Piperidine → HCID 178423317、化合物

Using the method described in Example 30 by employing [1-(3,5-difluorophenyl)vinyl]pyrrolidine (freshly prepared before use from 3,5-difluoro acetophenone (Oakwood Products Inc.), pyrrolidine and TiCl4 (1.32 g, 6.32 mmol), 2-methyl-4,6-dichloro-5-nitropyrimidine (Example 76(b)) (1.30 g, 6.32 mmol), N,N-diisopropylethylamine (1.1 mL, 6.32 mmol), piperidine (1.0 mL, 10.1 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 820 mg (40%) of 6-(3,5-difluorophenyl)-2-methyl-4-piperidylpyrrolo[3,2-d]pyrimidine as a brown colored gummy solid. This compound (820 mg, 2.52 mmol) was dissolved in 5:1 EtOAc/MeOH (40 mL) and heated to boiling. To the hot solution was added 1 M ethereal HCl (2.50 mL, 2.50 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 440 mg (19%) of the title compound as pale yellow colored needles. Mp: >280° C. 1H NMR (DMSO-d6; 500 MHz): δ 1.61 (br s, 6), 2.47 (s, 3), 3.97 (br s, 4), 6.97 (s, 1), 7.28 (tt, 1, J=2.1, 7.1), 7.74 (d, 2, J=6.6), 11.93 (s, 1), 14.35 (s, 1). MS m/z: 329 (M+1 for free base). Anal. Calcd for C18H18F2N4.HCl.H2O: C, 56.47; H, 5.53; N, 14.64; Cl, 9.26. Found: C, 56.52; H, 5.54; N, 14.74; Cl, 9.38.

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レコード

ord-3ae531b9b42f4cc2b994e480cd86bf3f

出典データセット

uspto-grants-2001_02

DOI

10.6084/m9.figshare.5104873.v1

特許番号

US06187777B1