Piperidine → HCID 178423303, compound

HRID 1371181Notes

Reaction equation

HRID 1371181 reaction equation
C1[C:13]2[CH2:12][C:11]3[C:6](=[CH:7][CH:8]=[CH:9]C=3)[C:5]=2C=CC=1C(N1CCCC1)=C.C([C:24]1[CH:36]=[CH:35][C:34]2C3C(=CC=CC=3)CC=2C=1)(=O)C.[NH:37]1[CH2:41][CH2:40][CH2:39][CH2:38]1.[CH3:42][C:43]1[N:48]=C(Cl)C([N+]([O-])=O)=[C:45](Cl)[N:44]=1.C([N:57]([CH2:61][CH3:62])[CH:58]([CH3:60])[CH3:59])(C)C.N1CCCC[CH2:64]1.Cl[Sn]Cl>CN(C=O)C.Cl[Ti](Cl)(Cl)Cl.CCN(CC)CC>[CH:7]1[C:6]2[CH2:5][C:13]3[C:12](=[CH:24][CH:36]=[CH:35][CH:34]=3)[C:11]=2[CH:64]=[CH:9][C:8]=1[CH:61]1[NH:57][CH:58]([CH3:59])[CH2:60][CH:42]([C:43]2[NH:48][C:40]3=[CH:39][CH:38]=[N:37][C:41]3=[CH:45][N:44]=2)[CH2:62]1

Participants

11

Reactant 7

HCID 8082PiperidineHCID 24479Stannous Chloride2×HCID 31268PyrrolidineHCID 699082-AcetylfluoreneHCID 81531DiisopropylethylamineHCID 831924,6-Dichloro-2-methyl-5-nitropyrimidineHCID 18511320HCID 18511320, compound

Product 1

HCID 178423303HCID 178423303, compoundYield 18%

Reagents, catalysts & solvents 3

HCID 24193Titanium TetrachlorideCatalystHCID 6228DimethylformamideSolventHCID 8471TriethylamineSolvent

Procedure

Using the method described in Example 30 by employing (1-fluoren-2-ylvinyl)pyrrolidine (freshly prepared before use from 2-acetylfluorene (Aldrich Chemical Company), pyrrolidine and TiCl4 (1.27 g, 4.86 mmol), 2-methyl-4,6-dichloro-5-nitropyrimidine (Example 76(b)) (1.01 g, 4.86 mmol), N,N-diisopropylethylamine (0.9 mL, 4.86 mmol), piperidine (0.8 mL, 7.8 mmol), NEt3 (1.0 mL) and SnCl2 (15 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 purified by flash chromatography on silica gel with 95:5 CHCl3/MeOH as eluant to give 325 mg (18%) of 6-fluoren-2-yl-2-methyl-4-piperidylpyrrolo[3,2-d]pyrimidine as a beige colored solid. This material (321 mg, 0.86 mmol) was dissolved in 1:10 EtOAc/MeOH (60 mL) and heated to boiling. To the hot solution was added 1 M ethereal HCl (0.90 mL, 0.90 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 138 mg (7%) of the title compound as a beige colored solid. Mp: >280° C. 1H HMR (DMSO-d6; 400 MHz): δ 1.73 (br s, 6), 2.57 (s, 3), 4.05 (s, 2), 4.08 (br s, 4), 6.97 (s, 1), 7.39 (t, 1, J=7.2), 7.44 (t, 1, J=7.0), 7.66 (d, 1, J=7.2), 8.02 (d, 2, J=7.7), 8.10 (d, 1, J=8.0), 8.21 (s, 1), 12.01 (s, 1), 14.27 (s, 1). MS m/z: 381 (M+1 for free base). Anal. Calcd for C25H24N4.HCl.1.5H2O: C, 67.58; H, 6.31; N, 12.61; Cl, 7.88. Found: C, 67.77; H, 6.25; N, 12.54; Cl, 8.06.

Workup

  1. customwas stirred at room temperature for 48 h
  2. customThe residue was purified by flash chromatography on silica gel with 95:5 CHCl3/MeOH as eluant

Sources & evidence

ORD record
ord-7e5435c3aa6546ae8e0af0ff2aeda71e
Source dataset
uspto-grants-2003_06
Patent number
US06583154B1

Reaction notes

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