Hydrochloric Acid → HCID 86609864, compound

HRID 2273928Notes

Reaction equation

HRID 2273928 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:31]=[CH:30][C:26]([C:27](O)=[O:28])=[CH:25][CH:24]=2)[CH2:21][CH2:20][CH2:19]1)#N.[CH3:32][OH:33].Cl.CN(C=[O:39])C>O>[CH3:32][O:33][C:27](=[O:28])[C:26]1[CH:30]=[CH:31][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:39])[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 67132172HCID 67132172, compound

Product 1

HCID 86609864HCID 86609864, compoundYield 12%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Conditions

Temperature
60 °C

Procedure

A mixture of 4-isothiocyanato-2-trifluoromethylbenzonitrile (1a) (0.51 g, 2.22 mmol) and 4-(1-cyanocyclobutylamino)benzoic acid (51a) (0.343 g, 1.59 mmol) in DMF (2 ml) was heated under microwave irradiation at 60° C. and stirred for 16 hours. To this mixture were added methanol (10 ml) and aq. 2M HCl (5 ml). The second mixture was refluxed for 12 hours. After being cooled to room temperature, the reaction mixture was poured into cold water (20 ml) and extracted with ethyl acetate (3×30 ml). The organic layer was dried over MgSO4, concentrated and chromatographed (dichloromethane:acetone, 95:5) to yield 4-[7-(4-cyano-3-trifluoromethylphenyl)-8-oxo-6-thioxo-5,7-diazaspiro[3.4]oct-5-yl]-benzoic acid methyl ester (51b) [RD159] (0.09 g, 0.196 mmol, 12%), the structure of which is illustrated in Formula 25, as a white powder and N-(3-cyano-4-trifluoromethylphenyl)-4-[7-(4-cyano-3-trifluoromethylphenyl)-8-oxo-6-thioxo-5,7-diazaspiro[3.4]oct-5-yl]benzamide (51b′) [RD160] (0.28 g, 0.45 mmol, 29%), the structure of which is illustrated in Formula 26, as a white powder.

Workup

  1. temperatureThe second mixture was refluxed for 12 hours
  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:acetone, 95:5)

Sources & evidence

ORD record
ord-e56eace645854b5a81fc3c073af6478a
Source dataset
uspto-grants-2015_09
Patent number
US09126941B2

Reaction notes

Loading…