Piperidine → HCID 178489869, compound

HRID 1371192Notes

Reaction equation

HRID 1371192 reaction equation
[CH3:1][O:2][C:3]1[CH:8]=[CH:7][CH:6]=[C:5]([C:9]([N:11]2[CH2:15][CH2:14][CH2:13][CH2:12]2)=C)[CH:4]=1.CC(C1C=CC=C(OC)C=1)=O.N1CCCC1.[CH3:32][C:33]1[N:38]=C(Cl)C([N+]([O-])=O)=[C:35](Cl)[N:34]=1.C([N:47]([CH2:51][CH3:52])[CH:48]([CH3:50])[CH3:49])(C)C.N1CCCCC1.Cl[Sn]Cl>CN(C=O)C.Cl[Ti](Cl)(Cl)Cl.CCN(CC)CC>[CH3:50][CH:48]1[CH2:49][CH:32]([C:33]2[NH:38][C:14]3=[C:13]([CH3:12])[C:9]([C:5]4[CH:6]=[CH:7][CH:8]=[C:3]([O:2][CH3:1])[CH:4]=4)=[N:11][C:15]3=[CH:35][N:34]=2)[CH2:52][CH2:51][NH:47]1

Participants

11

Reactant 7

HCID 8082PiperidineHCID 114603-MethoxyacetophenoneHCID 24479Stannous Chloride2×HCID 31268PyrrolidineHCID 81531DiisopropylethylamineHCID 831924,6-Dichloro-2-methyl-5-nitropyrimidineHCID 18511388HCID 18511388, compound

Product 1

HCID 178489869HCID 178489869, compoundYield 34%

Reagents, catalysts & solvents 3

HCID 24193Titanium TetrachlorideCatalystHCID 6228DimethylformamideSolventHCID 8471TriethylamineSolvent

Conditions

Temperature
140 °C

Procedure

Using the method described in Example 30 by employing 1-methoxy-3-(1-pyrrolidinylvinyl)benzene (freshly prepared before use from 3-methoxyacetophenone (Aldrich Chemical Company), pyrrolidine and TiCl4 (2.49 g, 12.3 mmol), 2-methyl-4,6-dichloro-5-nitropyrimidine (Example 76(b)) (2.52 g, 12.3 mmol), N,N-diisopropylethylamine (2.1 mL, 12.3 mmol), piperidine (1.9 mL, 19.7 mmol), NEt3 (2.0 mL) and SnCl2 (37 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 95:5 CHCl3/MeOH as eluant to give 1.35 g (34%) of 1-[2,7-dimethyl-4-piperidylpyrrolo[4,5-d]pyrimidin-6-yl]-3-methoxybenzene as a beige colored solid. This compound (463 mg, 1.43 mmol) was dissolved in 5:1 EtOAc/MeOH (40 mL) and heated to boiling. To the hot solution was added 1 M ethereal HCl (1.50 mL, 1.50 mmol). The solution was allowed 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 485 mg (32%) of the title compound as a white colored solid. Mp: 241-243° C. 1H NMR (DMSO-d6; 400 MHz): δ 1.64 (br s, 6), 2.50 (s, 3), 3.79 (s, 3), 3.98 (br s, 4), 6.84 (s, 1), 7.03 (dd, 1, J=1.0, 8.3), 7.38 (t, 1, J=3.9), 7.44-7.46 (m, 2), 11.91 (s, 1), 14.36 (s, 1). MS m/z: 323 (M+1 for free base). Anal. Calcd for C19H22N4O.HCl.0.5H2O: C, 62.03; H, 6.58; N, 15.23; Cl, 9.64. Found: C, 62.08; H, 6.56; N, 15.17; Cl, 9.75.

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 95:5 CHCl3/MeOH as eluant

Sources & evidence

ORD record
ord-7249edd9221a4936834fce2e4cbf9b25
Source dataset
uspto-grants-2003_06
Patent number
US06583154B1

Reaction notes

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