Hydrochloric Acid → 2-[1-(9,10-Dihydro-9,10-methanoanthracen-9-ylmethyl)-4-piperidylamino]pyrimidine

Participants

Reaction Steps

9-Formyl-9,10-dihydro-9,10-methanoanthracene (0.683 g, 3.1 mmol) was stirred for 1 hour at room temperature in methanol (7.0 mL) with 2-(4-piperidylamino)pyrimidine hydrochloride (1.000 g, 4.7 mmol, prepared as described below) and activated, powdered, 3 angstrom molecular sieves (0.820 g). The pH was initially adjusted to 6.5 with methanolic hydrogen chloride. Sodium cyanoborohydride (0.137 g, 2.2 mmol) was added and the tan suspension stirred for 23 hours. The suspension was poured into strongly basic (NaOH) brine solution (pH>11) and extracted with methylene chloride. The combined extracts were dried (sodium sulfate) and concentrated to give the crude product. Flash chromatography on silica gel using 15% acetone/hexanes provided the title compound as a white solid (0.225 g, 0.6 mmol, 20%). Using a procedure similar to that described in Example 87, the hydrochloride salt was obtained, mp 290° C. (dec); MS(CI): 456 (M+H); NMR (250 MHz, DMSO-d6): 9.87(br m, 1H), 8.38-8.32(m, 2H), 7.64(br m, 1H), 7.37-7.31(m, 4H), 7.03-6.94(m, 4H), 6.70-6.63(m, 1H), 4.46(s, 1H), 4.34-4.32(m, 2H), 4.16(br m, 1H), 3.60-3.34(m, 4H), 2.73(s, 2 H), 2.11-1.88(m, 4H).

Provenance & Evidence