Diisopropylethylamine → ethyl 1-(5-bromo-4-(4-cyclopropylnaphthalen-1-yl)-4H-1,2,4-triazol-3-ylthio)cyclobutanecarboxylate

HRID 1921713Notes

Reaction equation

HRID 1921713 reaction equation
[Br:1][C:2]1[N:3]([C:8]2[C:17]3[C:12](=[CH:13][CH:14]=[CH:15][CH:16]=3)[C:11]([CH:18]3[CH2:20][CH2:19]3)=[CH:10][CH:9]=2)[C:4]([SH:7])=[N:5][N:6]=1.Br[C:22]1([C:26]([O:28][CH2:29][CH3:30])=[O:27])[CH2:25][CH2:24][CH2:23]1.C(N(C(C)C)CC)(C)C>CN(C=O)C>[Br:1][C:2]1[N:3]([C:8]2[C:17]3[C:12](=[CH:13][CH:14]=[CH:15][CH:16]=3)[C:11]([CH:18]3[CH2:20][CH2:19]3)=[CH:10][CH:9]=2)[C:4]([S:7][C:22]2([C:26]([O:28][CH2:29][CH3:30])=[O:27])[CH2:25][CH2:24][CH2:23]2)=[N:5][N:6]=1

Participants

5

Reactant 3

HCID 81531DiisopropylethylamineHCID 97595Ethyl 1-bromocyclobutanecarboxylateHCID 178527930HCID 178527930, compound

Product 1

HCID 57811367ethyl 1-(5-bromo-4-(4-cyclopropylnaphthalen-1-yl)-4H-1,2,4-triazol-3-ylthio)cyclobutanecarboxylateYield 55%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

A solution of 5-bromo-4-(4-cyclopropylnaphthalen-1-yl)-4H-1,2,4-triazole-3-thiol (100 mg, 0.289 mmol), ethyl 1-bromocyclobutanecarboxylate (47 μL, 0.289 mmol) and diisopropylethylamine (151 μL, 0.866 mmol) in DMF (1 mL) was heated at 60° C. for 4 days. After cooling to room temperature, the mixture was concentrated and partitioned between dichloromethane (15 mL) and HCl (1N aqueous, 15 mL). The aqueous layer was extracted with dichloromethane (2×15 mL) and the combined organic extracts dried over sodium sulfate, concentrated and purified by column chromatography (40% EtOAc/hexanes) to provide ethyl 1-(5-bromo-4-(4-cyclopropylnaphthalen-1-yl)-4H-1,2,4-triazol-3-ylthio)cyclobutanecarboxylate as a light yellow sticky foam (75 mg, 55% yield).

Workup

  1. concentrationthe mixture was concentrated
  2. custompartitioned between dichloromethane (15 mL) and HCl (1N aqueous, 15 mL)
  3. extractionThe aqueous layer was extracted with dichloromethane (2×15 mL)
  4. dry with materialthe combined organic extracts dried over sodium sulfate
  5. concentrationconcentrated
  6. custompurified by column chromatography (40% EtOAc/hexanes)

Sources & evidence

ORD record
ord-091a66f0d1564825ad9ecc828fe07b15
Source dataset
uspto-grants-2012_05
Patent number
US08173690B2

Reaction notes

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