4-Pyridinecarbothioamide → 4-(4-Fluorophenyl)-5-(4-methylthiophenyl)-2-(4-pyridyl)thiazole

HRID 1378566Notes

Reaction equation

HRID 1378566 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8](=O)[CH:9]([C:11]2[CH:16]=[CH:15][C:14]([S:17][CH3:18])=[CH:13][CH:12]=2)Br)=[CH:4][CH:3]=1.[C:20]([NH2:28])(=[S:27])[C:21]1[CH:26]=[CH:25][N:24]=[CH:23][CH:22]=1>C(#N)C>[F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[N:28]=[C:20]([C:21]3[CH:26]=[CH:25][N:24]=[CH:23][CH:22]=3)[S:27][C:9]=2[C:11]2[CH:16]=[CH:15][C:14]([S:17][CH3:18])=[CH:13][CH:12]=2)=[CH:4][CH:3]=1

Participants

4

Reactant 2

HCID 27237884-PyridinecarbothioamideHCID 541605321-(4-Fluorophenyl)-2-(4-methylthiophenyl)-2-bromoethanone2×

Product 1

HCID 543496594-(4-Fluorophenyl)-5-(4-methylthiophenyl)-2-(4-pyridyl)thiazole

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

A solution of the intermediate from Example 1, Step 3, 1-(4-fluorophenyl)-2-(4-methylthiophenyl)-2-bromoethanone, (1.58 g, 4.66 mmol) and thioisonicotinamide (670 mg, 4.84 mmol) in 25 mL of acetonitrile was heated to reflux for 23 hours. The solution was filtered, concentrated in vacuo and the residue taken up in dichloromethane. The dichloromethane solution was washed with sat. aq. NaHCO3, and brine, dried over anhydrous MgSO4, filtered and concentrated in vacuo to give a brown oil that was purified by flash chromatography on silica gel eluting with 20% ethyl acetate in hexane to provide the desired thiazole as an oil that solidified upon standing (640 mg, 36%): mp 107°-109° C. 1H NMR (CDCl3) 300 MHz 8.75 (br s, 2H), 7.85 (d, J=5.9 Hz, 2H), 7.56 (m, 2H), 7.26 (d, J=8.5 Hz, 2H), 7.22 (d, J=8.5 Hz, 2H), 7.01 (t, J=8.5 Hz, 2H), 2.50 (s, 3H); 19F NMR (CDCl3) -113.23 (m). High resolution mass spectrum Calc'd. for C21H15FN2S2 : 379.0661. Found: 379.0691.

Workup

  1. temperatureto reflux for 23 hours
  2. filtrationThe solution was filtered
  3. concentrationconcentrated in vacuo
  4. washThe dichloromethane solution was washed with sat. aq. NaHCO3, and brine
  5. dry with materialdried over anhydrous MgSO4
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo
  8. customto give a brown oil that
  9. customwas purified by flash chromatography on silica gel eluting with 20% ethyl acetate in hexane

Sources & evidence

ORD record
ord-b3574d6ab1ed41fdbe77679e1c62c2ad
Source dataset
uspto-grants-1997_09
Patent number
US05668161

Reaction notes

Loading…