Piperidine → HCID 178423318, compound

HRID 1371165Notes

Reaction equation

HRID 1371165 reaction equation
FC1C=CC=C(F)[C:3]=1[C:9]([N:11]1CCCC1)=[CH2:10].[F:16][C:17]1[CH:22]=[CH:21][CH:20]=[C:19]([F:23])[C:18]=1[C:24](=O)[CH3:25].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:22]=[CH:21][CH:20]=[C:19]([F:23])[C:18]=1[CH:24]1[NH:11][CH:9]([CH3:10])[CH2:3][CH:32]([C:33]2[NH:38][C:37]3=[CH:28][CH:29]=[N:40][C:36]3=[CH:35][N:34]=2)[CH2:25]1

Participants

11

Reactant 7

HCID 8082PiperidineHCID 24479Stannous ChlorideHCID 31268PyrrolidineHCID 81531DiisopropylethylamineHCID 831924,6-Dichloro-2-methyl-5-nitropyrimidineHCID 836431-(2,6-Difluorophenyl)ethan-1-oneHCID 18511326HCID 18511326, compound

Product 1

HCID 178423318HCID 178423318, compoundYield 11%

Reagents, catalysts & solvents 3

HCID 24193Titanium TetrachlorideCatalystHCID 6228DimethylformamideSolventHCID 8471TriethylamineSolvent

Procedure

Using the method described in Example 30 by employing [1-(2,6-difluorophenyl)vinyl]pyrrolidine (freshly prepared before use from 2′,6′-difluoro acetophenone (Aldrich Chemical Company), pyrrolidine and TiCl4 (1.51 g, 7.22 mmol), 2-methyl-4,6-dichloro-5-nitropyrimidine (Example 76(b)) (1.20 g, 5.79 mmol), N,N-diisopropylethylamine (1.3 mL, 7.22 mmol), piperidine (1.2 mL, 11.6 mmol), NEt3 (1.2 mL) and SnCl2 (22 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 199 mg (11%) of 6-(2,6-difluorophenyl)-2-methyl-4-piperidylpyrrolo[3,2-d]pyrimidine as a beige colored powder. This material (199 mg, 0.61 mmol) was dissolved in 5:1 EtOAc/MeOH (20 mL) and heated to boiling. To the hot solution was added 1 M ethereal HCl (0.60 mL, 0.60 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 33 mg (2%) of the title compound as a pale yellow colored sandy solid. Mp: >280° C. 1H NMR (DMSO-d6; 400 MHz): δ 1.71 (br s, 6), 2.58 (s, 3), 4.02 (s, 4), 6.77 (s, 1), 7.35 (t, 2, J=8.3), 7.67 (dquintet, 1, J=1.4, 6.8), 12.41 (s, 1), 14.51 (s, 1). MS m/z: 329 (M+1 for free base). Anal. Calcd for C18H18F2N4.HCl.1.2H2O: C, 55.99; H, 5.58; N, 14.51; Cl, 9.18. Found: C, 55.99; H, 5.61; N, 14.41; Cl, 9.08.

Workup

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

Sources & evidence

ORD record
ord-1d9e653b86b84fd49193ebb6b7599dbd
Source dataset
uspto-grants-2003_06
Patent number
US06583154B1

Reaction notes

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