Uses
1,2,3,4-Tetrahydroquinolin-3-amine is used in the preparation of state-dependant NaV1.7 inhibitors for the treatment of neuropathic pain.
Synthesis
GENERAL METHOD: In a 1.5 mL reaction vial, tris(pentafluorophenyl)borane [B(C6F5)3] (0.025 mmol, 5.0 mol%) was dissolved in chloroform (0.60 mL), followed by the addition of diethylsilane (1.75 mmol, 3.5 equiv). After a short shaking, quinoline derivative (1a-p, 0.50 mmol, 1.0 eq.) was added to the above catalyst solution under argon protection. The reaction mixture was stirred at 25-65 °C for 6-24 h (for 1a-h) or at 25-100 °C for 2-24 h (for 1i-p) and subsequently cooled to room temperature. The reaction mixture was concentrated under reduced pressure to give the crude product. The crude product was treated with an ether solution (7 mL) of 0.25 N HCl and stirred at room temperature for 1 h to give a solid residue, which was subsequently washed with ether. The solid residue was dissolved or suspended in methanol (1.0 mL) and neutralized with sodium carbonate monohydrate (Na2CO3-H2O, 0.5 g) at 0 °C. After stirring for 2 h, methanol was removed under reduced pressure and the neutralized reaction residue was dissolved in dichloromethane (CH2Cl2) and washed sequentially with brine (5 mL) and water (5 mL). The crude product was isolated from the organic phase of the dichloromethane solution and finally purified by silica gel column chromatography using ethyl acetate/hexane (1:9 for 2a-h; 3:7 for 2i-p) as eluent to give the target product 2a-p.
References
[1] Synlett, 2017, vol. 28, # 18, p. 2396 - 2400
[2] Journal of Medicinal Chemistry, 1982, vol. 25, # 1, p. 68 - 70
[3] Patent: US5719141, 1998, A
