Isobutyric Acid → HCID 44819972, compound

HRID 42147Notes

Reaction equation

HRID 42147 reaction equation
[OH:1][NH:2][C:3]([N:5]1[CH2:10][CH2:9][CH:8]([C:11]2[CH:12]=[CH:13][C:14]([CH2:17][O:18][C:19]3[CH:24]=[CH:23][C:22]([S:25]([CH3:28])(=[O:27])=[O:26])=[CH:21][CH:20]=3)=[N:15][CH:16]=2)[CH2:7][CH2:6]1)=[NH:4].[C:29](O)(=O)[CH:30]([CH3:32])[CH3:31].O.ON1C2C=CC=CC=2N=N1.C(N(CC)C(C)C)(C)C.Cl.CN(C)CCCN=C=NCC.C(=O)([O-])O.[Na+]>CN(C)C=O>[CH:30]([C:32]1[O:1][N:2]=[C:3]([N:5]2[CH2:10][CH2:9][CH:8]([C:11]3[CH:12]=[CH:13][C:14]([CH2:17][O:18][C:19]4[CH:20]=[CH:21][C:22]([S:25]([CH3:28])(=[O:27])=[O:26])=[CH:23][CH:24]=4)=[N:15][CH:16]=3)[CH2:7][CH2:6]2)[N:4]=1)([CH3:31])[CH3:29]

Participants

8

Reactant 6

HCID 6590Isobutyric AcidHCID 81531DiisopropylethylamineHCID 516892Sodium BicarbonateHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 27960291-Hydroxybenzotriazole hydrateHCID 178504809HCID 178504809, compound

Product 1

HCID 44819972HCID 44819972, compoundYield 53.4%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

A solution of N-hydroxy-4-[2-(4-methanesulfonylphenoxymethyl)pyridin-5-yl]piperidin-1-carboxamidine (98 mg, 0.242 mmol), isobutyric acid (22 μL, 0.242 mmol) and 1-hydroxybenzotriazole monohydrate (41 mg, 0.267 mmol) in N,N-dimethylformamide (2 mL) was cooled in an ice bath followed by the addition of N,N-diisopropylethylamine (0.14 mL, 0.800 mmol) and 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (55 mg, 0.291 mmol). The mixture was stirred at room temperature overnight, poured into saturated aqueous sodium hydrogen carbonate solution and extracted with ethyl acetate. The organic layer was dried over anhydrous sodium sulfate and concentrated under reduced pressure. A suspension of the residue in toluene (4 mL) was refluxed for 2 hours, allowed to cool to room temperature and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (hexane/ethyl acetate=1/2→1/5) to give a crystal. The crystal was recrystallized from ethyl acetate/hexane to give the title compound as a white crystal (59 mg, yield 53%).

Workup

  1. extractionextracted with ethyl acetate
  2. dry with materialThe organic layer was dried over anhydrous sodium sulfate
  3. concentrationconcentrated under reduced pressure
  4. additionA suspension of the residue in toluene (4 mL)
  5. temperaturewas refluxed for 2 hours
  6. temperatureto cool to room temperature
  7. concentrationconcentrated under reduced pressure
  8. customThe residue was purified by silica gel column chromatography (hexane/ethyl acetate=1/2→1/5)
  9. customto give a crystal
  10. customThe crystal was recrystallized from ethyl acetate/hexane

Sources & evidence

ORD record
ord-e560d3d4a2af475595187d9464a6411a
Source dataset
uspto-grants-2013_09
Patent number
US08536176B2

Reaction notes

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