Piperidine → HCID 178488443, compound

HRID 1371174Notes

Reaction equation

HRID 1371174 reaction equation
[F:1][C:2]1[CH:7]=[C:6]([C:8]([N:10]2[CH2:14][CH2:13][CH2:12]C2)=C)[CH:5]=[CH:4][C:3]=1[O:15][CH3:16].CC(C1C=CC(OC)=C(F)C=1)=O.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>[F:1][C:2]1[CH:7]=[C:6]([C:8]2[CH:12]=[C:13]3[NH:40][C:35]([CH:34]4[CH2:54][CH2:53][NH:49][CH:50]([CH3:51])[CH2:52]4)=[N:36][CH:37]=[C:14]3[N:10]=2)[CH:5]=[CH:4][C:3]=1[O:15][CH3:16]

Participants

11

Reactant 7

HCID 8082PiperidineHCID 24479Stannous Chloride2×HCID 31268PyrrolidineHCID 81531DiisopropylethylamineHCID 831924,6-Dichloro-2-methyl-5-nitropyrimidineHCID 968281-(3-Fluoro-4-methoxyphenyl)ethan-1-oneHCID 18511300HCID 18511300, compound

Product 1

HCID 178488443HCID 178488443, compoundYield 23%

Reagents, catalysts & solvents 3

HCID 24193Titanium TetrachlorideCatalystHCID 6228DimethylformamideSolventHCID 8471TriethylamineSolvent

Procedure

Using the method described in Example 30 by employing 2-fluoro-1-methoxy-4-(1-pyrrolidinylvinyl)benzene (freshly prepared before use from 3-fluoro-4-methoxyacetophenone (Aldrich Chemical Company), pyrrolidine and TiCl4 (1.37 g, 6.19 mmol), 2-methyl-4,6-dichloro-5-nitropyrimidine (Example 76(b)) (1.30 g, 6.19 mmol), N,N-diisopropylethylamine (1.1 mL, 6.19 mmol), piperidine (1.0 mL, 9.9 mmol), NEt3 (1.1 mL) and SnCl2 (19 mL of a 2 M soln in DMF). In this example the 2 M SnCl2 solution was added to the reaction mixture at 140° C. Heating was then discontinued and the mixture was allowed to cool to room temperature. The mixture was stirred at room temperature for an additional 48 h. The residue was purified by flash chromatography on silica gel with 95:5 CHCl3/MeOH as eluant to give 481 mg (23%) of 2-fluoro-1-methoxy-4-[2-methyl-4-piperidylpyrrolo[4,5-d]pyrimidin-6-yl]benzene as a beige colored solid. This compound (481 mg, 1.41 mmol) was dissolved in 4:1 EtOAc/MeOH (30 mL) and heated to boiling. To the hot solution was added 1 M ethereal HCl (1.40 mL, 1.40 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 372 mg (16%) of the title compound as a beige colored solid. Mp: 262-264° C. 1H NMR (DMSO-d6; 500 MHz): δ 1.69 (br s, 6), 2.56 (s, 3), 3.92 (s, 3), 4.05 (br t, 4, J=5.4), 6.59 (s, 1), 7.33 (t, 1, J=8.8), 7.80 (d, 1, J=8.6), 7.96 (dd, 1, J=2.0, 12.7), 11.82 (s, 1), 14.20 (s, 1). MS m/z: 341 (M+1 for free base). Anal. Calcd for C19H21FN4O.HCl.0.5H2O: C, 59.08; H, 5.96; N, 14.51; Cl, 9.08. Found: C, 58.90; H, 5.89; N, 14.46; Cl, 9.30.

Workup

  1. customwas added to the reaction mixture at 140° C
  2. temperatureHeating
  3. customThe residue was purified by flash chromatography on silica gel with 95:5 CHCl3/MeOH as eluant

Sources & evidence

ORD record
ord-42412a2262e043008607d5c5d015880a
Source dataset
uspto-grants-2003_06
Patent number
US06583154B1

Reaction notes

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