Piperidine → HCID 178423285, compound

HRID 635710Notes

Reaction equation

HRID 635710 reaction equation
[Cl:1][C:2]1[C:7]([Cl:8])=[C:6]([Cl:9])[CH:5]=[CH:4][C:3]=1[C:10]([N:12]1[CH2:16][CH2:15]CC1)=[CH2:11].ClC1C(Cl)=C(Cl)C=CC=1C(=O)C.N1CCCC1.[CH3:34][C:35]1[N:40]=C(Cl)C([N+]([O-])=O)=[C:37](Cl)[N:36]=1.C([N:49]([CH2:53][CH3:54])[CH:50]([CH3:52])[CH3:51])(C)C.N1CCCCC1.Cl[Sn]Cl>CN(C=O)C.Cl[Ti](Cl)(Cl)Cl.CCN(CC)CC>[CH3:52][CH:50]1[CH2:51][CH:34]([C:35]2[NH:40][C:15]3=[CH:11][C:10]([C:3]4[CH:4]=[CH:5][C:6]([Cl:9])=[C:7]([Cl:8])[C:2]=4[Cl:1])=[N:12][C:16]3=[CH:37][N:36]=2)[CH2:54][CH2:53][NH:49]1

Participants

11

Reactant 7

HCID 8082PiperidineHCID 24479Stannous ChlorideHCID 261322',3',4'-TrichloroacetophenoneHCID 31268PyrrolidineHCID 81531DiisopropylethylamineHCID 831924,6-Dichloro-2-methyl-5-nitropyrimidineHCID 18511385HCID 18511385, compound

Product 1

HCID 178423285HCID 178423285, compoundYield 9%

Reagents, catalysts & solvents 3

HCID 24193Titanium TetrachlorideCatalystHCID 6228DimethylformamideSolventHCID 8471TriethylamineSolvent

Procedure

Using the method described in Example 30 by employing [1-(2,3,4-trichlorophenyl]vinyl]pyrrolidine (freshly prepared before use from 2′,3′,4′-trichloro acetophenone (Aldrich Chemical Company), pyrrolidine and TiCl4 (1.00 g, 3.64 mmol), 2-methyl-4,6-dichloro-5-nitropyrimidine (Example 76(b)) (0.80 g, 3.64 mmol), N,N-diisopropylethylamine (0.6 mL, 3.64 mmol), piperidine (0.6 mL, 5.80 mmol), NEt3 (0.7 mL) and SnCl2 (11 mL of a 2 M soln in DMF). The residue was purified by flash chromatography on silica gel with 95:5 CHCl3/MeOH as eluant to give 125 mg (9%) of 2-methyl-4-piperidyl-6-(2,3,4-trichlorophenyl)pyrrolo[3,2-d]pyrimidine as a brown colored oil. This material (125 mg, 0.32 mmol) was dissolved in 5:1 EtOAc/MeOH (15 mL) and heated to boiling. To the hot solution was added 1 M ethereal HCl (0.40 mL, 0.40 mmol). The solution was left 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 55 mg (4%) of the title compound as beige colored needles. Mp: 264-266° C. 1H NMR (DMSO-d6; 400 MHz): δ 1.71 (br s, 6), 2.58 (s, 3), 4.03 (s, 4), 6.78 (s, 1), 7.71 (d, 2, J=8.4), 7.88 (d, 2, J=8.5), 12.40 (s, 1), 14.39 (s, 1). MS m/z: 396 (M+1 for free base). Anal. Calcd for C18H17Cl3N4.HCl.1.75H2O: C, 46.59; H, 4.67; N, 12.09; Cl, 30.59. Found: C, 46.64; H, 4.60; N, 11.93; Cl, 30.48.

Workup

  1. customThe residue was purified by flash chromatography on silica gel with 95:5 CHCl3/MeOH as eluant

Sources & evidence

ORD record
ord-bc2758eb1cff47699284f4ba1e65b0d8
Source dataset
uspto-grants-2001_02
Patent number
US06187777B1

Reaction notes

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