Piperidine → HCID 178423277, compound

HRID 1371210Notes

Reaction equation

HRID 1371210 reaction equation
[N:1]1([C:6]([C:8]2[S:12][C:11]3[CH:13]=[CH:14][CH:15]=[CH:16][C:10]=3[CH:9]=2)=[CH2:7])[CH2:5][CH2:4]CC1.C(C1SC2C=CC=CC=2C=1)(=O)C.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>[CH3:52][CH:50]1[CH2:51][CH:34]([C:35]2[NH:40][C:4]3=[CH:7][C:6]([C:8]4[S:12][C:11]5[CH:13]=[CH:14][CH:15]=[CH:16][C:10]=5[CH:9]=4)=[N:1][C:5]3=[CH:37][N:36]=2)[CH2:54][CH2:53][NH:49]1

Participants

11

Reactant 7

HCID 8082PiperidineHCID 24479Stannous Chloride2×HCID 31268PyrrolidineHCID 81531DiisopropylethylamineHCID 831924,6-Dichloro-2-methyl-5-nitropyrimidineHCID 898052-Acetylbenzo[b]thiopheneHCID 18511178HCID 18511178, compound

Product 1

HCID 178423277HCID 178423277, compoundYield 40%

Reagents, catalysts & solvents 3

HCID 24193Titanium TetrachlorideCatalystHCID 6228DimethylformamideSolventHCID 8471TriethylamineSolvent

Conditions

Temperature
140 °C

Procedure

Using the method described in Example 30 by employing 2-(1-pyrrolidinylvinyl)benzo[b]thiophene (freshly prepared before use from 2-acetylbenzo[b]thiophene (Avocado Chemical Company), pyrrolidine and TiCl4 (1.71 g, 7.45 mmol), 2-methyl-4,6-dichloro-5-nitropyrimidine (Example 76(b)) (1.54 g, 7.45 mmol), N,N-diisopropylethylamine (1.3 mL, 7.45 mmol), piperidine (1.2 mL, 11.9 mmol), NEt3 (1.7 mL) and SnCl2 (22 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 1.04 g (40%) of 2-[2-methyl-4-piperidylpyrrolo[4,5-d]pyrimidin-6-yl]benzo[b]thiophene as a yellow colored powder. This compound (1.04 g, 2.98 mmol) was dissolved in 5:1 EtOAc/MeOH (50 mL) and heated to boiling. To the hot solution was added 1 M ethereal HCl (3.00 mL, 3.00 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 0.88 g (31%) of the title compound as a yellow colored powder. Mp: >280° C. 1H NMR (DMSO-d6; 400 MHz): δ 1.66 (br s, 6), 2.51 (s, 3), 4.00 (br s, 4), 6.74 (s, 1), 7.39 (m, 2), 7.91 (t, 1, J=6.9), 8.00 (t, 1, J=4.0), 8.16 (s, 1), 12.22 (s, 1), 14.21 (s, 1). MS m/z: 349 (M+1 for free base). Anal. Calcd for C20H20N4S.HCl.0.70H2O: C, 60.42; H, 5.68; N, 14.10; Cl, 8.92. Found: C, 60.38; H, 5.56; N, 13.93; Cl, 9.03.

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-2d87083e3a7249c0aaf7ef8215730ec9
Source dataset
uspto-grants-2003_06
Patent number
US06583154B1

Reaction notes

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