Piperidine → HCID 178489658, compound

HRID 1371207Notes

Reaction equation

HRID 1371207 reaction equation
[N:1]1([C:6]([CH3:16])=[CH:7][C:8]2[CH:13]=[CH:12][C:11]([O:14][CH3:15])=[CH:10][CH:9]=2)[CH2:5][CH2:4][CH2:3][CH2:2]1.COC1C=CC(CC(=O)C)=CC=1.[NH:29]1[CH2:33]CCC1.[CH3:34][C:35]1[N:40]=[C:39](Cl)[C:38]([N+:42]([O-])=O)=[C:37](Cl)[N:36]=1.[CH:46]([N:49]([CH2:53][CH3:54])[CH:50]([CH3:52])[CH3:51])(C)C.[NH:55]1CCCC[CH2:56]1.Cl[Sn]Cl>CN(C=O)C.Cl[Ti](Cl)(Cl)Cl.CCN(CC)CC>[CH3:15][O:14][C:11]1[CH:10]=[CH:9][C:8]([CH2:7][C:6]2[CH:16]=[C:4]3[NH:40][C:35]([CH:34]4[CH2:54][CH2:53][NH:49][CH:50]([CH3:51])[CH2:52]4)=[N:36][CH:37]=[C:5]3[N:1]=2)=[CH:13][CH:12]=1.[CH3:46][CH:2]1[CH2:3][CH:4]([C:5]2[NH:1][C:6]3=[C:7]([C:8]4[CH:9]=[CH:10][C:11]([O:14][CH3:15])=[CH:12][CH:13]=4)[CH:33]=[N:29][C:16]3=[CH:56][N:55]=2)[CH2:39][CH:38]([CH3:37])[NH:42]1

Participants

12

Reactant 7

HCID 8082PiperidineHCID 24479Stannous Chloride2×HCID 312311-(p-Methoxyphenyl)-2-propanoneHCID 31268PyrrolidineHCID 81531DiisopropylethylamineHCID 831924,6-Dichloro-2-methyl-5-nitropyrimidineHCID 57145574HCID 57145574, compound

Product 2

HCID 178488740HCID 178488740, compoundYield 10%HCID 178489658HCID 178489658, compoundYield 12%

Reagents, catalysts & solvents 3

HCID 24193Titanium TetrachlorideCatalystHCID 6228DimethylformamideSolventHCID 8471TriethylamineSolvent

Conditions

Temperature
140 °C

Procedure

Using the method described in Example 30 by employing 1-[2-pyrrolidinylprop-1-enyl]-4-methoxy benzene (freshly prepared before use from 4-methoxy phenylacetone (Aldrich Chemical Company), pyrrolidine and TiCl4 (3.06 g, 14.10 mmol), 2-methyl-4,6-dichloro-5-nitropyrimidine (Example 76(b)) (2.92 g, 14.10 mmol), N,N-diisopropylethylamine (2.5 mL, 14.10 mmol), piperidine (2.2 mL, 22.6 mmol), NEt3 (3.1 mL) and SnCl2. (42 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 50:50 EtOAc/hexanes as eluant to give 578 g (12%) of 4-methoxy-1-[(2-methyl-4-piperidylpyrrolo[4,5-d]pyrimidin-6-yl)methyl]benzene as a brown colored solid and 466 mg (10%) of 1-[2,6-dimethyl-4-piperidylpyrrolo[3,2-d]pyrimidin-7-yl]-4-methoxybenzene as a beige colored solid.

Workup

  1. customwas added to the reaction mixture at 140° C
  2. temperatureto cool to room temperature
  3. customThe residue was purified by flash chromatography on silica gel with 50:50 EtOAc/hexanes as eluant

Sources & evidence

ORD record
ord-e7f48f64a269482297dd34018da9efd6
Source dataset
uspto-grants-2003_06
Patent number
US06583154B1

Reaction notes

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