Pyridine → 2-(1-(4-fluorobenzyl)-5-oxo-1H-1,2,4-triazol-4(5H)-yl)-4-methylthiazole-5-carbonitrile

HRID 555017Notes

Reaction equation

HRID 555017 reaction equation
[F:1][C:2]1[CH:23]=[CH:22][C:5]([CH2:6][N:7]2[C:11](=[O:12])[N:10]([C:13]3[S:14][C:15]([C:19]([NH2:21])=O)=[C:16]([CH3:18])[N:17]=3)[CH:9]=[N:8]2)=[CH:4][CH:3]=1.N1C=CC=CC=1.FC(F)(F)C(OC(=O)C(F)(F)F)=O>O1CCOCC1>[F:1][C:2]1[CH:23]=[CH:22][C:5]([CH2:6][N:7]2[C:11](=[O:12])[N:10]([C:13]3[S:14][C:15]([C:19]#[N:21])=[C:16]([CH3:18])[N:17]=3)[CH:9]=[N:8]2)=[CH:4][CH:3]=1

Participants

5

Reactant 3

HCID 1049PyridineHCID 9845Trifluoroacetic anhydrideHCID 441936012-(1-(4-fluorobenzyl)-5-oxo-1H-1,2,4-triazol-4(5H)-yl)-4-methylthiazole-5-carboxamide

Product 1

HCID 579198502-(1-(4-fluorobenzyl)-5-oxo-1H-1,2,4-triazol-4(5H)-yl)-4-methylthiazole-5-carbonitrileYield 63%

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent

Procedure

A mixture of 2-(1-(4-fluorobenzyl)-5-oxo-1H-1,2,4-triazol-4(5H)-yl)-4-methylthiazole-5-carboxamide (0.45 g, 1.35 mmol), pyridine (0.21 g, 2.71 mmol) and trifluoroacetic anhydride (0.57 g, 2.71 mmol) in dioxane (12.0 mL) was heated at reflux for 16 h and concentrated in vacuo to dryness. The residue was purified by flash column chromatography eluted with ethyl acetate in hexane (20%) to afford 2-(1-(4-fluorobenzyl)-5-oxo-1H-1,2,4-triazol-4(5H)-yl)-4-methylthiazole-5-carbonitrile as a colourless solid (0.26 g, 63%): mp 190-192° C.; 1H NMR (300 MHz, DMSO-d6) δ 8.80 (s, 1H), 7.38-7.33 (m, 2H), 7.18-7.12 (m, 2H), 4.97 (s, 2H), 2.49 (s, 3H); 13C NMR (75 MHz, DMSO-d6) δ 162.2 (d), 161.3, 156.0, 150.3, 132.5, 132.4, 130.5 (d), 115.9 (d), 113.3, 97.5, 48.3, 17.2; MS (ES+) m/z 316.9 (M+1).

Workup

  1. temperaturewas heated
  2. temperatureat reflux for 16 h
  3. concentrationconcentrated in vacuo to dryness
  4. customThe residue was purified by flash column chromatography
  5. washeluted with ethyl acetate in hexane (20%)

Sources & evidence

ORD record
ord-eb467a1d20e5479899b2dffc696294f4
Source dataset
uspto-grants-2011_11
Patent number
US08049016B2

Reaction notes

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