Benzoic Acid → HCID 68450074, compound

HRID 899961Notes

Reaction equation

HRID 899961 reaction equation
[CH:1]1[C:10]2[C:5](=[C:6]([NH:11][C:12]([CH3:16])([CH3:15])[C:13]#N)[CH:7]=[CH:8][CH:9]=2)[CH:4]=[CH:3][N:2]=1.C(O)(=[O:24])C1C=CC=CC=1.[F:26][C:27]([F:39])([F:38])[S:28][C:29]1[CH:34]=[CH:33][C:32]([N:35]=[C:36]=[O:37])=[CH:31][CH:30]=1>ClC1C=CC=CC=1>[CH:1]1[C:10]2[C:5](=[C:6]([N:11]3[C:12]([CH3:16])([CH3:15])[C:13](=[O:24])[N:35]([C:32]4[CH:31]=[CH:30][C:29]([S:28][C:27]([F:38])([F:26])[F:39])=[CH:34][CH:33]=4)[C:36]3=[O:37])[CH:7]=[CH:8][CH:9]=2)[CH:4]=[CH:3][N:2]=1

Participants

5

Reactant 3

HCID 243Benzoic AcidHCID 27333921-Isocyanato-4-[(trifluoromethyl)sulfanyl]benzeneHCID 684491322-(Isoquinolin-5-ylamino)-2-methylpropionitrile

Product 1

HCID 68450074HCID 68450074, compoundYield 677.5%

Reagents, catalysts & solvents 1

HCID 7964ChlorobenzeneSolvent

Conditions

Temperature
40 °C

Procedure

500 mg (2.4 mmol) of 2-(isoquinolin-5-ylamino)-2-methylpropionitrile, 1.6 mg (0.013 mmol) of benzoic acid and 526 mg (2.4 mmol) of 4-(trifluoromethylthio)phenyl isocyanate in 4 ml of chlorobenzene were refluxed for 2 days. The resulting mixture was filtered and the filtrate was evaporated to dryness. The intermediate imine was separated out by preparative HPLC chromatography (RP 18, acetonitrile, water, 0.01% TFA). 60 mg of the resulting product were stirred for 1 hour at 40° C. with 1N hydrochloric acid. The solvent was evaporated off and the residue was taken up in sodium hydrogen carbonate solution and extracted with ethyl acetate. The combined organic phases were dried and the residue remaining after evaporation was purified by flash chromatography (SiO2, methylene chloride/methanol=98/2), to give 38 mg of the desired product.

Workup

  1. filtrationThe resulting mixture was filtered
  2. customthe filtrate was evaporated to dryness
  3. customThe intermediate imine was separated out by preparative HPLC chromatography (RP 18, acetonitrile, water, 0.01% TFA)
  4. customThe solvent was evaporated off
  5. extractionextracted with ethyl acetate
  6. customThe combined organic phases were dried
  7. customafter evaporation
  8. customwas purified by flash chromatography (SiO2, methylene chloride/methanol=98/2)

Sources & evidence

ORD record
ord-84fd2a0ed0274b55b2a3fe0e3a8042d4
Source dataset
uspto-grants-2008_04
Patent number
US07354933B2

Reaction notes

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