Piperidine → HCID 178423282, compound

HRID 635711Notes

Reaction equation

HRID 635711 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[C:8]([N:10]1[CH2:14][CH2:13]CC1)=[CH2:9].ClC1C=CC=CC=1C(=O)C.N1CCCC1.[CH3:30][C:31]1[N:36]=C(Cl)C([N+]([O-])=O)=[C:33](Cl)[N:32]=1.C([N:45]([CH2:49][CH3:50])[CH:46]([CH3:48])[CH3:47])(C)C.N1CCCCC1.Cl[Sn]Cl>CN(C=O)C.Cl[Ti](Cl)(Cl)Cl.CCN(CC)CC>[CH3:48][CH:46]1[CH2:47][CH:30]([C:31]2[NH:36][C:13]3=[CH:9][C:8]([C:3]4[CH:4]=[CH:5][CH:6]=[CH:7][C:2]=4[Cl:1])=[N:10][C:14]3=[CH:33][N:32]=2)[CH2:50][CH2:49][NH:45]1

Participants

11

Reactant 7

HCID 8082PiperidineHCID 24479Stannous ChlorideHCID 31268PyrrolidineHCID 72864Ethanone, 1-(2-chlorophenyl)-HCID 81531DiisopropylethylamineHCID 831924,6-Dichloro-2-methyl-5-nitropyrimidineHCID 18511346HCID 18511346, compound

Product 1

HCID 178423282HCID 178423282, compoundYield 25%

Reagents, catalysts & solvents 3

HCID 24193Titanium TetrachlorideCatalystHCID 6228DimethylformamideSolventHCID 8471TriethylamineSolvent

Procedure

Using the method described in Example 30 by employing [1-(2-chlorophenyl]vinyl]pyrrolidine (freshly prepared before use from 2′-chloro acetophenone (Aldrich Chemical Company), pyrrolidine and TiCl4 (1.06 g, 5.12 mmol), 2-methyl-4,6-dichloro-5-nitropyrimidine (Example 76(b)) (1.10 g, 5.12 mmol), N,N-diisopropylethylamine (0.9 mL, 5.12 mmol), piperidine (0.8 mL, 8.2 mmol), NEt3 (0.9 mL) and SnCl2 (15 mL of a 2 M soln in DMF). The residue was purified by flash chromatography on silica gel with 95:5 CHCl3/MeOH as eluant to give 442 mg (25%) of 2-methyl-4-piperidyl-6-(2-chlorophenyl)pyrrolo[3,2-d]pyrimidine as a brown colored solid. This material (450 mg, 1.37 mmol) was dissolved in 5:1 EtOAc/MeOH (35 mL) and heated to boiling. To the hot solution was added 1 M ethereal HCl (1.40 mL, 1.40 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 343 mg (17%) of the title compound as brown colored needles. Mp: 240-241.5° C. 1H NMR (DMSO-d6; 400 MHz): δ 1.71 (br s, 6), 2.59 (s, 3), 4.03 (s, 4), 6.74 (s, 1), 7.55 (dquintet, 2, J=1.3, 7.8), 7.70 (dt, 2, J=0.9, 8.2), 12.34 (s, 1), 14.64 (s, 1). MS m/z: 327 (M+1 for free base). Anal. Calcd for C18H19ClN4.HCl.H2O: C, 56.70; H, 5.82; N, 14.70; Cl, 18.59. Found: C, 56.93; H, 5.91; N, 14.63; Cl, 18.70.

Workup

  1. customThe residue was purified by flash chromatography on silica gel with 95:5 CHCl3/MeOH as eluant

Sources & evidence

ORD record
ord-8e6cb0e8e5b34885a7f7eb5d9b1f24b5
Source dataset
uspto-grants-2001_02
Patent number
US06187777B1

Reaction notes

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