Diisopropylethylamine → 1-acetyl-3-(4-phenethylpiperidin-1-ylmethyl)-1H-indazole

Participants

Reaction Conditions

Reaction Steps

1-Acetyl-3-bromomethyl-1H-indazole (0.50 g, 1.98 mmol) in CH2Cl2 (25 mL) was treated with 4-phenethylpiperidine hydrochloride (0.893 g, 3.96 mmol) and Hunig's base (0.78 g, 5.94 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 (0%→10% EtOAc in hexane) to give 1-acetyl-3-(4-phenethylpiperidin-1-ylmethyl)-1H-indazole as a colourless oil (98 mg, 14%). This was dissolved in CH2Cl2 /methanol (1:1, 10 mL), treated with NaOMe (2 mg) and stirred for 15 min at 20° C. 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 recrystallised from EtOAc/hexane to give the title compound (55 mg, 69%) as colourless crystals; mp 153°-155° C. (from EtOAc/hexane); 1H NMR (360 MHz, d6 -DMSO) δ 12.75 (bs, 1H, NH), 7.84 (d, J=8.1 Hz, 1H, indazole), 7.46 (d, J=8.4 Hz, 1H, indazole), 7.31 (t, J=6.7 Hz, 1H, indazole), 7.27-7.12 (m, 5H, Ph), 7.07 (t, J=7.1 Hz, 1H, indazole), 3.78 (s, 2 H, Ar--CH2N), 2.85 (m, 2 H, aliphatic), 2.56 (m, 2 H, aliphatic), 1.94 (m, 2H, aliphatic), 1.65 (m, 2H, aliphatic), 1.47 (m, 2H, aliphatic), 1.16 (m, 3H, aliphatic); MS (CI+) m/e 320 (M+H+); Anal. calcd for C21H25N3 : C, 78.96; H, 7.89; N, 13.15. Found: C, 78.94; H, 7.96; N, 12.89.

Provenance & Evidence