Triethylamine → HCID 66618388, compound

HRID 1696814Notes

Reaction equation

HRID 1696814 reaction equation
[OH:1][NH:2][C:3](=[NH:11])[C:4]1[CH:9]=[CH:8][C:7]([F:10])=[CH:6][CH:5]=1.[C:12]([O:16][C:17]([N:19]1[CH2:24][CH2:23][N:22]([CH3:25])[CH:21]([C:26](O)=O)[CH2:20]1)=[O:18])([CH3:15])([CH3:14])[CH3:13].CCN=C=NCCCN(C)C.Cl.C1C=CC2N(O)N=NC=2C=1.C(N(CC)CC)C>O1CCOCC1>[C:12]([O:16][C:17]([N:19]1[CH2:24][CH2:23][N:22]([CH3:25])[CH:21]([C:26]2[O:1][N:2]=[C:3]([C:4]3[CH:5]=[CH:6][C:7]([F:10])=[CH:8][CH:9]=3)[N:11]=2)[CH2:20]1)=[O:18])([CH3:15])([CH3:14])[CH3:13]

Participants

7

Reactant 5

HCID 8471TriethylamineHCID 757711-HydroxybenzotriazoleHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 600810424-((Tert-butoxy)carbonyl)-1-methylpiperazine-2-carboxylic acidHCID 178513323HCID 178513323, compound

Product 1

HCID 66618388HCID 66618388, compoundYield 17.5%

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent

Procedure

A mixture of N-hydroxy-4-fluoro-benzamidine (0.758 g, 4.92 mmol), 4-methyl-piperazine-1,3-dicarboxylic acid 1-tert-butyl ester (4.92 mmol), prepared as described in 62(B), EDCI.HCl (1.41 g, 7.38 mmol), HOBT (0.665 g, 4.92 mmol) and anhydrous triethylamine (1.38 mL, 9.84 mmol) in dioxane (80 mL) was stirred at room temperature for a week-end, under nitrogen atmosphere. Then, the reaction mixture was refluxed for 7 h and the solvent was evaporated under reduced pressure. The residue was diluted with water (50 mL) and ethyl acetate (50 mL), the phases were separated and the organic layer was washed sequentially with water (50 mL×2 times) and with NaOH 1N (50 mL×2 times). The organic layer was dried over Na2SO4 and concentrated under reduced pressure to give a yellow oil. Purification of the crude by flash chromatography (silica gel, eluent gradient: from hexane/ethyl acetate 8/2 to hexane/ethyl acetate 7/3) afforded 0.312 g of 3-[3-(4-fluoro-phenyl)-[1,2,4]oxadiazol-5-yl]-4-methyl-piperazine-1-carboxylic acid tert-butyl ester as a yellow oil.

Workup

  1. customprepared
  2. temperatureThen, the reaction mixture was refluxed for 7 h
  3. customthe solvent was evaporated under reduced pressure
  4. additionThe residue was diluted with water (50 mL) and ethyl acetate (50 mL)
  5. customthe phases were separated
  6. washthe organic layer was washed sequentially with water (50 mL×2 times) and with NaOH 1N (50 mL×2 times)
  7. dry with materialThe organic layer was dried over Na2SO4
  8. concentrationconcentrated under reduced pressure
  9. customto give a yellow oil
  10. customPurification of the crude by flash chromatography (silica gel, eluent gradient: from hexane/ethyl acetate 8/2 to hexane/ethyl acetate 7/3)

Sources & evidence

ORD record
ord-4a3555bb8fe94224a80c476dada5b10c
Source dataset
uspto-grants-2012_04
Patent number
US08163775B2

Reaction notes

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