Cysteamine Hydrochloride → (1)Benzothieno(2,3-f)-1,4-thiazepin-5(2H)-one, 3,4-dihydro-9-methoxy-

HRID 976241Notes

Reaction equation

HRID 976241 reaction equation
ClCOC1C2C=CC=CC=2SC=1C(OC)=O.Cl[C:18]1[C:19]2[CH:29]=[C:28]([O:30][CH3:31])[CH:27]=[CH:26][C:20]=2[S:21][C:22]=1[C:23](Cl)=[O:24].Cl.[NH2:33][CH2:34][CH2:35][SH:36].C1CCN2C(=NCCC2)CC1>CN(C=O)C.C(OCC)(=O)C.CO>[CH3:31][O:30][C:28]1[CH:27]=[CH:26][C:20]2[S:21][C:22]3[C:23](=[O:24])[NH:33][CH2:34][CH2:35][S:36][C:18]=3[C:19]=2[CH:29]=1

Participants

8

Reactant 4

HCID 9082Cysteamine HydrochlorideHCID 811841,8-Diazabicyclo(5.4.0)undec-7-eneHCID 101991093-Chloro-5-methoxybenzo[b]thiophene-2-carbonyl chlorideHCID 19966841Methyl 3-chloromethoxy-benzo[b]thiophene-2-carboxylate

Product 1

HCID 461195(1)Benzothieno(2,3-f)-1,4-thiazepin-5(2H)-one, 3,4-dihydro-9-methoxy-Yield 74%

Reagents, catalysts & solvents 3

HCID 887MethanolSolventHCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a room temperature solution of methyl 3-chloromethoxy-benzo[b]thiophene-2-carboxylate (500 mg, 1.95 mmol) [prepared by reaction of the known 3-chloro-5-methoxy-benzo[b]thiophene-2-carbonyl chloride with methanol- [J. Med. Chem., 35:958 (1992)]] in 20 mL of DMF is added cysteamine-HCl (885 mg, 7.79 mmol) followed by DBU (2.33 mL, 15.58 mmol). The reaction mixture is stirred at room temperature for 1.5 hours then warmed to 70° C. The mixture is diluted with ethyl acetate and washed with aqueous HCl, water and brine. The organic layer is dried over MgSO4, filtered and concentrated in vacuo. The crude product is recrystallized from hexane and ethyl acetate to provide 2,3-dihydro-9-methoxy[1]benzothieno[2,3-f]-1,4-thiazepin-5(4H)-one in 74% yield, mp 209°-209.5° C.

Workup

  1. temperaturethen warmed to 70° C
  2. washwashed with aqueous HCl, water and brine
  3. dry with materialThe organic layer is dried over MgSO4
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo
  6. customThe crude product is recrystallized from hexane and ethyl acetate

Sources & evidence

ORD record
ord-8bbe948c3ffb47baa342c1b7ef02756d
Source dataset
uspto-grants-1997_03
Patent number
US05612330

Reaction notes

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