Thionicotinamide → HCID 22912196, compound

HRID 1378585Notes

Reaction equation

HRID 1378585 reaction equation
Br[CH:2]([C:12]1[CH:17]=[CH:16][C:15]([S:18]([CH3:21])(=[O:20])=[O:19])=[CH:14][CH:13]=1)[C:3]([C:5]1[CH:10]=[CH:9][C:8]([F:11])=[CH:7][CH:6]=1)=O.[C:22]([NH2:30])(=[S:29])[C:23]1[CH:28]=[CH:27][CH:26]=[N:25][CH:24]=1>C(#N)C>[F:11][C:8]1[CH:9]=[CH:10][C:5]([C:3]2[N:30]=[C:22]([C:23]3[CH:24]=[N:25][CH:26]=[CH:27][CH:28]=3)[S:29][C:2]=2[C:12]2[CH:17]=[CH:16][C:15]([S:18]([CH3:21])(=[O:20])=[O:19])=[CH:14][CH:13]=2)=[CH:6][CH:7]=1

Participants

4

Reactant 2

HCID 737155ThionicotinamideHCID 112340792-Bromo-1-(4-fluorophenyl)-2-(4-(methylsulfonyl)phenyl)ethanone

Product 1

HCID 22912196HCID 22912196, compoundYield 43.4%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

To a solution of 2-bromo-1-(4-fluorophenyl)-2-(4-methylsulfonylphenyl)ethanone from Step 2 (0.732 g, 1.97 mmol) in acetonitrile (20 mL) in a 50 mL round bottom flask was added thionicotinamide (0.273 g, 1.97 mmol) with stirring. The resulting solution was heated to reflux for 1 hour and additional 2-bromo-1-(4-fluorophenyl)-3-(methylsulfonylphenyl)ethanone (0.031 g, 0.05 mmol) was added and stirred at ruflux for an additional hour. The reaction was cooled to room temperature and concentrated in vacuo yielding an orange semi-solid. This was purified by flash chromatography (2:1 hexane:ethyl acetate with 1% acetic acid). The product fractions were combined, toluene added, and the resulting solution reconcentrated in vacuo yielding 4-(4-fluorophenyl)-5-(4-methylsulfonylphenyl)-2-(3-pyridyl) thiazole as a pale yellow crystalline solid (0.351 g, 43%): mp 143°-146° C. 1H NMR (CDCl3) 400 mHz δ9.20 (d, J=1.81 Hz, 1H), 8.68 (dd, J=1.46, 4.89 Hz, 1H), 8.30 (dr, J=2.00, 9.42 Hz, 1H), 7.91 (d, J=8.55 Hz, 2H), 7.60-7.52 (m, 4H), 7.42 (m, 1), 7.05 (t, J=8.70 Hz, 2H), 3.10 (s, 3H). MS (EI): m/z 410 (M+). HRMS Δ=-4.3

Workup

  1. temperatureThe resulting solution was heated
  2. temperatureto reflux for 1 hour
  3. stirringstirred at ruflux for an additional hour
  4. concentrationconcentrated in vacuo
  5. customyielding an orange semi-solid
  6. customThis was purified by flash chromatography (2:1 hexane:ethyl acetate with 1% acetic acid)
  7. additiontoluene added

Sources & evidence

ORD record
ord-de342e5481784acaa75f83bed1af1cd3
Source dataset
uspto-grants-1997_09
Patent number
US05668161

Reaction notes

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