Piperidine → HCID 178430017, compound

HRID 1371188Notes

Reaction equation

HRID 1371188 reaction equation
ClC1C=[C:4]([C:9]([N:12]2CCCC2)=[CH:10]C)C=CC=1Cl.[Cl:17][C:18]1[CH:19]=[C:20]([C:25](=O)[CH2:26][CH3:27])[CH:21]=[CH:22][C:23]=1[Cl:24].N1C[CH2:32][CH2:31][CH2:30]1.C[C:35]1[N:40]=[C:39](Cl)[C:38]([N+:42]([O-])=O)=[C:37](Cl)[N:36]=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>[Cl:17][C:18]1[CH:19]=[C:20]([CH:25]2[NH:12][CH:9]([CH3:10])[CH2:4][CH:27]([C:35]3[NH:40][C:39]4=[C:31]([CH3:32])[CH:30]=[N:42][C:38]4=[CH:37][N:36]=3)[CH2:26]2)[CH:21]=[CH:22][C:23]=1[Cl:24]

Participants

11

Reactant 7

HCID 8082PiperidineHCID 24479Stannous Chloride2×HCID 31268PyrrolidineHCID 81531DiisopropylethylamineHCID 831924,6-Dichloro-2-methyl-5-nitropyrimidineHCID 5995981-(3,4-Dichlorophenyl)-1-propanoneHCID 86756421HCID 86756421, compound

Product 1

HCID 178430017HCID 178430017, compoundYield 21%

Reagents, catalysts & solvents 3

HCID 24193Titanium TetrachlorideCatalystHCID 6228DimethylformamideSolventHCID 8471TriethylamineSolvent

Conditions

Temperature
140 °C

Procedure

Using the method described in Example 30 by employing [(1-(3,4-dichlorophenyl)prop-1-enyl]pyrrolidine (freshly prepared before use from 3′,4′-dichloropropiophenone (Aldrich Chemical Company), pyrrolidine and TiCl4 (1.64 g, 6.40 mmol), 2-methyl-4,6-dichloro-5-nitropyrimidine (Example 76(b)) (1.30 g, 6.40 mmol), N,N-diisopropylethylamine (1.1 mL, 6.40 mmol), piperidine (1.0 mL, 10.2 mmol), NEt3 (1.1 mL) and SnCl2 (19 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 511 mg (21%) of 6-(3,4-dichlorophenyl)-2,7-dimethyl-4-piperidylpyrrolo[3,2-d]pyrimidine as a brown colored oil. This compound (511 mg, 1.38 mmol) was dissolved in 5:1 EtOAc/MeOH (30 mL) and heated to boiling. To the hot solution was added 1 M ethereal HCl (1.40 mL, 1.40 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 90 mg (3%) of the title compound as beige colored needles. Mp: >280° C. 1H HMR (DMSO-d6; 400 MHz): δ 1.64 (br s, 6), 2.27 (s, 3), 2.56 (s, 3), 3.98 (br t, 4, J=5.4), 7.60 (dd, 1, J=2.0, 8.4), 7.78 (d, 1, J=8.4), 7.91 (d, 1, J=2.0), 11.93 (s, 1), 13.97 (s, 1). MS m/z: 375 (M+1 for free base). Anal. Calcd for C19H20Cl2N4HCl.0.5H2O: C, 54.23; H, 5.27; N, 13.32; Cl, 25.28. Found: C, 54.35; H, 5.23; N, 13.29; Cl, 25.54.

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-7811952b2aaa46cfa3024e8851ba0297
Source dataset
uspto-grants-2003_06
Patent number
US06583154B1

Reaction notes

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