1,2,3,4-Tetrahydroisoquinoline → 2-(1-Acetyl-6-fluoro-1H-indazol-3-ylmethyl)-1,2,3,4-tetrahydroisoquinoline

Participants

Reaction Conditions

Reaction Steps

1-Acetyl-3-bromomethyl-6-fluoro-1H-indazole (0.53 g, 1.96 mmol) in CH2Cl2 (10 mL) was treated with 1,2,3,4-tetrahydroisoquinoline (0.261 g, 1.96 mmol) and Hunig's base (0.44 mL, 2.5 mmol) and the mixture stirred at 20° C. for 16 h. The mixture was poured into saturated aqueous sodium bicarbonate solution (25 mL) and extracted with CH2Cl2 (3×25 mL). The combined organic extracts were dried (MgSO4), concentrated and the residue purified by flash chromatography (7%→12% EtOAc in hexane) to give the title compound as a white solid (475 mg, 53%); mp 106°-107° C. (from Et2O/hexane); 1H NMR (360 MHz, d6 -DMSO) δ 8.08 (dd, J=8.8, 5.4 Hz, 1H, indazole), 8.00 (dd, J=9.6, 2.2 Hz, 1H, indazole), 7.29 (dt, J=9.1, 2.5 Hz, 1H, indazole), 7.10 (m, 3H, tetrahydroisoquinoline), 7.02 (m, 1H, tetrahydroisoquinoline), 4.05 (s, 2H, Ar--CH2N), 3.68 (s, 2H, Ar--CH2N)), 2.79 (m, 4H, tetrahydroisoquinoline)2.72 (s, 3H, Ac); MS (CI+) m/e 324 (M+H+); Anal. calcd for C19H18FN3O: C, 70.57; H, 5.61; N, 12.99. Found: C, 70.28; H, 5.32; N, 12.84.

Provenance & Evidence