N-bromobutanimide → [2-Amino-4-(4-fluoro-phenyl)-thiazol-5-yl]-(4-fluoro-phenyl)-methanone

HRID 2368426Notes

Reaction equation

HRID 2368426 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8](=O)[CH2:9][C:10]([C:12]2[CH:17]=[CH:16][C:15]([F:18])=[CH:14][CH:13]=2)=[O:11])=[CH:4][CH:3]=1.C1C(=O)N(Br)C(=O)C1.[NH2:28][C:29]([NH2:31])=[S:30]>C(O)C>[NH2:31][C:29]1[S:30][C:9]([C:10]([C:12]2[CH:17]=[CH:16][C:15]([F:18])=[CH:14][CH:13]=2)=[O:11])=[C:8]([C:5]2[CH:6]=[CH:7][C:2]([F:1])=[CH:3][CH:4]=2)[N:28]=1

Participants

5

Reactant 3

HCID 67184N-bromobutanimideHCID 738961,3-Propanedione, 1,3-bis(4-fluorophenyl)-HCID 2723790Thiourea

Product 1

HCID 14435315[2-Amino-4-(4-fluoro-phenyl)-thiazol-5-yl]-(4-fluoro-phenyl)-methanone

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

1,3-Bis-(4-fluoro-phenyl)-propane-1,3-dione and NBS (1.05 eq) were heated neat at 60° C. for 10 minutes then cooled. The resulting mixture was dissolved in ethanol (0.2 M) and treated with thiourea (1.5 eq). It was heated at reflux for 15 hours and cooled to room temperature. It was evaporated to dryness and the residue was partioned between EtOAc and saturated NaHCO3. Organic fraction was dried over MgSO4, filtered and concentrated. The title compound was collected by trituration with heptanes. 1H NMR (400 MHz, DMSO-d6) 6.86-7.01 (m, 4H) 7.22-7.32 (m, 2H) 7.35-7.45 (m, 2H) 8.11 (br. s., 2H). LCMS Method A Rt=1.18 m/z 317.0 (M+1), 315 (M−1).

Workup

  1. temperaturethen cooled
  2. temperatureIt was heated
  3. temperatureat reflux for 15 hours
  4. customIt was evaporated to dryness
  5. dry with materialOrganic fraction was dried over MgSO4
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customThe title compound was collected by trituration with heptanes

Sources & evidence

ORD record
ord-1c576a8d17c5455bb136cf2ff0fd0853
Source dataset
uspto-grants-2014_04
Patent number
US08703761B2

Reaction notes

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