Piperidine → HCID 178423315, compound

HRID 1371176Notes

Reaction equation

HRID 1371176 reaction equation
FC1C=[C:4]([C:9]([N:11]2CCCC2)=[CH2:10])C=CC=1F.[F:16][C:17]1[CH:18]=[C:19]([C:24](=O)[CH3:25])[CH:20]=[CH:21][C:22]=1[F:23].N1CC[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.C(N(CC)C(C)C)(C)C.N1CCCCC1.Cl[Sn]Cl>CN(C=O)C.Cl[Ti](Cl)(Cl)Cl.CCN(CC)CC>[F:16][C:17]1[CH:18]=[C:19]([CH:24]2[NH:11][CH:9]([CH3:10])[CH2:4][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:20]=[CH:21][C:22]=1[F:23]

Participants

11

Reactant 7

HCID 8082PiperidineHCID 24479Stannous ChlorideHCID 31268PyrrolidineHCID 81531DiisopropylethylamineHCID 831924,6-Dichloro-2-methyl-5-nitropyrimidineHCID 1230521-(3,4-Difluorophenyl)ethan-1-oneHCID 18511122HCID 18511122, compound

Product 1

HCID 178423315HCID 178423315, compoundYield 18%

Reagents, catalysts & solvents 3

HCID 24193Titanium TetrachlorideCatalystHCID 6228DimethylformamideSolventHCID 8471TriethylamineSolvent

Procedure

Using the method described in Example 30 by employing [1-(3,4-difluorophenyl)vinyl]pyrrolidine (freshly prepared before use from 3′,4′-difluoro acetophenone (Aldrich Chemical Company), pyrrolidine and TiCl4 (1.38 g, 6.60 mmol), 2-methyl-4,6-dichloro-5-nitropyrimidine (Example 76(b)) (1.40 g, 6.60 mmol), N,N-diisopropylethylamine (1.1 mL, 6.60 mmol), piperidine (1.0 mL, 10.6 mmol), NEt3 (1.1 mL) and SnCl2 (20 mL of a 2 M soln in DMF). The residue was purified by flash chromatography on silica gel with 95:5 HCl3/MeOH as eluant to give 395 mg (18%) of 6-(3,4-difluorophenyl)-2-methyl-4-piperidylpyrrolo[3,2-d]pyrimidine as a beige colored solid. This material (395 mg, 1.20 mmol) was dissolved in 10:1 EtOAc/MeOH (40 mL) and heated to boiling. To the hot solution was added 1 M ethereal HCl (1.20 mL, 1.20 mmol). The solution was left to cool to room temperature. The resulting solid was collected by filtration, washed with EtOAc (2×10 mL), Et2O (3×15 mL) and dried under vacuum at 60° C. to give 159 mg (6%) of the title compound as beige colored solid. Mp: 243-245° C. 1H NMR (DMSO-d6; 500 MHz): δ 1.71 (br s, 6), 2.57 (s, 3), 4.06 (t, 4, J=5.0), 6.85 (s, 1), 7.63 (q, 1, J=10.0), 7.89 (d, 1, J=8.1), 8.19 (dt, 1, J=1.3, 9.5), 12.01 (s, 1), 14.39 (s, 1). MS m/z: 329 (M+1 for free base). Anal. Calcd for C18H18F2N4.HCl.1.25H2O: C, 55.81; H, 5.60; N, 14.47; Cl, 9.15. Found: C, 55.95; H, 5.25; N, 14.62; Cl, 9.26.

Workup

  1. customThe residue was purified by flash chromatography on silica gel with 95:5 HCl3/MeOH as eluant

Sources & evidence

ORD record
ord-86de394935524960ba8e120df3026e67
Source dataset
uspto-grants-2003_06
Patent number
US06583154B1

Reaction notes

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