Piperidine → HCID 178423683, compound

HRID 635721Notes

Reaction equation

HRID 635721 reaction equation
N1[CH2:5][CH2:4][CH2:3][CH2:2]1.[CH3:6][C:7]1[N:12]=[C:11](Cl)C([N+]([O-])=O)=C(Cl)[N:8]=1.[CH:18]([N:21](CC)[CH:22]([CH3:24])[CH3:23])([CH3:20])[CH3:19].N1CC[CH2:30][CH2:29][CH2:28]1.Cl[Sn]Cl.CC[N:38]([CH2:41][CH3:42])[CH2:39][CH3:40]>CN(C=O)C.Cl[Ti](Cl)(Cl)Cl.C(Cl)(Cl)Cl.CO>[CH3:30][C:29]1[CH:28]=[C:24]([CH:22]2[NH:21][CH:18]([CH3:19])[CH2:20][CH:6]([C:7]3[NH:8][C:40]4=[CH:42][CH:41]=[N:38][C:39]4=[CH:11][N:12]=3)[CH2:23]2)[CH:5]=[CH:4][C:3]=1[CH3:2]

Participants

10

Reactant 6

HCID 8082PiperidineHCID 8471TriethylamineHCID 24479Stannous Chloride2×HCID 31268PyrrolidineHCID 81531DiisopropylethylamineHCID 831924,6-Dichloro-2-methyl-5-nitropyrimidine

Product 1

HCID 178423683HCID 178423683, compoundYield 31%

Reagents, catalysts & solvents 3

HCID 24193Titanium TetrachlorideCatalystHCID 6228DimethylformamideSolventHCID 21584188Chloroform methanolSolvent

Procedure

Using the method described in Example 30 by employing[1-(3,4-dimethylphenyl)vinyl]pyrrolidine (freshly prepared before use from 3,4-dimethyl acetophenone (Aldrich Chemical Company), pyrrolidine and TiCl4 (1.22 g, 6.07 mmol), 2-methyl-4,6-dichloro-5-nitropyrimidine (Example 76(b)) (1.30 g, 6.07 mmol), N,N-diisopropylethylamine (1.1 mL, 6.07 mmol), piperidine (1.0 mL, 9.7 mmol), NEt3 (1.1 mL) and SnCl2 (18 mL of a 2 M soln in DMF). In this example the reaction mixture was stirred at room temperature for 48 h after the addition of 2 M SnCl2. The residue was mpurified by flash chromatography on silica gel with 95:5 CHCl3/MeOH as eluant to give 605 mg (31%) of 6-(3,4-dimethylphenyl)-2-methyl-4-piperidylpyrrolo[3,2-d]pyrimidine as a beige colored solid. This material (605 mg, 1.88 mmol) was dissolved in 5:1 EtOAc/MeOH (35 mL) and heated to boiling. To the hot solution was added 1 M ethereal HCl (1.90 mL, 1.90 mmol). The solution was left 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 518 mg (24%) of the title compound as a beige colored powder. Mp: 198-201° C. 1H NMR (DMSO-D6; 400 MHz): δ 1.70 (br s, 6), 2.30 (s, 3), 2.33 (s, 3), 2.56 (s, 3), 4.05 (s, 4), 6.84 (s, 1), 7.32 (d, 1, J=7.9), 7.70 (d, 1, J=7.8), 7.74 (s, 1), 11.91 (s, 1), 14.38 (s, 1). MS m/z: 321 (M+1 for free base). Anal. Calcd for C20H24N4.HCl.0.75H2O: C, 64.95; H, 7.17; N, 15.15; Cl, 9.47. Found: C, 65.13; H, 7.11; N, 14.98; Cl, 9.54.

Workup

  1. customwas stirred at room temperature for 48 h

Sources & evidence

ORD record
ord-333f163276714c30873dcbe1e1723af4
Source dataset
uspto-grants-2001_02
Patent number
US06187777B1

Reaction notes

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