4-Methylsulfanylbenzohydrazide → 5-(4-Methylsulfanyl-phenyl)-3-(3-pyrrolidin-1-ylmethyl-phenyl)-1H-[1,2,4]triazole hydrochloride salt

HRID 1386927Notes

Reaction equation

HRID 1386927 reaction equation
[ClH:1].[N:2]1([CH2:7][C:8]2[CH:9]=[C:10]([CH:14]=[CH:15][CH:16]=2)[C:11]([NH2:13])=[NH:12])[CH2:6][CH2:5][CH2:4][CH2:3]1.CC[O-].[Na+].[CH3:21][S:22][C:23]1[CH:32]=[CH:31][C:26]([C:27]([NH:29]N)=O)=[CH:25][CH:24]=1.Cl.CCOCC>C(O)C>[ClH:1].[CH3:21][S:22][C:23]1[CH:32]=[CH:31][C:26]([C:27]2[NH:29][N:13]=[C:11]([C:10]3[CH:14]=[CH:15][CH:16]=[C:8]([CH2:7][N:2]4[CH2:6][CH2:5][CH2:4][CH2:3]4)[CH:9]=3)[N:12]=2)=[CH:25][CH:24]=1

Participants

6

Reactant 4

HCID 2654354-MethylsulfanylbenzohydrazideHCID 2723922Sodium ethoxideHCID 10953452Ether hydrochlorideHCID 217177063-Pyrrolidin-1-ylmethyl-benzamidine hydrochloride salt

Product 1

HCID 211803715-(4-Methylsulfanyl-phenyl)-3-(3-pyrrolidin-1-ylmethyl-phenyl)-1H-[1,2,4]triazole hydrochloride saltYield 52%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent3×

Procedure

To a stirred ethanolic suspension of 3-pyrrolidin-1-ylmethyl-benzamidine hydrochloride salt (1:2) (414 mg, 1.5 mmol, 1.5 eq.) in 15 ml ethanol was added over 3 minutes 1.2N NaOEt in ethanol (3.4 ml, 4 eq.) and stirring was continued for 30 min. at r.t. 4-Methylsulfanyl-benzoic acid hydrazide (182 mg, 1 mmol) in ethanol at 20° C. was then added and the mixture heated to reflux for 50 hrs. Upon cooling the product mixture was filtered, solvent evaporated and residue chromatographed over 20 g SiO2 (Merck 230-400 mesh) with CH2Cl2-MeOH (2M NH3) 96:4, affording a foam after solvent evaporation. This material was dissolved in ethanol at r.t. and an excess 2N HCl/ether solution (1.0 ml, 2 mmol) was added. After 30 min. the solvent was evaporated and the residue was dried overnight under high vacuum at 30° C. affording the title compound (200 mg, 52% yield) as a yellow foam. MS: m/e=351.5 (M+H+).

Workup

  1. temperaturethe mixture heated
  2. temperatureto reflux for 50 hrs
  3. temperatureUpon cooling the product mixture
  4. filtrationwas filtered
  5. customsolvent evaporated
  6. customresidue chromatographed over 20 g SiO2 (Merck 230-400 mesh) with CH2Cl2-MeOH (2M NH3) 96:4
  7. customaffording a foam
  8. customafter solvent evaporation
  9. dissolutionThis material was dissolved in ethanol at r.t.
  10. customAfter 30 min. the solvent was evaporated
  11. customthe residue was dried overnight under high vacuum at 30° C.

Sources & evidence

ORD record
ord-76909db10db046fb90d2db682be720ba
Source dataset
uspto-grants-2001_07
Patent number
US06265426B1

Reaction notes

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