Hydrochloric Acid → 4-[7-[4-cyano-3-(trifluoromethyl)phenyl]-8-oxo-6-sulfanylidene-5,7-diazaspiro[3.4]octan-5-yl]-2-fluoro-N-methylbenzamide

HRID 2233720Notes

Reaction equation

HRID 2233720 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].[CH3:16][NH:17][C:18](=[O:33])[C:19]1[CH:24]=[CH:23][C:22]([NH:25][C:26]2([C:30]#N)[CH2:29][CH2:28][CH2:27]2)=[CH:21][C:20]=1[F:32].C[OH:35].Cl>CN(C=O)C.O>[CH3:16][NH:17][C:18](=[O:33])[C:19]1[CH:24]=[CH:23][C:22]([N:25]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:30](=[O:35])[C:26]32[CH2:29][CH2:28][CH2:27]3)=[CH:21][C:20]=1[F:32]

Participants

7

Reactant 4

HCID 313Hydrochloric AcidHCID 887MethanolHCID 116155404-Isothiocyanato-2-(trifluoromethyl)benzonitrileHCID 441395204-[(1-Cyanocyclobutyl)amino]-2-fluoro-N-methylbenzamide

Product 1

HCID 119577564-[7-[4-cyano-3-(trifluoromethyl)phenyl]-8-oxo-6-sulfanylidene-5,7-diazaspiro[3.4]octan-5-yl]-2-fluoro-N-methylbenzamideYield 57%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Conditions

Temperature
80 °C

Procedure

A mixture of 4-isothiocyanato-2-trifluoromethylbenzonitrile (1a) (2.16 g, 9.47 mmol) and N-methyl-4-(1-cyanocyclobutylamino)-2-fluorobenzamide (52c) (1.303 g, 5.27 mmol) in DMF (20 ml) was heated under microwave irradiation at 80° C. for 16 hours. To this mixture was added methanol (50 ml) and aq. 2N HCl (20 ml). The second mixture was refluxed for 3 hours. After being cooled to room temperature, the reaction mixture was poured into cold water (100 ml) and extracted with ethyl acetate (150 ml). The organic layer was dried over MgSO4, concentrated and chromatographed (dichloromethane:acetone, 95:5) to yield N-methyl-4-[7-(4-cyano-3-trifluoromethylphenyl)-8-oxo-6-thioxo-5,7-diaza-spiro[3.4]oct-5-yl]-2-fluorobenzamide (52d) [RD162](1.43 g, 3.0 mmol, 57%), the structure of which is illustrated in Formula 28, as a yellow powder.

Workup

  1. temperatureThe second mixture was refluxed for 3 hours
  2. temperatureAfter being cooled to room temperature
  3. extractionextracted with ethyl acetate (150 ml)
  4. dry with materialThe organic layer was dried over MgSO4
  5. concentrationconcentrated
  6. customchromatographed (dichloromethane:acetone, 95:5)

Sources & evidence

ORD record
ord-59290d1348fa4f6aa6e70687cc4c0d01
Source dataset
uspto-grants-2010_05
Patent number
US07709517B2

Reaction notes

Loading…