7-Dimethoxymethyl-1,2,3,4-tetrahydro-[1,8]naphthyridine

Synthesis

General procedure for the synthesis of 7-dimethoxymethyl-1,2,3,4-tetrahydro[1,8]naphthyridine from [1,8]naphthyridine-2-carboxaldehyde dimethanol: A solution of [1,8]naphthyridine-2-carboxaldehyde dimethanol (20.0 g, 97.9 mmol) in ethanol (400 mL) was hydrogenated catalytically by PtO2 (778 mg) in a hydrogen atmosphere at room temperature and at 1 atmosphere pressure for 18 hours. Upon completion of the reaction, the reaction mixture was filtered through Solka Floc and washed with ethanol-water (1:2, v/v) mixture. The filtrate and washings were combined and concentrated under reduced pressure to remove ethanol. During concentration, the product gradually crystallized. The crystals were collected by filtration and dried under reduced pressure to afford 7-dimethoxymethyl-1,2,3,4-tetrahydro[1,8]naphthyridine (18.7 g, 92% yield) with a melting point of 91-92.5 °C.1H NMR (300 MHz, CDCl3): δ 7.08 (d, J = 7.4 Hz, 1H), 6.62 (d, J = 7.4 Hz, 1H), 5.07 ( s, 2H; 1H exchangeable with D2O), 3.37-3.29 (m, 2H), 3.29 (s, 6H), 2.64 (t, J = 6.3 Hz, 2H), 1.86-1.78 (m, 2H).13C NMR (75.5 MHz, CDCl3): δ 155.9, 153.0, 136.3, 116.0, 109.8 , 103.9, 53.3, 41.5, 26.6, 21.2.

References

[1] The Journal of organic chemistry, 2004, vol. 69, # 6, p. 1959 - 1966
[2] Patent: WO2016/154369, 2016, A1. Location in patent: Page/Page column 19
[3] Patent: US2008/269225, 2008, A1. Location in patent: Page/Page column 37-38
[4] Patent: US2003/229079, 2003, A1. Location in patent: Page 36
[5] Patent: WO2007/79214, 2007, A2. Location in patent: Page/Page column 102