Dimethylformamide → 6-(4-(trifluoromethoxy)phenyl)-2-(2-(5-(trifluoromethyl)pyrimidin-2-yloxy)ethyl)-[1,2,4]triazolo[4,3-a]pyridin-3(2H)-one

HRID 2368022Notes

Reaction equation

HRID 2368022 reaction equation
[OH:1][CH2:2][CH2:3][N:4]1[C:23](=[O:24])[N:7]2[CH:8]=[C:9]([C:12]3[CH:17]=[CH:16][C:15]([O:18][C:19]([F:22])([F:21])[F:20])=[CH:14][CH:13]=3)[CH:10]=[CH:11][C:6]2=[N:5]1.[H-].[Na+].Cl[C:28]1C=[CH:32][C:31]([C:34]([F:37])([F:36])[F:35])=[CH:30][N:29]=1.C[N:39](C=O)C>>[F:21][C:19]([F:20])([F:22])[O:18][C:15]1[CH:16]=[CH:17][C:12]([C:9]2[CH:10]=[CH:11][C:6]3[N:7]([C:23](=[O:24])[N:4]([CH2:3][CH2:2][O:1][C:28]4[N:39]=[CH:32][C:31]([C:34]([F:37])([F:36])[F:35])=[CH:30][N:29]=4)[N:5]=3)[CH:8]=2)=[CH:13][CH:14]=1

Participants

5

Reactant 4

HCID 6228DimethylformamideHCID 24758Sodium hydrideHCID 923422-Chloro-5-(trifluoromethyl)pyridineHCID 666328372-(2-hydroxyethyl)-6-(4-(trifluoromethoxy)phenyl)-[1,2,4]triazolo[4,3-a]pyridin-3(2H)-one

Product 1

HCID 866608716-(4-(trifluoromethoxy)phenyl)-2-(2-(5-(trifluoromethyl)pyrimidin-2-yloxy)ethyl)-[1,2,4]triazolo[4,3-a]pyridin-3(2H)-one

Procedure

6-(4-(trifluoromethoxy)phenyl)-[1,2,4]triazolo[4,3-a]pyridin-3(2H)-one (825 mg) from Example 1 above was dissolved in DMA (10 mL), 2-bromoethanol (1.0 g) and potassium carbonate (235 mg) were added. Heated overnight at 110° C. Filtered, concentrated, and purified by chromatography (ethyl acetate/hexanes). 2-(2-hydroxyethyl)-6-(4-(trifluoromethoxy)phenyl)-[1,2,4]triazolo[4,3-a]pyridin-3(2H)-one was obtained as white solid (830 mg). m/z (ESI)=340.0 (base peak, M+H+); 701.1 (2M+Na+). 2-(2-hydroxyethyl)-6-(4-(trifluoromethoxy)phenyl)-[1,2,4]triazolo[4,3-a]pyridin-3(2H)-one (50 mg) was dissolved in dry DMF and the NaH suspension (12 mg, 60% in oil) was added, followed shortly by 2-chloro-5-trifluoromethylpyridine (54 mg). Concentrated and purified on silica using ethyl acetate/hexanes gradient to obtain compound 180 as a white solid (71 mg). m/z (ESI)=486.1 (base peak, M+H+); 508.1 (M+Na+); 993.2 (2M+Na+). 1H NMR (δ, CDCl3, 400 MHz) 8.75 (s, 2H); 7.98 (d, 1H); 7.53 (d, 2H); 7.40-7.30 (m, 3H); 7.18 (d, 1H); 4.90 (t, 2H); 4.49 (t, 2H). 19F NMR (δ, CDCl3, 376 MHz) −58.36 (s, 1F); −61.99 (s, 1F).

Workup

  1. concentrationConcentrated
  2. custompurified on silica

Sources & evidence

ORD record
ord-073b4d03990b4a779c488548564be34f
Source dataset
uspto-grants-2014_04
Patent number
US08703759B2

Reaction notes

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