Uses
6-Methoxy-1,2,3,4-tetrahydroisoquinoline is used in the synthesis of novel spirobicyclic Artemisinin (A777500) analogues for anti-tumor activity.
Synthesis
6.1.18 Synthesis of 6-methoxy-1,2,3,4-tetrahydroisoquinoline (35): to an anhydrous tetrahydrofuran (THF, 20 mL) solution of 6-(methoxy)-3,4-dihydro-1(2H)-isoquinolone (34, 1.4 g, 7.9 mmol) was added slowly under nitrogen protection lithium aluminum hydride (LiAlH4, 601 mg, 15.8 mmol). The reaction mixture was stirred at 60 °C overnight. Upon completion of the reaction, it was cooled to room temperature and the reaction was quenched by sequential addition of water (0.6 mL) and 15% sodium hydroxide (NaOH) solution (0.6 mL), and stirring was continued for 30 minutes. The reaction mixture was filtered and the filtrate was concentrated under reduced pressure. The resulting residue was purified by silica gel column chromatography (eluent: dichloromethane/methanol=20:1) to afford the target product 35 (1.06 g, 77% yield) as a yellow oil.1H NMR (400 MHz, CDCl3): δ 6.94 (d, J=8.0 Hz, 1H), 6.71 (d, J=8.0 Hz, 1H), 6.63 (s 1H), 4.00 (s, 2H), 3.78 (s, 3H), 3.16 (t, J=5.6Hz, 2H), 2.83 (t, J=5.2Hz, 2H).
References
[1] Journal of Medicinal Chemistry, 1987, vol. 30, # 12, p. 2208 - 2216
[2] Indian Journal of Chemistry, Section B: Organic Chemistry Including Medicinal Chemistry, 1993, vol. 32, # 12, p. 1209 - 1213
[3] Bioorganic and Medicinal Chemistry, 2016, vol. 24, # 2, p. 207 - 219
[4] Bioorganic and Medicinal Chemistry, 2016, vol. 24, # 4, p. 789 - 801
[5] Bioorganic and Medicinal Chemistry, 2015, vol. 23, # 21, p. 6855 - 6868
