13])[CH2:10][CH2:9][C:8]([C:14]([NH:40][C:39]3[CH:41]=[CH:42][C:36]([CH2:35][N:28]([CH3:27])[CH:29]4[CH2:34][CH2:33][O:32][CH2:31][CH2:30]4)=[CH:37][CH:38]=3)=[O:16])=[CH:7][C:6]=2[CH:17]=1

Participants

7

Reactant 4

HCID 6228DimethylformamideHCID 24386Thionyl ChlorideHCID 9877845(4-Amino-benzyl)-methyl-(tetrahydro-pyran-4-yl)-amineHCID 219959787-Bromo-1,1-dioxo-2,3-dihydro-1-benzothiepine-4-carboxylic acid

Product 1

HCID 219957067-bromo-N-[4-[[N-methyl-N-(tetrahydropyran-4-yl)amino]methyl]phenyl]-1,1-dioxo-2,3-dihydro-1-benzothiepine-4-carboxamideYield 67.5%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolvent2×HCID 8471TriethylamineSolvent

Procedure

To a suspension of 7-bromo-1,1-dioxo-2,3-dihydro-1-benzothiepine-4-carboxylic acid (4.47 g) in THF (90 ml) were added at room temperature thionyl chloride (1.03 ml) and DMF (1 ml), and the mixture was stirred for 1 hour and added dropwise to a solution of 4-[[N-methyl-N-(tetrahydropyran-4-yl)amino]methyl]aniline (3.41 g) and triethylamine (7.9 ml) in THF (30 ml), at 0° C. The mixture was stirred for 3 hours and concentrated under reduced pressure, to which were added water. Precipitated colorless crystals were collected by filtration, and the crystals were washed with water, ethanol, 2-propanol and diisopropylether to give colorless crystals of 7-bromo-N-[4-[[N-methyl-N-(tetrahydropyran-4-yl)amino]methyl]phenyl]-1,1-dioxo-2,3-dihydro-1-benzothiepine-4-carboxamide (4.94 g).

Workup

  1. stirringThe mixture was stirred for 3 hours
  2. concentrationconcentrated under reduced pressure, to which
  3. additionwere added water
  4. customPrecipitated colorless crystals
  5. filtrationwere collected by filtration
  6. washthe crystals were washed with water, ethanol, 2-propanol and diisopropylether

Sources & evidence

ORD record
ord-c8f1ffe61af544ce872b7f7cdd5ea2a2
Source dataset
uspto-grants-2001_05
Patent number
US06235771B1

Reaction notes

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