Diethyl Ether → N-(2-Cyclohexyl-1,5-dimethyl-3-oxo-2,3-dihydro-1H-pyrazol-4-yl)-5-(1-hydroxybut-3-en-1-yl)-4-methylisoxazole-3-carboxamide

HRID 1478189Notes

Reaction equation

HRID 1478189 reaction equation
[CH:1]1([N:7]2[C:11](=[O:12])[C:10]([NH:13][C:14]([C:16]3[C:20]([CH3:21])=[C:19]([CH:22]=[O:23])[O:18][N:17]=3)=[O:15])=[C:9]([CH3:24])[N:8]2[CH3:25])[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1.[CH2:26]([Mg]Br)[CH:27]=[CH2:28].CCOCC.[NH4+].[Cl-]>C1COCC1>[CH:1]1([N:7]2[C:11](=[O:12])[C:10]([NH:13][C:14]([C:16]3[C:20]([CH3:21])=[C:19]([CH:22]([OH:23])[CH2:28][CH:27]=[CH2:26])[O:18][N:17]=3)=[O:15])=[C:9]([CH3:24])[N:8]2[CH3:25])[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6]1

Participants

6

Reactant 4

HCID 3283Diethyl EtherHCID 25517Ammonium ChlorideHCID 118511079N-(2-Cyclohexyl-1,5-dimethyl-3-oxo-2,3-dihydro-1H-pyrazol-4-yl)-5-formyl-4-methylisoxazole-3-carboxamideHCID 178455850HCID 178455850, compound

Product 1

HCID 118511173N-(2-Cyclohexyl-1,5-dimethyl-3-oxo-2,3-dihydro-1H-pyrazol-4-yl)-5-(1-hydroxybut-3-en-1-yl)-4-methylisoxazole-3-carboxamide

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

A solution of N-(2-cyclohexyl-1,5-dimethyl-3-oxo-2,3-dihydro-1H-pyrazol-4-yl)-5-formyl-4-methylisoxazole-3-carboxamide (53 mg, 0.153 mmol) in THF (1.5 mL) was cooled to 0° C. and 1M allylmagnesium bromide in Et2O (337 μl, 0.337 mmol) was added dropwise over 15 mins. The reaction mixture was warmed to room temperature and saturated NH4Cl (aq) was added. The aqueous layer was extracted with DCM (×3). The combined organic extracts were passed through a phase separating cartridge and the organic solvent was removed under reduced pressure. The crude material was adsorbed onto silica and purification by chromatography eluting with 50-100% EtOAc in iso-hexane afforded the title compound.

Workup

  1. extractionThe aqueous layer was extracted with DCM (×3)
  2. customseparating cartridge
  3. customthe organic solvent was removed under reduced pressure
  4. customThe crude material was adsorbed onto silica and purification by chromatography
  5. washeluting with 50-100% EtOAc in iso-hexane

Sources & evidence

ORD record
ord-b133b535b9db4ddb9ae20fbac2456a5a
Source dataset
uspto-grants-2016_08
Patent number
US09403810B2

Reaction notes

Loading…