Propionyl chloride → (S)-5-[3-(5-ethyl-1,2,4-oxadiazol-3-yl)phenyl]-9-methylthio-1,2,3,3a,4,5-hexahydro-5,8,10,10b-tetraazabenzo[e]azulen-6-one

HRID 1672792Notes

Reaction equation

HRID 1672792 reaction equation
[C:1]([C:3]1[CH:4]=[C:5]([N:9]2[CH2:18][C@H:17]3[N:13]([CH2:14][CH2:15][CH2:16]3)[C:12]3[N:19]=[C:20]([S:23][CH3:24])[N:21]=[CH:22][C:11]=3[C:10]2=[O:25])[CH:6]=[CH:7][CH:8]=1)#[N:2].Cl.[NH2:27][OH:28].[CH:29](N(CC)C(C)C)([CH3:31])[CH3:30].C(Cl)(=O)CC>C(O)C.C(OCC)(=O)C>[CH2:29]([C:31]1[O:28][N:27]=[C:1]([C:3]2[CH:4]=[C:5]([N:9]3[CH2:18][C@H:17]4[N:13]([CH2:14][CH2:15][CH2:16]4)[C:12]4[N:19]=[C:20]([S:23][CH3:24])[N:21]=[CH:22][C:11]=4[C:10]3=[O:25])[CH:6]=[CH:7][CH:8]=2)[N:2]=1)[CH3:30]

Participants

7

Reactant 4

HCID 62324Propionyl chlorideHCID 81531DiisopropylethylamineHCID 443297Hydroxyamine hydrochlorideHCID 67351154(S)-5-(3-Cyanophenyl)-9-methylthio-1,2,3,3a,4,5-hexahydro-5,8,10,10b-tetraazabenzo[e]azulen-6-one

Product 1

HCID 67352878(S)-5-[3-(5-ethyl-1,2,4-oxadiazol-3-yl)phenyl]-9-methylthio-1,2,3,3a,4,5-hexahydro-5,8,10,10b-tetraazabenzo[e]azulen-6-oneYield 70%

Reagents, catalysts & solvents 2

HCID 702EthanolSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
70 °C

Procedure

(S)-5-(3-Cyanophenyl)-9-methylthio-1,2,3,3a,4,5-hexahydro-5,8,10,10b-tetraazabenzo[e]azulen-6-one (300 mg, 0.854 mmol) obtained in Step 1 was dissolved in ethanol (10 mL), and the mixture was stirred at 70° C. for 3 hours after adding hydroxylamine hydrochloride (65.0 mg, 0.939 mmol) and N,N-diisopropylethylamine (0.164 mL, 0.939 mmol). The mixture was concentrated, diluted with chloroform, and washed with water and saturated brine. The organic layer was dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The resulting residue was dissolved in pyridine (4 mL), and stirred therein at 90° C. for 5 hours after adding propionyl chloride (0.103 mL, 1.19 mmol). The mixture was cooled to room temperature, and diluted with ethyl acetate. The organic layer was washed with 1 mol/L hydrochloric acid and saturated brine, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The resulting residue was then purified by silica gel column chromatography to give (S)-5-[3-(5-ethyl-1,2,4-oxadiazol-3-yl)phenyl]-9-methylthio-1,2,3,3a,4,5-hexahydro-5,8,10,10b-tetraazabenzo[e]azulen-6-one (252 mg, 70%).

Workup

  1. concentrationThe mixture was concentrated
  2. additiondiluted with chloroform
  3. washwashed with water and saturated brine
  4. dry with materialThe organic layer was dried over anhydrous magnesium sulfate
  5. concentrationconcentrated under reduced pressure
  6. dissolutionThe resulting residue was dissolved in pyridine (4 mL)
  7. stirringstirred
  8. temperatureThe mixture was cooled to room temperature
  9. washThe organic layer was washed with 1 mol/L hydrochloric acid and saturated brine
  10. dry with materialdried over anhydrous magnesium sulfate
  11. concentrationconcentrated under reduced pressure
  12. customThe resulting residue was then purified by silica gel column chromatography

Sources & evidence

ORD record
ord-9cce2cbdf4224e7890f3f15971ae6a3b
Source dataset
uspto-grants-2011_08
Patent number
US07998954B2

Reaction notes

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