Piperidine → HCID 178421818, compound

Participants

Reaction Conditions

Reaction Steps

Using the method described in Example 30 by employing 3-methyl-2-(1-pyrrolidinylvinyl)benzo[b]thiophene (freshly prepared before use from 2-acetyl-3-methylthianaphthene (Avocado Chemical Company), pyrrolidine and TiCl4 (1.67 g, 6.88 mmol), 2-methyl-4,6-dichloro-5-nitropyrimidine (Example 76(b)) (1.43 g, 6.88 mmol), N,N-diisopropylethylamine (1.2 mL, 6.88 mmol), piperidine (1.1 mL, 11.0 mmol), NEt3 (1.5 mL) and SnCl2 (21 mL of a 2 M soln in DMF). In this example the SnCl2 solution was added to the reaction mixture at 140° C. The mixture was stirred at 140° C. for an additional 16 h then the heating was discontinued and the mixture was allowed to cool to room temperature. The residue was purified by flash chromatography on silica gel with 95:5 CHCl3/MeOH as eluant to give 0.60 g (24%) of 3-methyl-2-[2-methyl-4-piperidylpyrrolo[4,5-d]pyrimidin-6-yl]benzo[b]thiophene as a beige colored solid. This compound (596 mg, 1.64 mmol) was dissolved in 5:1 EtOAc/MeOH (30 mL) and heated to boiling. To the hot solution was added 1 M ethereal HCl (1.70 mL, 1.70 mmol). The solution was allowed to cool to room temperature. The resulting crystals were collected by filtration, washed with EtOAc (2×10 mL), Et2O (3×15 mL) and dried under vacuum at 60° C. to give 421 mg (16%) of the title compound as a pale yellow colored powder. Mp: >280° C. 1H NMR (DMSO-d6; 400 MHz): δ 1.65 (br s, 6), 2.46 (s, 3), 2.51 (s, 3), 3.98 (br s, 4), 6.67 (s, 1), 7.41-7.47 (m, 2), 7.87 (dd, 1, J=1.7, 6.2), 7.99 (dd, 1, J=1.7, 6.4), 12.43 (s, 1), 14.38 (s, 1). MS m/z: 363 (M+1 for free base). Anal. Calcd for C21H22N4S.HCl.0.4H2O: C, 62.10; H, 5.91; N, 13.80; Cl, 8.73. Found: C, 62.04; H, 5.92; N, 13.80; Cl, 8.83.

Provenance & Evidence