8,9-Dihydro-5H-benzo[7]annulen-7(6H)-one

Uses

8,9-Dihydro-5H-benzo[7]annulen-7(6H)-one is a reactant in the preparation of benzo[7]annulen-7-amines with GluN2B affinity and selectivity.

Synthesis

The general procedure for the synthesis of 8,9-dihydro-5H-benzo[7]roten-7(6H)-ones from the compound (CAS:24790-66-7) was as follows: first, 3 5,6,8,9-tetrahydro-benzocyclohepten-7-one (compound of formula II) was prepared. A mixture of isomers of dimethyl 7-oxo-5,6,8,9-tetrahydrobenzocycloheptene-6,8-dicarboxylate (80 g, obtained according to Preparation 2) was dissolved in a mixture of aqueous 3M sulfuric acid (300 mL) and acetonitrile (50 mL) under argon protection and refluxed overnight. Upon completion of the reaction, the mixture was diluted with ether, neutralized with 2M aqueous sodium hydroxide solution (3 x 300 mL), subsequently dried with magnesium sulfate and evaporated to dryness. The residue was distilled at 97-98 °C, 0.4-0.5 Torr to give colorless crystals (26.1 g, 84% yield, α,α'-dibromo-o xylene). The melting point of the product was 43-44 °C. The 1H-NMR (CDCl3) data were as follows: 7.23 (m, 4H, aromatic hydrogen); 2.91 (m, 2H, hydrogen in the C(6) and C(8) positions); 2.62 (m, 2H, hydrogen in the C(5) and C(9) positions).

References

[1] Patent: US2010/69504, 2010, A1. Location in patent: Page/Page column 5
[2] Bioorganic and Medicinal Chemistry, 2014, vol. 22, # 23, p. 6638 - 6646
[3] Patent: WO2008/83367, 2008, A2. Location in patent: Page/Page column 132-133
[4] Patent: WO2010/5876, 2010, A2. Location in patent: Page/Page column 55-56
[5] Drugs of the Future, 2018, vol. 43, # 9, p. 645 - 653