2-Fluoro-5-(trifluoromethyl)phenyl isocyanate → HCID 178513851, compound

HRID 1668338Notes

Reaction equation

HRID 1668338 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]([F:11])([F:10])[F:9])=[CH:4][C:3]=1[N:12]=[C:13]=[O:14].[NH2:15][C:16]1[CH:17]=[C:18]([CH:30]=[CH:31][CH:32]=1)[CH2:19][CH2:20][NH:21][C:22]1[C:23]([C:27]([NH2:29])=[O:28])=[N:24][NH:25][CH:26]=1>C1COCC1.C(OCC)(=O)C>[F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]([F:11])([F:10])[F:9])=[CH:4][C:3]=1[NH:12][C:13](=[O:14])[NH:15][C:16]1[CH:17]=[C:18]([CH:30]=[CH:31][CH:32]=1)[CH2:19][CH2:20][NH:21][C:22]1[C:23]([C:27]([NH2:29])=[O:28])=[N:24][NH:25][CH:26]=1

Participants

5

Reactant 2

HCID 27333802-Fluoro-5-(trifluoromethyl)phenyl isocyanateHCID 178513850HCID 178513850, compound

Product 1

HCID 178513851HCID 178513851, compound

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
20 °C

Procedure

A solution of 0.14 ml of 1-fluoro-2-isocyanato-4-trifluoromethylbenzene is added at 20° C. to a solution of 0.25 g of 4-[(3-aminobenzyl)methylamino]-1H-pyrazole-3-carboxamide in 25 ml of anhydrous THF. The reaction medium is stirred for 12 hours at 20° C. and then diluted with 100 ml of ethyl acetate. The organic phase is washed with 50 ml of distilled water, and is then separated out by settling of the phases, dried over magnesium sulfate and evaporated to dryness under reduced pressure. The residue obtained is chromatographed on a column of silica (15 g of Merck cartridge silica with a particle size of 15 to 45 μm, column diameter 2.2 cm, 5 ml fractions, flow rate of 10 ml/min, eluent 95/5 dichloromethane/methanol—by volume). Fractions 35 to 95 are combined and evaporated to dryness under reduced pressure. 0.02 g of 4-({3-[3-(2-fluoro-5-trifluoromethylphenyl)ureido]benzyl}methylamino)-1H-pyrazole-3-carboxamide is obtained in the form of a solid. ([M+H]+): 451). RT: 3.55 min (Method A).

Workup

  1. washThe organic phase is washed with 50 ml of distilled water
  2. customis then separated out
  3. dry with materialdried over magnesium sulfate
  4. customevaporated to dryness under reduced pressure
  5. customThe residue obtained
  6. customis chromatographed on a column of silica (15 g of Merck cartridge silica with a particle size of 15 to 45 μm, column diameter 2.2 cm, 5 ml fractions, flow rate of 10 ml/min, eluent 95/5 dichloromethane/methanol—by volume)
  7. customevaporated to dryness under reduced pressure

Sources & evidence

ORD record
ord-897237dbeaf943e3a9b38e3580f45d3a
Source dataset
uspto-grants-2011_08
Patent number
US07989439B2

Reaction notes

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