Hydrochloric Acid → HCID 15951528, compound

HRID 245025Notes

Reaction equation

HRID 245025 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].[F:16][C:17]1[CH:22]=[C:21]([OH:23])[CH:20]=[CH:19][C:18]=1[NH:24][C:25]1([C:29]#N)[CH2:28][CH2:27][CH2:26]1.C[OH:32].Cl>CN(C=O)C.CC(C)=O.ClCCl.O>[F:16][C:17]1[CH:22]=[C:21]([OH:23])[CH:20]=[CH:19][C:18]=1[N:24]1[C:2](=[S:3])[N:1]([C:4]2[CH:11]=[CH:10][C:7]([C:8]#[N:9])=[C:6]([C:12]([F:13])([F:15])[F:14])[CH:5]=2)[C:29](=[O:32])[C:25]21[CH2:28][CH2:27][CH2:26]2

Participants

9

Reactant 4

HCID 313Hydrochloric AcidHCID 887MethanolHCID 116155404-Isothiocyanato-2-(trifluoromethyl)benzonitrileHCID 67132120HCID 67132120, compound

Product 1

HCID 15951528HCID 15951528, compoundYield 56%

Reagents, catalysts & solvents 4

HCID 180AcetoneSolventHCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent

Procedure

A mixture of 4-isothiocyanato-2-trifluoromethylbenzonitrile (1a) (0.228 g, 1.0 mmol) and 1-(2-fluoro-4-hydroxyphenylamino)-cyclobutanecarbonitrile (53b) (0.145 g, 0.7 mmol) in dry DMF (2 ml) was stirred at room temperature for 24 hours. To this mixture were added methanol (10 ml) and aq. 2M HCl (2 ml). The second mixture was refluxed for 1 hour. After being cooled to room temperature, the reaction mixture was poured into cold water (10 ml) and extracted with ethyl acetate (50 ml). The organic layer was dried over MgSO4, concentrated and chromatographed (dichloromethane pure and then dichloromethane:acetone, 90:10) to yield 4-[5-(2-fluoro-4-hydroxyphenyl)-8-oxo-6-thioxo-5,7-diazaspiro[3.4]oct-7-yl]-2-trifluoromethylbenzonitrile (53c) [RD163] (3.17 g, 0.39 mmol, 56%), the structure of which is illustrated in Formula 29, as a off-white powder.

Workup

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

Sources & evidence

ORD record
ord-c166ae5bf93e4236a1e07679202f61d1
Source dataset
uspto-grants-2014_02
Patent number
US08658681B2

Reaction notes

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