Acetohydrazide → 8-bromo-N-(tert-butyl)-3-(5-methyl-1,3,4-oxadiazol-2-yl)quinoxalin-2-amine

HRID 1056251Notes

Reaction equation

HRID 1056251 reaction equation
[C:1]([NH:4][NH2:5])(=[O:3])[CH3:2].[Br:6][C:7]1[CH:16]=[CH:15][CH:14]=[C:13]2[C:8]=1[N:9]=[C:10]([NH:20][C:21]([CH3:24])([CH3:23])[CH3:22])[C:11]([C:17](O)=O)=[N:12]2.CCCP1(OP(CCC)(=O)OP(CCC)(=O)O1)=O>CCOC(C)=O>[Br:6][C:7]1[CH:16]=[CH:15][CH:14]=[C:13]2[C:8]=1[N:9]=[C:10]([NH:20][C:21]([CH3:23])([CH3:22])[CH3:24])[C:11]([C:17]1[O:3][C:1]([CH3:2])=[N:4][N:5]=1)=[N:12]2

Participants

5

Reactant 3

HCID 14039AcetohydrazideHCID 111923Propylphosphonic anhydrideHCID 897819945-Bromo-3-(tert-butylamino)quinoxaline-2-carboxylic acid

Product 1

HCID 897840678-bromo-N-(tert-butyl)-3-(5-methyl-1,3,4-oxadiazol-2-yl)quinoxalin-2-amineYield 46%

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent

Conditions

Temperature
90 °C

Procedure

Acetic hydrazide (33 mg, 0.44 mmol) and 5-bromo-3-(tert-butylamino)quinoxaline-2-carboxylic acid (371a) (130 mg, 0.40 mmol) were combined in EtOAc (4 mL) to give a yellow solution. TEA (0.17 mL, 1.20 mmol) was added followed by 1-propanephosphonic acid cyclic anhydride (Aldrich; 50 wt. % solution in EtOAc, 0.59 mL, 1.00 mmol). The reaction was sealed and heated in an oil bath at 90° C. for 16 h. The reaction mixture was cooled to RT, partitioned between saturated NaHCO3 and EtOAc. The aq. layer was extracted with EtOAc and the combined organic layers were washed with brine, and the organic layer was dried over anhydrous Na2SO4, filtered, and concentrated in vacuo. The residue was adsorbed onto 1 g silica gel and purified by silica gel chromatography (12 g column) using a gradient of 0-20% EtOAc/hexanes to afford 8-bromo-N-(tert-butyl)-3-(5-methyl-1,3,4-oxadiazol-2-yl)quinoxalin-2-amine (67 mg, 0.18 mmol, 46% yield) as a yellow solid. m/z (ESI, +ve ion) 362.0/364.0 (M+H)+.

Workup

  1. customto give a yellow solution
  2. customThe reaction was sealed
  3. temperatureThe reaction mixture was cooled to RT
  4. custompartitioned between saturated NaHCO3 and EtOAc
  5. extractionThe aq. layer was extracted with EtOAc
  6. washthe combined organic layers were washed with brine
  7. dry with materialthe organic layer was dried over anhydrous Na2SO4
  8. filtrationfiltered
  9. concentrationconcentrated in vacuo
  10. custompurified by silica gel chromatography (12 g column)

Sources & evidence

ORD record
ord-92af456e3be44eac8facbc14c43744ea
Source dataset
uspto-grants-2016_07
Patent number
US09394297B2

Reaction notes

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