Piperidine → HCID 178423325, compound

HRID 1371213Notes

Reaction equation

HRID 1371213 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([CH:8]=[C:9]([N:11]2[CH2:15][CH2:14][CH2:13][CH2:12]2)[CH3:10])=[CH:4][CH:3]=1.[F:16][C:17]1[CH:22]=[CH:21][C:20]([CH2:23][C:24](=O)[CH3:25])=[CH:19][CH:18]=1.[NH:27]1[CH2:31]C[CH2:29][CH2:28]1.[CH3:32][C:33]1[N:38]=[C:37](Cl)[C:36]([N+:40]([O-])=O)=[C:35](Cl)[N:34]=1.[CH:44]([N:47](CC)C(C)C)([CH3:46])[CH3:45].[NH:53]1CCCC[CH2:54]1.Cl[Sn]Cl>CN(C=O)C.Cl[Ti](Cl)(Cl)Cl.CCN(CC)CC>[F:16][C:17]1[CH:22]=[CH:21][C:20]([CH2:23][CH:24]2[NH:11][CH:9]([CH3:10])[CH2:8][CH:32]([C:33]3[NH:38][C:37]4=[CH:28][CH:29]=[N:40][C:36]4=[CH:35][N:34]=3)[CH2:25]2)=[CH:19][CH:18]=1.[F:1][C:2]1[CH:3]=[CH:4][C:5]([C:8]2[CH:54]=[N:53][C:10]3[C:9]=2[NH:11][C:15]([CH:14]2[CH2:13][CH:12]([CH3:32])[NH:47][CH:44]([CH3:45])[CH2:46]2)=[N:27][CH:31]=3)=[CH:6][CH:7]=1

Participants

12

Reactant 7

HCID 8082PiperidineHCID 24479Stannous Chloride2×HCID 31268PyrrolidineHCID 81531DiisopropylethylamineHCID 831924,6-Dichloro-2-methyl-5-nitropyrimidineHCID 521187(4-Fluorophenyl)acetoneHCID 53810138HCID 53810138, compound

Product 2

HCID 178423320HCID 178423320, compoundYield 4%HCID 178423325HCID 178423325, compoundYield 7%

Reagents, catalysts & solvents 3

HCID 24193Titanium TetrachlorideCatalystHCID 6228DimethylformamideSolventHCID 8471TriethylamineSolvent

Conditions

Temperature
140 °C

Procedure

Using the method described in Example 30 by employing [2-(4-fluorophenyl)-1-methylvinyl]pyrrolidine (freshly prepared before use from (4-fluorophenyl) acetone (Aldrich Chemical Company), pyrrolidine and TiCl4 (1.64 g, 8.00 mmol), 2-methyl-4,6-dichloro-5-nitropyrimidine (Example 76(b)) (1.66 g, 8.00 mmol), N,N-diisopropylethylamine (1.4 mL, 8.00 mmol), piperidine (1.3 mL, 12.8 mmol), NEt3 (1.8 mL) and SnCl2 (24 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 108 g (4%) of 6-[(4-fluorophenyl)methyl]-2-methyl-4-piperidylpyrrolo[3,2-d]pyrimidine as a white colored solid and 172 mg (7%) of 7-(4-fluorophenyl)-2,6-dimethyl-4-piperidylpyrrolo[3,2-d]pyrimidine as a white 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-4f64cc4f1c104d539fbd2507d2d22077
Source dataset
uspto-grants-2003_06
Patent number
US06583154B1

Reaction notes

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