Piperidine → HCID 178432690, compound

Using the method described in Example 30 by employing 2,4-dimethyl-5-(1-pyrrolidinylvinyl)-1,3-thiazole (freshly prepared before use from 5-acetyl-2,4-dimethylthiazole (Acros Chemical Company), pyrrolidine and TiCl4 (1.35 g, 6.45 mmol), 2-methyl-4,6-dichloro-5-nitropyrimidine (Example 76(b)) (1.32 g, 6.45 mmol), N,N-diisopropylethylamine (1.1 mL, 6.45 mmol), piperidine (1.0 mL, 10.3 mmol), NEt3 (1.1 mL) and SnCl2 (19 mL of a 2 M soln in DMF). In this example the 2 M SnCl2 solution was added to the reaction mixture at 140° C. Heating was then discontinued and the mixture was allowed to cool to room temperature. The mixture was stirred at room temperature for an additional 48 h. The residue was purified by flash chromatography on silica gel with 95:5 CHCl3/MeOH as eluant to give 356 mg (17%) of 2,4-dimethyl-5-[2-methyl-4-piperidylpyrrolo[4,5-d]pyrimidin-6-yl]-1,3-thiazole as a beige colored solid. This compound (356 mg, 1.10 mmol) was dissolved in 4:1 EtOAc/MeOH (20 mL) and heated to boiling. To the hot solution was added 1 M ethereal HCl (1.10 mL, 1.10 mmol). The solution was allowed to cool to room temperature. The resulting solid was collected by filtration, washed with EtOAc (2×10 mL), Et2O (3×15 mL) and dried under vacuum at 60° C. to give 332 mg (16%) of the title compound as a cream colored solid. Mp: 272-273.5° C. 1H HMR (DMSO-d6; 500 MHz): δ 1.63 (br d, 6, J=5.4), 2.37 (s, 3), 2.50 (s, 3), 2.62 (s, 3), 3.96 (br t, 4, J=4.7), 6.56 (s, 1), 12.22 (s, 1), 14.44 (s, 1). MS m/z: 328 (M+1 for free base). Anal. Calcd for C17H21N5S.1.2HCl.1.5H2O: C, 51.27; H, 6.38; N, 5 17.59; Cl, 1041. Found: C, 51.59; H, 6.35; N, 17.48; Cl, 10.68.

1. customwas added to the reaction mixture at 140° C
2. temperatureHeating
3. customThe residue was purified by flash chromatography on silica gel with 95:5 CHCl3/MeOH as eluant

ORD record

ord-8b6b5ed1ca7b4eb9abbc7a20dd8e758f

Source dataset

uspto-grants-2003_06

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06583154B1