Sodium ethoxide → 5-(3-benzyloxy-4-methoxy-phenyl)-3-(3-pyrrolidin-1-ylmethyl-phenyl)-1H-[1,2,4]triazole hydrochloride

HRID 1386929Notes

Reaction equation

HRID 1386929 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+].[CH2:21]([O:28][C:29]1[CH:30]=[C:31]([CH:36]=[CH:37][C:38]=1[O:39][CH3:40])[C:32]([NH:34]N)=O)[C:22]1[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=1.Cl.CCOCC>C(O)C>[ClH:1].[CH2:21]([O:28][C:29]1[CH:30]=[C:31]([C:32]2[NH:34][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:36]=[CH:37][C:38]=1[O:39][CH3:40])[C:22]1[CH:23]=[CH:24][CH:25]=[CH:26][CH:27]=1

Participants

6

Reactant 4

HCID 2723922Sodium ethoxideHCID 10953452Ether hydrochlorideHCID 217177063-Pyrrolidin-1-ylmethyl-benzamidine hydrochloride saltHCID 698307613-Benzyloxy-4-methoxy-benzoic acid hydrazide

Product 1

HCID 211803505-(3-benzyloxy-4-methoxy-phenyl)-3-(3-pyrrolidin-1-ylmethyl-phenyl)-1H-[1,2,4]triazole hydrochlorideYield 89%

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 ethanol (15 ml) was added 1.2N NaOEt in ethanol (3.4 ml, 4 eq.) over 3 min. and stirring was then continued for 30 min. at r.t. 3-Benzyloxy-4-methoxy-benzoic acid hydrazide (272 mg, 1 mmol) in ethanol was added at 20° C. and the resulting mixture was heated to reflux for 50 hrs. Upon cooling, the product mixture was filtered, the solvent was evaporated and the residue chromatographed over 20 g SiO2 (Merck 230-400 mesh) with CH2Cl2-MeOH (2M NH3) 96:4 affording a solid. 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 dried under high vacuum at 30° C. overnight affording the title compound (326 mg, 89% yield) as a yellow solid. MS: m/e=441.6 (M+H+)

Workup

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

Sources & evidence

ORD record
ord-03b5651e157d4515a14bc201c9e93635
Source dataset
uspto-grants-2001_07
Patent number
US06265426B1

Reaction notes

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