Piperidine → HCID 178423294, compound

HRID 635736Notes

Reaction equation

HRID 635736 reaction equation
[CH3:1][S:2]([C:5]1[CH:10]=[CH:9][C:8]([C:11]([N:13]2[CH2:17][CH2:16][CH2:15]C2)=C)=[CH:7][CH:6]=1)(=[O:4])=[O:3].N1CCCC1.[CH3:23][C:24]1[N:29]=C(Cl)C([N+]([O-])=O)=[C:26](Cl)[N:25]=1.C([N:38]([CH2:42][CH3:43])[CH:39]([CH3:41])[CH3:40])(C)C.N1CCCCC1.Cl[Sn]Cl>CN(C=O)C.Cl[Ti](Cl)(Cl)Cl.CCN(CC)CC>[CH3:41][CH:39]1[CH2:40][CH:23]([C:24]2[NH:29][C:16]3=[CH:15][C:11]([C:8]4[CH:7]=[CH:6][C:5]([S:2]([CH3:1])(=[O:3])=[O:4])=[CH:10][CH:9]=4)=[N:13][C:17]3=[CH:26][N:25]=2)[CH2:43][CH2:42][NH:38]1

Participants

10

Reactant 6

HCID 8082PiperidineHCID 24479Stannous Chloride2×HCID 31268PyrrolidineHCID 81531DiisopropylethylamineHCID 831924,6-Dichloro-2-methyl-5-nitropyrimidineHCID 54379438HCID 54379438, compound

Product 1

HCID 178423294HCID 178423294, compoundYield 37%

Reagents, catalysts & solvents 3

HCID 24193Titanium TetrachlorideCatalystHCID 6228DimethylformamideSolventHCID 8471TriethylamineSolvent

Conditions

Temperature
140 °C

Procedure

Using the method described in Example 30 by employing 1-(methylsulfonyl)-4-(1-pyrrolidinylvinyl) benzene (freshly prepared before use from 3-methyl sulfonylacetophenone (Acros Chemical Company), pyrrolidine and TiCl4 (2.01 g, 8.00 mmol), 2-methyl-4,6-dichloro-5-nitropyrimidine (Example 76(b)) (1.71 g, 8.00 mmol), N,N-diisopropylethylamine (1.4 mL, 8.0 mmol), piperidine (1.3 mL, 12.8 mmol), NEt3 (1.4 mL) and SnCl2 (24 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 1.10 g (37%) of 1-[2-methyl-4-piperidyl pyrrolo[4,5-d]pyrimidin-6-yl]-4-(methylsulfonyl)benzene as a beige colored solid. This compound (1.10 g, 2.97 mmol) was dissolved in 4:1 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 1.05 g (32%) of the title compound as a beige colored solid. Mp: 279-281° C. 1H NMR (DMSO-d6; 400 MHz): δ 1.65 (br s, 6), 2.51 (s, 3), 3.23 (s, 3), 4.01 (br s, 4), 7.02 (s, 1), 7.93, 8.27 (AB q, 4, J=8.3, 8.3), 12.14 (s, 1), 14.38 (s, 1). MS m/z: 371 (M+1 for free base). Anal. Calcd for C19H22N4O2S.HCl.H2O: C, 53.70; H, 5.93; N, 13.19; Cl, 8.34. Found: C, 53.82; H, 5.94; N, 13.08; Cl, 8.49.

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-7ab5e9162f2942e48e6352ad98879a97
Source dataset
uspto-grants-2001_02
Patent number
US06187777B1

Reaction notes

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