Hydrochloric Acid → 4-(4,4-Dimethyl-5-oxo-2-thioxo-3-p-tolyl-imidazolidin-1-yl)-phthalonitrile

HRID 2407525Notes

Reaction equation

HRID 2407525 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)[CH:20]=1)([CH3:17])[CH3:16])#N.C([OH:32])C.Cl.[CH3:34][N:35](C=O)C>>[CH3:16][C:15]1([CH3:17])[C:13](=[O:32])[N:10]([C:9]2[CH:8]=[C:7]([C:34]#[N:35])[C:4](=[CH:3][CH:2]=2)[C:5]#[N:6])[C:11](=[S:12])[N:18]1[C:19]1[CH:20]=[CH:21][C:22]([CH3:23])=[CH:27][CH:28]=1

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 498411114-(4,4-Dimethyl-5-oxo-2-thioxo-3-p-tolyl-imidazolidin-1-yl)-phthalonitrileYield 8.3%

Conditions

Temperature
150 °C

Procedure

A mixture of 3k (370 mg, 2 mmol, prepared by a method similar to the synthesis of 3d) and 6g (348 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 24, 60 mg, 8.3% yield) as a yellow solid. 1H NMR (400 MHz, CDCl3) δ 8.03 (s, 1H), 7.93 (m, 2H), 7.35 (d, J=8 Hz, 2H), 7.16 (d, J=8 Hz, 2H), 2.44 (s, 3H), 1.58 (s, 6H). ESI-MS (M+H)+: 361.

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-bbd1a34171a9484cb9a784dbf0882539
Source dataset
uspto-grants-2014_08
Patent number
US08809550B2

Reaction notes

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