Acetyl chloride → HCID 178432614, compound

HRID 966154Notes

Reaction equation

HRID 966154 reaction equation
[C:1]([C:3]1[C:4]([CH:13]([CH3:15])[CH3:14])=[C:5]2[N:10]([CH:11]=1)[N:9]=[CH:8][NH:7][C:6]2=[O:12])#[N:2].C(=O)([O-])[O-].[K+].[K+].Cl.[NH2:23]O.[C:25](Cl)(=[O:27])[CH3:26]>C(O)C.N1C=CC=CC=1.C(OCC)(=O)C.O>[CH3:14][CH:13]([C:4]1[C:3]([C:1]2[N:23]=[C:25]([CH3:26])[O:27][N:2]=2)=[CH:11][N:10]2[C:5]=1[C:6]([OH:12])=[N:7][CH:8]=[N:9]2)[CH3:15]

Participants

9

Reactant 4

HCID 6367Acetyl chlorideHCID 11430Potassium CarbonateHCID 443297Hydroxyamine hydrochloride2×HCID 1354619136-cyano-5-(1-methylethyl)pyrrolo[2,1-f][1,2,4]triazin-4(3H)-one2×

Product 1

HCID 178432614HCID 178432614, compoundYield 11%

Reagents, catalysts & solvents 4

HCID 702EthanolSolventHCID 962WaterSolventHCID 1049PyridineSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
120 °C

Procedure

To a solution of 6-cyano-5-(1-methylethyl)pyrrolo[2,1-f][1,2,4]triazin-4(3H)-one (compound B in Example 29) (70 mg, 0.35 mmol) in ethanol (4 mL) were added potassium carbonate (23 mg, 1.7 mmol) and hydroxylamine hydrochloride (73 mg, 1 mmol) and the resulting mixture was refluxed. After 15 h, more hydroxylamine hydrochloride (2 equivalent) was added. After a total of 26 h, the mixture was cooled, water was added and the mixture was extracted with ethyl acetate. The organic layer was washed with brine, dried and concentrated. The residue was purified by silica gel flash column chromatography eluting with 5% methanol in chloroform to afford a solid which was dissolved in pyridine and treated with acetyl chloride (4 equivalent). The mixture was stirred at 120° C. for 7 h, cooled to RT, dissolved in ethyl acetate and washed with water, 1 N NaOH solution and 1N HCl. The organic layer was dried, concentrated and the residue was purified by silica gel column eluting with 5% methanol in chloroform to afford 5-(1-methylethyl)-6-(5-methyl-[1,2,4]oxadiazol-3-yl)pyrrolo[2,1-f][1,2,4]triazin-4-ol (10 mg, 11% over two steps) as a white solid. LC/MS; (M+H)+=260.2.

Workup

  1. temperaturethe resulting mixture was refluxed
  2. temperatureAfter a total of 26 h, the mixture was cooled
  3. extractionthe mixture was extracted with ethyl acetate
  4. washThe organic layer was washed with brine
  5. customdried
  6. concentrationconcentrated
  7. customThe residue was purified by silica gel flash column chromatography
  8. washeluting with 5% methanol in chloroform
  9. customto afford a solid which
  10. temperaturecooled to RT
  11. washwashed with water, 1 N NaOH solution and 1N HCl
  12. customThe organic layer was dried
  13. concentrationconcentrated
  14. customthe residue was purified by silica gel column
  15. washeluting with 5% methanol in chloroform

Sources & evidence

ORD record
ord-fe065174f651451cb476a7b21f61094d
Source dataset
uspto-grants-2005_10
Patent number
US06951859B2

Reaction notes

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