3-Bromo-1,3,4,5-tetrahydro-2H-benzo[b]azepin-2-one Chemical Properties

Melting point:

164 °C

Boiling point:

383.2±42.0 °C(Predicted)

Density 

1.492±0.06 g/cm3(Predicted)

Flash point:

185.542℃

storage temp. 

Keep in dark place,Sealed in dry,Room Temperature

solubility 

slightly soluble in ethanol, benzene, acetone, insoluble in water

pka

13.59±0.40(Predicted)

Appearance

Off-white to light yellow Solid

InChI

InChI=1S/C10H10BrNO/c11-8-6-5-7-3-1-2-4-9(7)12-10(8)13/h1-4,8H,5-6H2,(H,12,13)

InChIKey

JMXPGCGROVEPID-UHFFFAOYSA-N

SMILES

N1C2=CC=CC=C2CCC(Br)C1=O

CAS DataBase Reference

86499-96-9(CAS DataBase Reference)

3-Bromo-1,3,4,5-tetrahydro-2H-benzo[b]azepin-2-one Usage And Synthesis

Uses

3-Bromo-1,3,4,5-tetrahydro-2H-benzo[b]azepin-2-one is an intermediate in the synthesis of Benazepril Hydrochloride. Benazepril Hydrochloride is a first-line antihypertensive drug recommended by the WHO. It is a chiral drug with excellent clinical efficacy, strong safety and tiny side effects in the international antihypertensive drugs of angiotensin converting enzyme inhibitors.

Chemical Properties

White or almost white crystalline

Preparation

The preparation of 3-Bromo-1,3,4,5-tetrahydro-2H-benzo[b]azepin-2-one is as follows:10 parts by weight of the heated melted polyphosphoric acid was added to the drying kettle, With stirring, The above 2-bromo-3,4-dihydro-N-hydroxy- (2H) -naphthalimide was added in portions at a temperature of 60 ° C, Insulation reaction for 20 hours; The reaction solution was added dropwise to 12.5 parts by weight of water to carry out hydrolysis, Still Washed to give 3-bromo-1,3,4,5-tetrahydro-2H-1-benzazepin-2-one crude; 10 parts by weight of methanol and 0.1 part by weight of activated carbon were added, Heating decolorization, After filtration, the filtrate was cooled to 10 ° C for 20 hours, centrifuged, washed and dried to give 3-bromo-1,3,4,5-tetrahydro-2H-1-benzazepan-2-one. The purity of the product was 3, 10-bromo-1,3,4,5-tetrahydro-2H-1-benzazepan-2-one as high as 99.6% and the yield was as high as 98%.

Synthesis

General procedure for the synthesis of 3-bromo-1,3,4,5-tetrahydro-2H-1-benzazepin-2-one from 1,3,4,5-tetrahydro-2H-1-benzazepin-2-one: 1,3,4,5-tetrahydro-2H-1-benzazepin-2-one (1.0 g, 6.20 mmol) was dissolved in anhydrous CHCl3 (15 ml) and cooled to 0 °C ( ice-salt bath). Under argon protection, PCl5 (1.5 g, 7.20 mmol) and I2 (15 mg) were added and stirred at 0 °C for 30 min. Subsequently, Br2 (0.39 ml, 7.51 mmol) was added dropwise to the reaction solution, which was slowly warmed to room temperature and refluxed for 4.0 h under argon protection. After completion of the reaction, the mixture was poured into ice water (20 g) and the organic and aqueous phases were separated after thorough stirring. The aqueous phase was extracted with CHCl3 (25 ml), the organic phases were combined, washed with H2O (5.0 ml), dried over anhydrous MgSO4, filtered and concentrated to dryness, and dried under vacuum to give the crude product. The crude product was purified by silica gel column chromatography (Merck, 70 g) with EtOAc: hexane (1:9) as eluent to afford 3-bromo-1,3,4,5-tetrahydro-2H-1-benzazepin-2-one as an off-white solid (1.137 g, 70.1% yield, melting point 170-172 °C). The structure of the product was confirmed by 1H-NMR and 13C-NMR. TLC detection: Rf 0.13 (silica gel plate, EtOAc:hexane=1:4, observed under UV light).

References

[1] Patent: US6777550, 2004, B1. Location in patent: Page column 28
[2] Patent: US4575503, 1986, A
[3] Patent: US4410520, 1983, A
[4] Patent: US4473575, 1984, A
[5] Bioorganic and Medicinal Chemistry Letters, 2015, vol. 25, # 17, p. 3488 - 3494

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