Piperidine → HCID 178488896, compound

HRID 1371189Notes

Reaction equation

HRID 1371189 reaction equation
[N:1]1([C:6]([C:9]2[CH:14]=[CH:13][C:12]([O:15][CH3:16])=[CH:11][CH:10]=2)=[CH:7][CH3:8])[CH2:5][CH2:4]CC1.COC1C=CC(C(=O)CC)=CC=1.N1CCCC1.[CH3:34][C:35]1[N:40]=C(Cl)C([N+]([O-])=O)=[C:37](Cl)[N:36]=1.C([N:49]([CH2:53][CH3:54])[CH:50]([CH3:52])[CH3:51])(C)C.N1CCCCC1.Cl[Sn]Cl>CN(C=O)C.Cl[Ti](Cl)(Cl)Cl.CCN(CC)CC>[CH3:52][CH:50]1[CH2:51][CH:34]([C:35]2[NH:40][C:4]3=[C:7]([CH3:8])[C:6]([C:9]4[CH:10]=[CH:11][C:12]([O:15][CH3:16])=[CH:13][CH:14]=4)=[N:1][C:5]3=[CH:37][N:36]=2)[CH2:54][CH2:53][NH:49]1

Participants

11

Reactant 7

HCID 8082PiperidineHCID 24479Stannous Chloride2×HCID 31268PyrrolidineHCID 671444-PropanoylanisoleHCID 81531DiisopropylethylamineHCID 831924,6-Dichloro-2-methyl-5-nitropyrimidineHCID 57071860HCID 57071860, compound

Product 1

HCID 178488896HCID 178488896, compoundYield 33%

Reagents, catalysts & solvents 3

HCID 24193Titanium TetrachlorideCatalystHCID 6228DimethylformamideSolventHCID 8471TriethylamineSolvent

Conditions

Temperature
140 °C

Procedure

Using the method described in Example 30 by employing 4-(1-pyrrolidinylprop-1-enyl)-1-methoxy benzene (freshly prepared before use from 4′-methoxy propiophenone (Aldrich Chemical Company), pyrrolidine and TiCl4 (1.77 g, 8.16 mmol), 2-methyl-4,6-dichloro-5-nitropyrimidine (Example 76(b)) (1.70 g, 8.20 mmol), N,N-diisopropylethylamine (1.4 mL, 8.20 mmol), piperidine (1.3 mL, 13.1 mmol), NEt3 (1.4 mL) and SnCl2 (25 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 894 mg (33%) of 1-[2,7-dimethyl-4-piperidylpyrrolo[4,5-d]pyrimidin-6-yl]-4-methoxybenzene as a brown colored foam. This compound (440 mg, 1.31 mmol) was dissolved in 5:1 EtOAc/MeOH (20 mL) and heated to boiling. To the hot solution was added 1 M ethereal HCl (1.30 mL, 1.30 mmol). The solution was allowed to cool to room temperature. The resulting crystals were collected by filtration, washed with EtOAc (2×10 mL), Et2O (3×15mL) and dried under vacuum at 60° C. to give 202 mg (14%) of the title compound as a beige colored sandy solid. Mp: >280° C. 1H HMR (DMSO-d6; 400 MHz): δ 1.62 (br s, 6), 2.24 (s, 3), 2.55 (s, 3), 3.94 (br s, 4), 7.08 (d, 2, J=8.7), 7.55 (d, 2, J=8.7), 11.76 (s, 1), 13.77 (s, 1). MS m/z: 337 (M+1 for free base). Anal. Calcd for C20H24N4O.HCl: C, 64.42/; H, 6.76; N, 15.03; Cl, 9.51. Found: C, 64.40; H, 6.68; N, 15.03; Cl, 9.60.

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-f1b1be536b0344d4918c8f578ea517e7
Source dataset
uspto-grants-2003_06
Patent number
US06583154B1

Reaction notes

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