2-Methylpiperidine → HCID 178433067, compound

HRID 1371200Notes

Reaction equation

HRID 1371200 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]([N:10]2[CH2:14][CH2:13][CH2:12]C2)=C)=[CH:4][CH:3]=1.FC1C=CC(C(=O)C)=CC=1.N1CCCC1.[CH3:30][C:31]1[N:36]=C(Cl)C([N+]([O-])=O)=[C:33](Cl)[N:32]=1.C(N(CC)C(C)C)(C)C.[CH3:51][CH:52]1[CH2:57][CH2:56][CH2:55][CH2:54][NH:53]1.Cl[Sn]Cl>CN(C=O)C.Cl[Ti](Cl)(Cl)Cl.CCN(CC)CC>[F:1][C:2]1[CH:3]=[CH:4][C:5]([C:8]2[CH:12]=[C:13]3[C:14]([N:10]=2)=[C:33]([N:53]2[CH2:54][CH2:55][CH2:56][CH2:57][CH:52]2[CH3:51])[N:32]=[C:31]([CH3:30])[NH:36]3)=[CH:6][CH:7]=1

Participants

11

Reactant 7

HCID 79742-MethylpiperidineHCID 98284'-FluoroacetophenoneHCID 24479Stannous Chloride2×HCID 31268PyrrolidineHCID 81531DiisopropylethylamineHCID 831924,6-Dichloro-2-methyl-5-nitropyrimidineHCID 22719899HCID 22719899, compound

Product 1

HCID 178433067HCID 178433067, compoundYield 24%

Reagents, catalysts & solvents 3

HCID 24193Titanium TetrachlorideCatalystHCID 6228DimethylformamideSolventHCID 8471TriethylamineSolvent

Conditions

Temperature
140 °C

Procedure

Using the method described in Example 30 by employing [1-(4-fluorophenyl)vinyl]pyrrolidine (freshly prepared before use from 4′-fluoroacetophenone (Aldrich Chemical Company), pyrrolidine and TiCl4 (2.17 g, 11.4 mmol), 2-methyl-4,6-dichloro-5-nitropyrimidine (Example 76(b)) (2.42 g, 11.4 mmol), N,N-diisopropylethylamine (2.0 mL, 11.4 mmol), 2-methylpiperidine (2.1 mL, 18.2 mmol), NEt3 (2.0 mL) and SnCl2 (34 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 0.88 g (24%) of 6-(4-fluorophenyl)-2-methyl-4-(2-methylpiperidyl)pyrrolo[3,2-d]pyrimidine as a beige colored solid. This compound (882 mg, 2.71 mmol) was dissolved in 10:1 EtOAc/MeOH (50 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 573 mg (14%) of the title compound as a white colored solid. Mp: 274-276° C. 1H NMR (DMSO-d6; 400 MHz): δ 1.20 (d, 3, J=6.9), 1.40-1.73 (m, 6), 2.44 (s, 3), 3.35 (br s, 1), 4.48 (br s, 1), 5.13 (br s, 1), 6.75 (s, 1), 7.28 (t, 2, J=8.9), 7.89 (dd, 2, J=5.4,5.4), 11.79 (s, 1), 14.04 (s, 1). MS m/z: 325 (M+1 for free base). Anal. Calcd for C19H21FN4.HCl.H2O: C, 60.23; H, 6.39; N, 14.79; Cl, 9.36.. Found: C, 60.60; H, 6.28; N, 14.90; Cl, 9.35.

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-9872a1a4551e436cb181c91a4a3afbd2
Source dataset
uspto-grants-2003_06
Patent number
US06583154B1

Reaction notes

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