Hydrochloric Acid → 4-[3-(3-Fluoro-4-methyl-phenyl)-4,4-dimethyl-5-oxo-2-thioxo-imidazolidin-1-yl]-phthalonitrile

HRID 2407526Notes

Reaction equation

HRID 2407526 reaction equation
Cl[C:2]1[CH:3]=[C:4]([CH:7]=[CH:8][C:9]=1[N:10]=[C:11]=[S:12])[C:5]#[N:6].[C:13]([C:15]([NH:18][C:19]1[CH:28]=[CH:27][C:22]([C:23](NC)=O)=[C:21]([F:29])[CH:20]=1)([CH3:17])[CH3:16])#N.C([OH:32])C.Cl.[CH3:34][N:35](C=O)C>>[F:29][C:21]1[CH:20]=[C:19]([N:18]2[C:15]([CH3:16])([CH3:17])[C:13](=[O:32])[N:10]([C:9]3[CH:8]=[C:7]([C:34]#[N:35])[C:4](=[CH:3][CH:2]=3)[C:5]#[N:6])[C:11]2=[S:12])[CH:28]=[CH:27][C:22]=1[CH3:23]

Participants

6

Reactant 5

HCID 313Hydrochloric AcidHCID 702EthanolHCID 6228DimethylformamideHCID 183163923-Chloro-4-isothiocyanato-benzonitrileHCID 592965474-[(2-Cyanopropan-2-yl)amino]-2-fluoro-N-methylbenzamide

Product 1

HCID 498412244-[3-(3-Fluoro-4-methyl-phenyl)-4,4-dimethyl-5-oxo-2-thioxo-imidazolidin-1-yl]-phthalonitrileYield 19.8%

Conditions

Temperature
150 °C

Procedure

A mixture of 3k (370 mg, 2 mmol, prepared by a method similar to the synthesis of 3d) and 6h (384 mg, 2 mmol, prepared by a method similar to the synthesis of 6b) in DMF (10 mL) was heated under microwave irradiation at 150° C. for 5 h. To this mixture was added ethanol (10 mL) and aqueous HCl solution (2N, 5 mL). The resulting mixture was heated at reflux for 1 h. The solution was poured into ice-cold water and extracted with ethyl acetate (3×30 mL). The organic layers were combined, dried over MgSO4, and concentrated in vacuo. The residue was purified with Pre-HPLC, affording the title compound (Example 25, 150 mg, 19.8% yield) as a yellow solid. 1H NMR (400 MHz, CDCl3) δ 8.01 (s, 1H), 7.93-7.91 (m, 2H), 7.26-7.09 (m, 3H), 2.35 (s, 3H), 1.58 (s, 6H). ESI-MS (M+H)+: 379.

Workup

  1. temperatureThe resulting mixture was heated
  2. temperatureat reflux for 1 h
  3. additionThe solution was poured into ice-cold water
  4. extractionextracted with ethyl acetate (3×30 mL)
  5. dry with materialdried over MgSO4
  6. concentrationconcentrated in vacuo
  7. customThe residue was purified with Pre-HPLC

Sources & evidence

ORD record
ord-6f6ca620ef684251bd19b7d1e3fcba8b
Source dataset
uspto-grants-2014_08
Patent number
US08809550B2

Reaction notes

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