Piperidine → HCID 178423331, compound

HRID 1371206Notes

Reaction equation

[N:1]1([C:6]([CH3:18])=[CH:7][S:8]([C:11]2[CH:16]=[CH:15][C:14]([Cl:17])=[CH:13][CH:12]=2)(=[O:10])=[O:9])[CH2:5][CH2:4]CC1.ClC1C=CC(S(CC(=O)C)(=O)=O)=CC=1.N1CCCC1.[CH3:38][C:39]1[N:44]=C(Cl)C([N+]([O-])=O)=[C:41](Cl)[N:40]=1.C([N:53]([CH2:57][CH3:58])[CH:54]([CH3:56])[CH3:55])(C)C.N1CCCCC1.Cl[Sn]Cl>CN(C=O)C.Cl[Ti](Cl)(Cl)Cl.CCN(CC)CC>[Cl:17][C:14]1[CH:13]=[CH:12][C:11]([S:8]([CH2:7][C:6]2[CH:18]=[C:4]3[NH:44][C:39]([CH:38]4[CH2:58][CH2:57][NH:53][CH:54]([CH3:55])[CH2:56]4)=[N:40][CH:41]=[C:5]3[N:1]=2)(=[O:9])=[O:10])=[CH:16][CH:15]=1

Participants

Conditions

Temperature: 100 °C

Procedure

Using the method described in Example 30 by employing 1-[(2-pyrrolidinylprop-1-enyl)sulfonyl]-4-chlorobenzene (freshly prepared before use from 4-chlorophenylsulfonylacetone (Lancaster Chemical Company), pyrrolidine and TiCl4 (2.03 g, 7.10 mmol), 2-methyl-4,6-dichloro-5-nitropyrimidine (Example 76(b)) (1.47 g, 7.10 mmol), N,N-diisopropylethylamine (1.3 mL, 7.10 mmol), piperidine (1.1 mL, 11.4 mmol), NEt3 (1.6 mL) and SnCl2 (21 mL of a 2 M soln in DMF). In this example the mixture of enamine, 2-methyl-4,6-dichloro-5-nitropyrimidine and N,N-diisopropylethylamine was stirred at 100° C. for 20 h prior to piperidine addition. 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 100% EtOAc as eluant to give 441 g (15%) of 4-chloro-1-[((2-methyl-4-piperidylpyrrolo[4,5-d]pyrimidin-6-yl)methyl)sulfonyl]benzene as a brown colored solid. This compound (0.44 g, 1.08 mmol) was dissolved in 5:1 EtOAc/MeOH (20 mL) and heated to boiling. To the hot solution was added 1 M ethereal HCl (1.10 mL, 1.10 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 296 mg (9%) of the title compound as a white colored solid. Mp: 199-201° C. 1H NMR (DMSO-d6; 400 MHz): δ 1.57 (m, 4), 1.65 (m, 2), 2.47 (s, 3), 3.85 (br s, 4), 5.02 (s, 2), 6.23 (s, 1), 7.65 (AB q, 4, J=6.2, 6.2), 12.20 (s, 1), 14.18 (s, 1). MS m/z: 405 (M+1 for free base). Anal. Calcd for C19H21ClN4O2S.HCl.0.9H2O: C, 49.87; H, 5.24; N, 12.25; Cl, 15.49. Found: C, 49.85; H, 5.17; N, 12.15; Cl, 15.61.

Workup

stirringThe mixture was stirred at 140° C. for an additional 16 h
temperatureto cool to room temperature
customThe residue was purified by flash chromatography on silica gel with 100% EtOAc as eluant

Sources & evidence

ORD record: ord-8b0803d85b0a4cee97c552b21feda5d1
Source dataset: uspto-grants-2003_06
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US06583154B1

Reaction notes

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