Nitrogen → 6-Amino-5-(4-fluorobenzoyl)-1-(4-oxo-cyclohexyl)-1H-pyridin-2-one

HRID 1667365Notes

Reaction equation

HRID 1667365 reaction equation
[C:1]([O-:4])([O-])=O.[K+].[K+].[O:7]1[C:11]2([CH2:16][CH2:15][CH:14]([NH:17][C:18](=S)[CH2:19][C:20]([C:22]3[CH:27]=[CH:26][C:25]([F:28])=[CH:24][CH:23]=3)=[O:21])[CH2:13][CH2:12]2)OCC1.[N:30]#N.[CH2:32](I)[CH3:33]>CC(C)=O.CCOC(C)=O>[NH2:30][C:18]1[N:17]([CH:14]2[CH2:13][CH2:12][C:11](=[O:7])[CH2:16][CH2:15]2)[C:1](=[O:4])[CH:33]=[CH:32][C:19]=1[C:20](=[O:21])[C:22]1[CH:23]=[CH:24][C:25]([F:28])=[CH:26][CH:27]=1

Participants

7

Reactant 4

HCID 947Nitrogen2×HCID 6340IodoethaneHCID 11430Potassium CarbonateHCID 57658315N-(1,4-Dioxaspiro[4.5]dec-8-yl)-3-(4-fluorophenyl)-3-oxo-thiopropionamide

Product 1

HCID 576584256-Amino-5-(4-fluorobenzoyl)-1-(4-oxo-cyclohexyl)-1H-pyridin-2-one

Reagents, catalysts & solvents 2

HCID 180AcetoneSolventHCID 8857Ethyl AcetateSolvent

Procedure

K2CO3 (16.1 g, 117 mmol) was added to a solution of N-(1,4-Dioxaspiro[4.5]dec-8-yl)-3-(4-fluorophenyl)-3-oxo-thiopropionamide (18.8 g, 55.7 mmol) in acetone (200 ml) at RT/N2 followed by the ethyl iodide (6.68 ml, 83.6 mmol). The reaction mixture was stirred at RT/N2 for 2 h and then concentrated in vacuo giving a brown paste which was taken up in EtOAc (300 ml) and washed with H2O (250 ml). The organic phase was separated and the aqueous phase was extracted with EtOAc (2×150 ml). The combined organic phases were dried (Na2SO4), filtered and concentrated in vacuo a brown oil. Purification by flash column chromatography (silica, 15% EtOAc/Heptane) gave a yellow oil. Yield=9.94 g, 49%. LCMS purity 94%, m/z 366 [M+H]+.

Workup

  1. concentrationconcentrated in vacuo
  2. customgiving a brown paste which
  3. washwashed with H2O (250 ml)
  4. customThe organic phase was separated
  5. extractionthe aqueous phase was extracted with EtOAc (2×150 ml)
  6. dry with materialThe combined organic phases were dried (Na2SO4)
  7. filtrationfiltered
  8. concentrationconcentrated in vacuo a brown oil
  9. customPurification by flash column chromatography (silica, 15% EtOAc/Heptane)
  10. customgave a yellow oil

Sources & evidence

ORD record
ord-8a90fd7b82d841839d68bab56aaf07b8
Source dataset
uspto-grants-2011_10
Patent number
US08044211B2

Reaction notes

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