Hydrochloric Acid → 4-{4-[7-(4-Cyano-3-trifluoromethylphenyl)-8-oxo-6-thioxo-5,7-diazaspiro[3.4]oct-5-yl]-phenyl}-butyric acid methyl ester

HRID 1192860Notes

Reaction equation

HRID 1192860 reaction equation
[N:1]([C:4]1[CH:11]=[CH:10][C:7]([C:8]#[N:9])=[C:6]([C:12]([F:15])([F:14])[F:13])[CH:5]=1)=[C:2]=[S:3].[C:16]([C:18]1([NH:22][C:23]2[CH:28]=[CH:27][C:26]([CH2:29][CH2:30][CH2:31][C:32]([OH:34])=O)=[CH:25][CH:24]=2)[CH2:21][CH2:20][CH2:19]1)#N.[CH3:35][OH:36].Cl.CN(C=[O:42])C>O>[CH3:35][O:36][C:32](=[O:34])[CH2:31][CH2:30][CH2:29][C:26]1[CH:27]=[CH:28][C:23]([N:22]2[C:2](=[S:3])[N:1]([C:4]3[CH:11]=[CH:10][C:7]([C:8]#[N:9])=[C:6]([C:12]([F:13])([F:15])[F:14])[CH:5]=3)[C:16](=[O:42])[C:18]32[CH2:21][CH2:20][CH2:19]3)=[CH:24][CH:25]=1

Participants

7

Reactant 5

HCID 313Hydrochloric AcidHCID 887MethanolHCID 6228DimethylformamideHCID 116155404-Isothiocyanato-2-(trifluoromethyl)benzonitrileHCID 667220494-(4-(1-Cyanocyclobutylamino)phenyl)butanoic acid

Product 1

HCID 866300064-{4-[7-(4-Cyano-3-trifluoromethylphenyl)-8-oxo-6-thioxo-5,7-diazaspiro[3.4]oct-5-yl]-phenyl}-butyric acid methyl esterYield 79%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Procedure

A mixture of 4-isothiocyanato-2-trifluoromethylbenzonitrile (96) (0.547 g, 2.4 mmol) and 4-[4-(1-Cyanocyclobutylamino)-phenyl]-butyric acid (91) (0.342 g, 1.5 mmol) in dry DMF (2 ml) was stirred at room temperature for 15 hours. To this mixture were added methanol (10 ml) and HCl aq. (5 ml, 2M). The second mixture was refluxed for 3 h. After being cooled to room temperature, the reaction mixture was poured into cold water (10 ml) and extracted with ethyl acetate (3×30 ml). The organic layer was dried over MgSO4, concentrated and chromatographed (dichloromethane) to yield 4-{4-[7-(4-cyano-3-trifluoromethylphenyl)-8-oxo-6-thioxo-5,7-diazaspiro[3.4]oct-5-yl]-phenyl}-butyric acid methyl ester (90) [ND-4] (0.594 g, 1.18 mmol, 79%) as a white powder.

Workup

  1. temperatureThe second mixture was refluxed for 3 h
  2. temperatureAfter being cooled to room temperature
  3. extractionextracted with ethyl acetate (3×30 ml)
  4. dry with materialThe organic layer was dried over MgSO4
  5. concentrationconcentrated
  6. customchromatographed (dichloromethane)

Sources & evidence

ORD record
ord-fcbc5e5d13e74ce9a4f125c431201229
Source dataset
uspto-grants-2014_03
Patent number
US08680291B2

Reaction notes

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