Piperidine → HCID 178423280, compound

Participants

Reaction Conditions

Reaction Steps

Using the method described in Example 30 by employing 5-(3-chloro-4-fluorophenyl)-2-(1-pyrrolidinyl vinyl)furan (freshly prepared before use from 1-[5-(3-chloro-4-fluorophenyl)-2-furyl]ethan-1-one (Maybridge Chemical Company), pyrrolidine and TiCl4 (1.65 g, 5.67 mmol), 2-methyl-4,6-dichloro-5-nitropyrimidine (Example 76(b)) (1.20 g, 5.67 mmol), N,N-diisopropylethylamine (1.0 mL, 5.67 mmol), piperidine (0.9 mL, 9.1 mmol), NEt3 (1.0 mL) and SnCl2 (17 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 0.61 g (26%) of 5-(3-chloro-4-fluorophenyl)-2-[2-methyl-4-piperidylpyrrolo[4,5-d]pyrimidin-6-yl]furan as a beige colored solid. This compound (609 mg, 1.50 mmol) was dissolved in 10:1 EtOAc/MeOH (25 mL) and heated to boiling. To the hot solution was added 1 M ethereal HCl (1.50 mL, 1.50 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 385 mg (15%) of the title compound as tan colored small needles. Mp: >280° C. 1H NMR (DMSO-d6; 400 MHz): δ 1.65 (br s, 6), 2.51 (s, 3), 4.00 (br s, 4), 6.89 (s, 1), 7.26 (d, 1, J=3.7), 7.47 (d, 1, J=3.7), 7.50 (t, 1, J=9.0), 7.85-7.89 (m, 1), 8.10 (dd, 1, J=2.1, 7.1), 12.19 (s, 1), 14.31 (s, 1). MS m/z: 411 (M+1 for free base). Anal. Calcd for C22H20ClFN4O.HCl.1.5H2O: C, 55.70; H, 5.10; N, 11.81; Cl, 14.95. Found: C, 55.80; H, 5.10; N, 11.72; Cl, 15.06.

Provenance & Evidence