Piperidine → HCID 178423289, compound

HRID 1371208Notes

Reaction equation

HRID 1371208 reaction equation
[N:1]1([C:6]([C:8]2[CH:9]=[N:10][CH:11]=[CH:12][CH:13]=2)=[CH2:7])[CH2:5][CH2:4]CC1.C(C1C=NC=CC=1)(=O)C.N1CCCC1.[CH3:28][C:29]1[N:34]=C(Cl)C([N+]([O-])=O)=[C:31](Cl)[N:30]=1.C([N:43]([CH2:47][CH3:48])[CH:44]([CH3:46])[CH3:45])(C)C.N1CCCCC1.Cl[Sn]Cl>CN(C=O)C.Cl[Ti](Cl)(Cl)Cl.CCN(CC)CC>[CH3:46][CH:44]1[CH2:45][CH:28]([C:29]2[NH:34][C:4]3=[CH:7][C:6]([C:8]4[CH:9]=[N:10][CH:11]=[CH:12][CH:13]=4)=[N:1][C:5]3=[CH:31][N:30]=2)[CH2:48][CH2:47][NH:43]1

Participants

11

Reactant 7

HCID 8082PiperidineHCID 95893-AcetylpyridineHCID 24479Stannous Chloride2×HCID 31268PyrrolidineHCID 81531DiisopropylethylamineHCID 831924,6-Dichloro-2-methyl-5-nitropyrimidineHCID 18511064HCID 18511064, compound

Product 1

HCID 178423289HCID 178423289, compoundYield 3%

Reagents, catalysts & solvents 3

HCID 24193Titanium TetrachlorideCatalystHCID 6228DimethylformamideSolventHCID 8471TriethylamineSolvent

Conditions

Temperature
140 °C

Procedure

Using the method described in Example 30 by employing 3-(1-pyrrolidinylvinyl)pyridine (freshly prepared before use from 3-acetylpyridine (Aldrich Chemical Company), pyrrolidine and TiCl4 (1.95 g, 11.2 mmol), 2-methyl-4,6-dichloro-5-nitropyrimidine (Example 76(b)) (2.32 g, 11.2 mmol), N,N-diisopropylethylamine (2.0 mL, 11.2 mmol), piperidine (1.8 mL, 17.9 mmol), NEt3 (2.5 mL) and SnCl2 (34 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 0.5 h then the heating was discontinued and the mixture was allowed to cool to room temperature. The mixture was stirred at room temperature an additional 4 d. The residue was purified by flash chromatography on silica gel with 95:5 CHCl3/MeOH as eluant to give 0.90 mg (3%) of 2-methyl-4-piperidyl-6-(3-pyridyl)pyrrolo[3,2-d]pyrimidine as a beige colored solid. This compound (89 mg, 0.30 mmol) was dissolved in 10:1 EtOAc/MeOH (10 mL) and heated to boiling. To the hot solution was added 1 M ethereal HCl (0.30 mL, 0.30 mmol). The solution was allowed to cool to room temperature. The resulting crystals were collected by filtration, washed with EtOAc (2×5 mL), Et2O (3×5 mL) and dried under vacuum at 60° C. to give 54 mg (2%) of the title compound as a brown colored solid. Mp: >280° C. 1H NMR (DMSO-d6; 500 MHz): δ 1.65 (br s, 6), 2.51 (s, 3), 4.02 (t, 4, J=5.4), 6.96 (s, 1), 7.52 (dd, 1, J=7.9, 7.9), 8.32 (d, 1, J=8.0), 8.61 (d, 1, J=4.8), 9.11 (d, 1, J=2.1), 12.08 (s, 1), 14.29 (s, 1). MS m/z: 294 (M+1 for free base). Anal. Calcd for C17H19N5.1.05HCl.1.5H2O: C, 56.90; H, 6.48; N, 19.52; Cl, 10.37. Found: C, 57.20; H, 6.23; N, 19.50; Cl, 10.39.

Workup

  1. customwas added to the reaction mixture at 140° C
  2. temperatureto cool to room temperature
  3. stirringThe mixture was stirred at room temperature an additional 4 d
  4. customThe residue was purified by flash chromatography on silica gel with 95:5 CHCl3/MeOH as eluant

Sources & evidence

ORD record
ord-7de4eed198ad4297a777f306bfb4c2c6
Source dataset
uspto-grants-2003_06
Patent number
US06583154B1

Reaction notes

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