Sodium Methoxide → Dimethyl-{3-[5-(4-trifluoromethyl-phenyl)-1H-[1,2,4]triazol-3-yl]-benzyl}-amine hydrochloride

HRID 1386922Notes

Reaction equation

HRID 1386922 reaction equation
[ClH:1].C(O[C:5](=[NH:16])[C:6]1[CH:11]=[CH:10][C:9]([C:12]([F:15])([F:14])[F:13])=[CH:8][CH:7]=1)C.C[O-].[Na+].[CH3:20][N:21]([CH2:23][C:24]1[CH:25]=[C:26]([CH:31]=[CH:32][CH:33]=1)[C:27]([NH:29][NH2:30])=O)[CH3:22].Cl.CC(O)C>C(O)C.CCOCC>[ClH:1].[CH3:20][N:21]([CH3:22])[CH2:23][C:24]1[CH:33]=[CH:32][CH:31]=[C:26]([C:27]2[N:16]=[C:5]([C:6]3[CH:7]=[CH:8][C:9]([C:12]([F:13])([F:14])[F:15])=[CH:10][CH:11]=3)[NH:30][N:29]=2)[CH:25]=1

Participants

7

Reactant 4

HCID 10942334Sodium MethoxideHCID 21912024Isopropanol hydrochlorideHCID 635713743-Dimethylaminomethyl-benzoic acid hydrazideHCID 68765138Ethyl 4-(trifluoromethyl)benzene-1-carboximidate hydrochloride

Product 1

HCID 21717719Dimethyl-{3-[5-(4-trifluoromethyl-phenyl)-1H-[1,2,4]triazol-3-yl]-benzyl}-amine hydrochlorideYield 10.5%

Reagents, catalysts & solvents 2

HCID 702EthanolSolvent2×HCID 3283Diethyl EtherSolvent

Procedure

To an ethanolic suspension of 4-trifluoromethyl-benzimidic acid ethyl ester hydrochloride salt (761 mg, 3.0 mmol, 1.5 eq.) was added sodium methoxide (162 mg, 3 mmol) in ethanol (20 ml.) and the resulting mixture stirred for 30 min.at r.t. 3-dimethylaminomethyl-benzoic acid hydrazide (386 mg, 2.0 mmol) in ethanol was then added at 20° C., followed by heating to reflux for 16 hrs. Upon cooling, the product mixture was filtered, solvent was evaporated and the residue subjected to preparative reversed-phase HPLC purification using a YMC ODS-AQ column (20×50 mm) and a (0.1% trifluoroacetic acid) water-acetonitrile gradient (25 ml/min. flow rate). The pure fractions were concentrated and the product obtained was converted to the hydrochloride salt in ether by addition of excess 5N HCl/iPrOH solution (1 ml) followed by solvent evaporation and high vacuum drying to afford the title compound (79 mg, 0.21 mmol, 10% yield) as a white foam. MS: m/e=347.4 (M+H+).

Workup

  1. customat r.t
  2. temperatureby heating
  3. temperatureto reflux for 16 hrs
  4. temperatureUpon cooling
  5. filtrationthe product mixture was filtered
  6. customsolvent was evaporated
  7. customreversed-phase HPLC purification
  8. concentrationThe pure fractions were concentrated
  9. customthe product obtained
  10. customfollowed by solvent evaporation and high vacuum
  11. customdrying

Sources & evidence

ORD record
ord-180669cf5f534f7d858f979f1b187d11
Source dataset
uspto-grants-2001_07
Patent number
US06265426B1

Reaction notes

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