2-p-Tolyl-4,5,6,7-tetrahydro-oxazolo[5,4-c]pyridine

Uses

5,6,7,8-Tetrahydro-1,6-naphthyridine is used in the synthetic preparation of quinolizidinone carboxylic acid selective M1 allosteric modulators.

Synthesis

6-Benzyl-5,6,7,8-tetrahydro-1,6-naphthyridine (3.9 g, 17.4 mmol) was used as a starting material and dissolved in 60 mL of acetic acid. A 0.4 g palladium/carbon catalyst was added. The reaction solution was transferred to a hydrogen reaction vessel and after three displacements with hydrogen, the reaction was carried out at 50 °C for 48 hours. After completion of the reaction, the catalyst was removed by filtration. The solvent was removed by distillation under reduced pressure and the resulting crude product was purified by column chromatography using a solvent mixture of dichloromethane and methanol (5:1, v/v) to afford the target product 5,6,7,8-tetrahydro-1,6-naphthyridine (1.48 g, 64% yield).

References

[1] Chemical and Pharmaceutical Bulletin, 1984, vol. 32, # 7, p. 2522 - 2529
[2] Patent: CN108250128, 2018, A. Location in patent: Paragraph 0638; 0640; 0643; 0644
[3] Patent: WO2009/56556, 2009, A1. Location in patent: Page/Page column 41
[4] Journal of Medicinal Chemistry, 2004, vol. 47, # 21, p. 5167 - 5182