1H-1,2,4-Triazole → HCID 86604528, compound

HRID 1858849Notes

Reaction equation

HRID 1858849 reaction equation
[NH:1]1[CH:5]=[N:4][CH:3]=[N:2]1.[H-].[Na+].[CH2:8]([O:15][CH2:16][CH2:17][CH2:18][O:19][C:20]1[CH:25]=[CH:24][C:23]([CH:26]2[CH:31]([O:32][CH2:33][C:34]3[CH:43]=[CH:42][C:41]4[C:36](=[CH:37][CH:38]=[CH:39][CH:40]=4)[CH:35]=3)[CH2:30][N:29]([C:44]([O:46][C:47]([CH3:50])([CH3:49])[CH3:48])=[O:45])[CH2:28][CH:27]2[CH2:51]OS(C)(=O)=O)=[CH:22][CH:21]=1)[C:9]1[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=1>CN(C=O)C>[CH2:8]([O:15][CH2:16][CH2:17][CH2:18][O:19][C:20]1[CH:21]=[CH:22][C:23]([CH:26]2[CH:27]([CH2:51][N:1]3[CH:5]=[N:4][CH:3]=[N:2]3)[CH2:28][N:29]([C:44]([O:46][C:47]([CH3:48])([CH3:50])[CH3:49])=[O:45])[CH2:30][CH:31]2[O:32][CH2:33][C:34]2[CH:43]=[CH:42][C:41]3[C:36](=[CH:37][CH:38]=[CH:39][CH:40]=3)[CH:35]=2)=[CH:24][CH:25]=1)[C:9]1[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=1

Participants

5

Reactant 3

HCID 92571H-1,2,4-TriazoleHCID 24758Sodium hydrideHCID 86604527HCID 86604527, compound

Product 1

HCID 86604528HCID 86604528, compoundYield 77%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

A solution of 22 mg (0.32 mmol) of 1,2,4-triazole in 5 ml of DMF was cooled to 0° C. and treated with 15 mg (0.29 mmol) of sodium hydride (50% dispersion in refined oil). Subsequently, the mixture was left to warm to room temperature and was stirred for a further 1 hour. 70 mg (0.105 mmol) of tert-butyl (3SR,4RS,5RS)-4-[4-(3-benzyloxy-propoxy)-phenyl]-3-methane-sulphonyloxymethyl-5-(naphthalen-2-ylmethoxy)-piperidine-1-carboxylate were added to this solution. The reaction mixture was heated to 100° C. for 24 hours. For the working-up, the reaction mixture was evaporated under reduced pressure, the residue was partitioned between water and methylene chloride and the organic phase was separated, dried over sodium sulphate and evaporated. For purification, the crude product (70 mg) was chromatographed on silica gel using a 98:2 mixture of methylene chloride and methanol as the eluent. There were obtained 52 mg (77% of theory) of tert-butyl (3RS,4RS,5SR)-4-[4-(3-benzyloxy-propoxy)-phenyl]-3-(naphthalen-2-ylmethoxy)-5-[1,2,4]triazol-1-ylmethyl-piperidine-1-carboxylate as a colourless solid; MS: 663 (M+H)+.

Workup

  1. waitSubsequently, the mixture was left
  2. temperatureThe reaction mixture was heated to 100° C. for 24 hours
  3. customthe reaction mixture was evaporated under reduced pressure
  4. customthe residue was partitioned between water and methylene chloride
  5. customthe organic phase was separated
  6. dry with materialdried over sodium sulphate
  7. customevaporated
  8. customFor purification
  9. customthe crude product (70 mg) was chromatographed on silica gel using
  10. additiona 98:2 mixture of methylene chloride and methanol as the eluent

Sources & evidence

ORD record
ord-4752e4c146cc4447b8e100d64fdd8d17
Source dataset
uspto-grants-2000_11
Patent number
US06150526

Reaction notes

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