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

HRID 2395538Notes

Reaction equation

HRID 2395538 reaction equation
Cl[C:2]1[C:3]2[CH:14]=[C:13]([O:15][CH3:16])[CH:12]=[CH:11][C:4]=2[S:5][C:6]=1[C:7]([O:9]C)=O.ClC1C2C=C(OC)C=CC=2SC=1C(Cl)=O.Cl.[NH2:33][CH2:34][CH2:35][SH:36].C1CCN2C(=NCCC2)CC1>CN(C=O)C.C(OCC)(=O)C.CO>[CH3:16][O:15][C:13]1[CH:12]=[CH:11][C:4]2[S:5][C:6]3[C:7](=[O:9])[NH:33][CH2:34][CH2:35][S:36][C:2]=3[C:3]=2[CH:14]=1

Participants

8

Reactant 4

HCID 9082Cysteamine HydrochlorideHCID 811841,8-Diazabicyclo(5.4.0)undec-7-eneHCID 2801561Methyl 3-chloro-5-methoxy-1-benzothiophene-2-carboxylateHCID 101991093-Chloro-5-methoxybenzo[b]thiophene-2-carbonyl chloride

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-chloro-5-methoxy-benzo[b]thiophene-2-carboxylate (500 mg, 1.95 mmols) [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-3ebf3152ba274f6684e1b89a94db8001
Source dataset
uspto-grants-1996_02
Patent number
US05489586

Reaction notes

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