Triethylamine → 3-[4-Methyl-5-(2-trifluoromethyl-benzoyl)-thiazol-2-ylamino]-benzonitrile

HRID 852441Notes

Reaction equation

HRID 852441 reaction equation
N[C:2](=[N:4][C:5]([NH:7][C:8]1[CH:13]=[CH:12][CH:11]=[C:10]([C:14]#[N:15])[CH:9]=1)=[S:6])[CH3:3].Br[CH2:17][C:18]([C:20]1[CH:25]=[CH:24][CH:23]=[CH:22][C:21]=1[C:26]([F:29])([F:28])[F:27])=[O:19].C(N(CC)CC)C>C(O)C.CO>[CH3:3][C:2]1[N:4]=[C:5]([NH:7][C:8]2[CH:9]=[C:10]([CH:11]=[CH:12][CH:13]=2)[C:14]#[N:15])[S:6][C:17]=1[C:18](=[O:19])[C:20]1[CH:25]=[CH:24][CH:23]=[CH:22][C:21]=1[C:26]([F:27])([F:28])[F:29]

Participants

6

Reactant 3

HCID 8471TriethylamineHCID 27784302-Bromo-1-[2-(trifluoromethyl)phenyl]ethan-1-oneHCID 85938104HCID 85938104, compound

Product 1

HCID 865912083-[4-Methyl-5-(2-trifluoromethyl-benzoyl)-thiazol-2-ylamino]-benzonitrileYield 12%

Reagents, catalysts & solvents 2

HCID 702EthanolSolventHCID 887MethanolSolvent

Procedure

To a mixture of 801 mg (5 mmol) 3-cyanophenylthioisocyanate in 5 ml 1N NaOH at 0° C. was added 473 mg acetamidine hydrochloride in 10 ml THF and allowed to stir at 0° C. for 16 h. The mixture was extracted with ethylacetate and the combined organic layers were dried with MgSO4 and evaporated to dryness. The residue was purified by flash column chromatography on silica eluting with ethylacetate/cyclohexane 1:2 to yield 510 mg (47%) of 1-(1-Amino-ethylidene)-3-(3-cyano-phenyl)-thiourea. (MS (m/e): 219.2 (M+H, 100%). A mixture of 50 mg (0.23 mmol) 1-(1-Amino-ethylidene)-3-(3-cyano-phenyl)-thiourea, 92 mg (0.345 mmol) 2-Bromo-1-(2-trifluoromethyl-phenyl)-ethanone and 48 ul triethylamine in 1 ml ethanol was stirred for 16 h at room temperature. The mixtures were diluted with methanol and directly subjected to preparative HPLC separation on reversed phase eluting with an acetonitrile/water gradient. Evaporation of the product fractions yielded 10.4 mg (12%) of the title compound. (MS (m/e): 386.2 (M−H, 100%)

Workup

  1. customHPLC separation on reversed phase
  2. washeluting with an acetonitrile/water gradient
  3. customEvaporation of the product fractions

Sources & evidence

ORD record
ord-ee3d7bf53f5d45b2ab40bf5de6c0d939
Source dataset
uspto-grants-2007_08
Patent number
US07253197B2

Reaction notes

Loading…