N-(tert-Butyl)thiourea → 4-(4-Fluorophenyl)-5-(4-methylsulfonylphenyl)-2-tert-butylaminothiazole

HRID 1378614Notes

Reaction equation

HRID 1378614 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]([NH:26][C:27]([NH2:29])=[S:28])([CH3:25])([CH3:24])[CH3:23]>C(O)C>[F:11][C:8]1[CH:9]=[CH:10][C:5]([C:3]2[N:29]=[C:27]([NH:26][C:22]([CH3:25])([CH3:24])[CH3:23])[S:28][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 737374N-(tert-Butyl)thioureaHCID 112340792-Bromo-1-(4-fluorophenyl)-2-(4-(methylsulfonyl)phenyl)ethanone

Product 1

HCID 229117564-(4-Fluorophenyl)-5-(4-methylsulfonylphenyl)-2-tert-butylaminothiazoleYield 51.3%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

To a solution of 2-bromo-1-(4-fluorophenyl)-2-(4-methylsulfonylphenyl)ethanone (Example 26, Step 2) (0.406 g, 1.09 mmol) in ethanol (11 mL) in a 25 mL round bottom flask was added N-(t-butyl)thiourea (0.144 g, 1.09 mmol) and the solution heated to reflux (14 hours). The reaction was cooled to room temperature. The resulting suspension was concentrated in vacuo, suspended in methylene chloride (100 mL) and washed with NaHCO3 saturated solution (3×10 mL), sodium carbonate solution (10%, 3×20 mL), dried over sodium sulfate, filtered and concentrated. The crude product was recrystallized from methylene chloride and isooctane yielding 4-(4-fluorophenyl)-5-(4-methylsulfonylphenyl)-2-tert-butylaminothiazole (0.226 g, 51%) as a yellow crystalline plates: mp 250°-253° C.; 1HNMR (DMSO d6) 400 mHz 7.78 (d, J=8.32 Hz, 2 H), 7.70 (s, 1 H), 7.46-7.35 (m, 4 H), 7.15 (t, J=9.05 Hz, 2 H), 3.19 (s, 3 H), 1.40 (s, 9 H); MS m/z 405 (M+H). HRMS Δ=4.78 mmu.

Workup

  1. temperaturethe solution heated
  2. temperatureto reflux (14 hours)
  3. concentrationThe resulting suspension was concentrated in vacuo
  4. washwashed with NaHCO3 saturated solution (3×10 mL), sodium carbonate solution (10%, 3×20 mL)
  5. dry with materialdried over sodium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customThe crude product was recrystallized from methylene chloride and isooctane

Sources & evidence

ORD record
ord-851291b2afa343fa939b26b25070e571
Source dataset
uspto-grants-1997_09
Patent number
US05668161

Reaction notes

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