Piperidine → HCID 178423305, compound

HRID 1371209Notes

Reaction equation

HRID 1371209 reaction equation
[CH:1]1[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[CH:4]=[CH:3]C=1C(N1CCCC1)=C.[NH:18]1[CH2:22][CH2:21][CH2:20][CH2:19]1.[CH3:23][C:24]1[N:29]=C(Cl)C([N+]([O-])=O)=[C:26](Cl)[N:25]=1.[CH:35]([N:38](CC)[CH:39]([CH3:41])[CH3:40])([CH3:37])[CH3:36].N1CCCCC1.Cl[Sn]Cl>CN(C=O)C.Cl[Ti](Cl)(Cl)Cl.CCN(CC)CC>[CH3:41][CH:39]1[CH2:40][CH:23]([C:24]2[NH:29][C:21]3=[CH:20][CH:19]=[N:18][C:22]3=[CH:26][N:25]=2)[CH2:37][CH:35]([C:36]2[CH:3]=[CH:4][C:5]3[C:10](=[CH:9][CH:8]=[CH:7][CH:6]=3)[CH:1]=2)[NH:38]1

Participants

10

Reactant 6

HCID 8082PiperidineHCID 24479Stannous Chloride2×HCID 31268PyrrolidineHCID 81531DiisopropylethylamineHCID 831924,6-Dichloro-2-methyl-5-nitropyrimidineHCID 153464331-[1-(Naphthalen-2-yl)ethenyl]pyrrolidine

Product 1

HCID 178423305HCID 178423305, compoundYield 55%

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-naphthyl)vinyl]pyrrolidine (freshly prepared before use from 2′-acetylnaphthone (Aldrich Chemical Company), pyrrolidine and TiCl4 (1.91 g, 8.60 mmol), 2-methyl-4,6-dichloro-5-nitropyrimidine (Example 76(b)) (1.78 g, 8.60 mmol), N,N-diisopropylethylamine (1.5 mL, 8.6 mmol), piperidine (1.4 mL, 13.8 mmol), NEt3 (1.9 mL) and SnCl2 (23 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 2.5 h then the heating was discontinued and the mixture was allowed to cool to room temperature. The mixture was stirred at room temperature an additional 36 h. The residue was purified by flash chromatography on silica gel with 95:5 CHCl3/MeOH as eluant to give 1.25 g (55%) of 2-methyl-6-(2-naphthyl)-4-piperidylpyrrolo[3,2-d]pyrimidine as a beige colored solid. This compound (1.25 g, 3.64 mmol) was dissolved in 5:1 EtOAc/MeOH (60 mL) and heated to boiling. To the hot solution was added 1 M ethereal HCl (3.60 mL, 3.60 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 1.02 g (40%) of the title compound as a yellow colored powder. Mp: >280° C. 1H NMR (DMSO-d6; 400 MHz): δ 1.67 (br s, 6), 2.52 (s, 3), 4.04 (t, 4, J=4.9), 6.98 (s, 1), 7.55 (m, 2), 7.94 (t, 1, J=4.0), 8.00 (d, 1, J=5.4), 8.02 (br s, 2), 8.50 (s, 1), 12.09 (s, 1), 14.27 (s, 1). MS m/z: 343 (M+1 for free base). Anal. Calcd for C22H22N4.HCl.1.5H2O: C, 65.09; H, 6.46; N, 13.81; Cl, 8.73. Found: C,65.00; H, 66.45; N, 13.80; Cl, 8.76.

Workup

  1. customwas added to the reaction mixture at 140° C
  2. temperatureto cool to room temperature
  3. stirringThe mixture was stirred at room temperature an additional 36 h
  4. customThe residue was purified by flash chromatography on silica gel with 95:5 CHCl3/MeOH as eluant

Sources & evidence

ORD record
ord-68ee2c715c5c48fcbc8b2449bc663973
Source dataset
uspto-grants-2003_06
Patent number
US06583154B1

Reaction notes

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