Hydrochloric Acid → HCID 86609857, compound

HRID 2273916Notes

Reaction equation

HRID 2273916 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][C:30]([OH:32])=O)=[CH:25][CH:24]=2)[CH2:21][CH2:20][CH2:19]1)#N.[CH3:33][OH:34].Cl.CN(C=[O:40])C>CC(C)=O.ClCCl.O>[CH3:33][O:34][C:30](=[O:32])[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:40])[C:18]32[CH2:21][CH2:20][CH2:19]3)=[CH:24][CH:25]=1

Participants

9

Reactant 5

HCID 313Hydrochloric AcidHCID 887MethanolHCID 6228DimethylformamideHCID 116155404-Isothiocyanato-2-(trifluoromethyl)benzonitrileHCID 67132001HCID 67132001, compound

Product 1

HCID 86609857HCID 86609857, compoundYield 56%

Reagents, catalysts & solvents 3

HCID 180AcetoneSolventHCID 962WaterSolventHCID 6344DichloromethaneSolvent

Procedure

A mixture of 4-isothiocyanato-2-trifluoromethylbenzonitrile (1a) (0.638 g, 2.8 mmol) and [4-(1-cyanocyclobutylamino)phenyl]acetic acid (46a) (0.46 g, 2.0 mmol) in DMF (5 ml) was stirred at room temperature for 15 hours. To this mixture were added methanol (20 ml) and aq. 2N HCl (10 ml). The second mixture was refluxed for 1 h. After being cooled to room temperature, the reaction mixture was poured into cold water (10 ml) and extracted with ethyl acetate (3×50 ml). The organic layer was dried over MgSO4, concentrated and chromatographed (dichloromethane pure and then dichloromethane:acetone, 95:5) to yield {4-[7-(4-cyano-3-trifluoromethylphenyl)-8-oxo-6-thioxo-5,7-diaza-spiro[3.4]oct-5-yl]phenyl}acetic acid methyl ester (46b) [RD146] (0.532 g, 1.124 mmol, 56%), the structure of which is illustrated in Formula 15, as a white powder.

Workup

  1. temperatureThe second mixture was refluxed for 1 h
  2. temperatureAfter being cooled to room temperature
  3. extractionextracted with ethyl acetate (3×50 ml)
  4. dry with materialThe organic layer was dried over MgSO4
  5. concentrationconcentrated
  6. customchromatographed (dichloromethane pure

Sources & evidence

ORD record
ord-c9ac3bd9020e42689d2903d8aa210539
Source dataset
uspto-grants-2015_09
Patent number
US09126941B2

Reaction notes

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