1-(Toluene-4-sulfonyl)-1,2,3,4-tetrahydrobenzo[b]azepin-5-one

Uses

1,2,3,4-Tetrahydro-1-[(4-methylphenyl)sulfonyl]-5H-1-benzazepin-5-one is an intermediate used to prepare nonpeptide vasopressin V2 receptor antagonist tetrahydro-1H-benzazepines. It is also used to synthesize 4''-[(4,4-difluoro-5-methylidene-2,3,4,5-tetrahydro-1H-1-benzoazepin-1-yl)carbonyl]-2-phenylbenzanilide derivatives as non-peptide arginine vasopressin antagonists for both V1A and V2 receptors.

Synthesis

To a stirred solution of 1,2,3,4-tetrahydrobenzo[b]azepin-5-one (50 g, 0.31 mol) in dichloromethane (DCM, 250 mL) was added pyridine (175 mL). The reaction mixture was cooled in an ice bath, followed by the slow addition of p-toluenesulfonyl chloride (TsCl, 84 g, 0.44 mol). When the addition was complete, the mixture was gradually warmed to room temperature and stirred continuously overnight. Upon completion of the reaction, the mixture was diluted with water (750 mL) and subsequently extracted with dichloromethane (300 mL x 3). The organic phases were combined, washed sequentially with water and saturated saline, dried over anhydrous sodium sulfate (Na2SO4) and concentrated under reduced pressure to remove the solvent. The resulting residue was washed with mixed solvents (petroleum ether/ethyl acetate = 70:1) to afford the target product 1-(toluene-4-sulfonyl)-1,2,3,4-tetrahydrobenzo[b]azepin-5-one as a light yellow solid (97 g, 99% yield). eSI MS m/z = 316.05 [M + H]+.

References

[1] Patent: WO2017/123884, 2017, A1. Location in patent: Page/Page column 92
[2] Heterocycles, 2000, vol. 52, # 1, p. 81 - 84
[3] Patent: WO2005/37796, 2005, A1. Location in patent: Page/Page column 160
[4] Patent: US2015/291533, 2015, A1. Location in patent: Paragraph 0137-0139