Piperidine → HCID 178489270, compound

HRID 1371199Notes

Reaction equation

HRID 1371199 reaction equation
[CH3:1][O:2][C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][C:4]=1[C:9](=O)[CH3:10].N1CCCC1.[CH3:17][C:18]1[N:23]=[C:22](Cl)[C:21]([N+:25]([O-])=O)=[C:20](Cl)[N:19]=1.[CH:29]([N:32](CC)[CH:33](C)[CH3:34])([CH3:31])[CH3:30].N1CCCCC1.Cl[Sn]Cl>CN(C=O)C.Cl[Ti](Cl)(Cl)Cl.CCN(CC)CC>[CH3:1][O:2][C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][C:4]=1[C:9]1[CH:10]=[C:20]2[NH:19][C:18]([CH:17]3[CH2:34][CH2:33][NH:32][CH:29]([CH3:31])[CH2:30]3)=[N:23][CH:22]=[C:21]2[N:25]=1

Participants

10

Reactant 6

HCID 8082PiperidineHCID 24479Stannous Chloride2×HCID 31268PyrrolidineHCID 684812'-MethoxyacetophenoneHCID 81531DiisopropylethylamineHCID 831924,6-Dichloro-2-methyl-5-nitropyrimidine

Product 1

HCID 178489270HCID 178489270, compoundYield 74%

Reagents, catalysts & solvents 3

HCID 24193Titanium TetrachlorideCatalystHCID 6228DimethylformamideSolventHCID 8471TriethylamineSolvent

Conditions

Temperature
140 °C

Procedure

Using the method described in Example 30 by employing 2-methoxy-1-(1-pyrrolidinylvinyl)furan (freshly prepared before use from 2′-methoxy acetophenone (Aldrich Chemical Company), pyrrolidine and TiCl4 (2.14 g, 10.5 mmol), 2-methyl-4,6-dichloro-5-nitropyrimidine (Example 76(b)) (2.25 g, 10.5 mmol), N,N-diisopropylethylamine (1.8 mL, 10.5 mmol), piperidine (1.7 mL, 16.8 mmol), NEt3 (1.8 mL) and SnCl2 (32 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 2.49 g (74%) of 2-methoxy-1-[2-methyl-4-piperidylpyrrolo[4,5-d]pyrimidin-6-yl]benzene as a beige colored foam. This compound (864 mg, 2.67 mmol) was dissolved in 10:1 EtOAc/MeOH (60 mL) and heated to boiling. To the hot solution was added 1 M ethereal HCl (2.70 mL, 2.70 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 654 mg (50%) of the title compound as a pale yellow colored solid. Mp: 261-263° C. 1H HMR (DMSO-d6; 400 MHz): δ 1.64 (br s, 6), 2.51 (s, 3), 3.83 (s, 3), 3.97 (br s, 4), 6.72 (s, 1), 7.07 (dt, 1, J=0.7, 7.4), 7.18 (d, 1, J=8.2), 7.44 (dt, 1, J=1.7, 7.1), 7.67 (dd, 1, J=1.3, 7.6), 11.74 (s, 1), 14.31 (s, 1). MS m/z: 411 (M+1 for free base). Anal. Calcd for C19H22N4O.HCl.H2O: C, 60.55; H, 6.69; N, 14.87; Cl, 9.41. Found: C, 60.68; H, 6.78; N, 14.82; Cl, 9.52.

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-81b16698561f4487b90b6c96dfb4a0b0
Source dataset
uspto-grants-2003_06
Patent number
US06583154B1

Reaction notes

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