Reacción #68673

Ecuación de reacción

(Z)-tert-butyl (6-(chloro(hydroxyimino)methyl)-[1,2,4]triazolo[4,3-b]pyridazin-3-yl)methylcarbamate

ethynylcyclopropane

potassium hydrogencarbonate

→

title compound

Rendimiento 23.2%

(6-(5-cyclopropylisoxazol-3-yl)-[1,2,4]-triazolo-[4,3-b]pyridazin-3-yl)methanamine

Rendimiento 23.2%

Disolventes

EtOAc

Condiciones de reacción

Tratamiento posterior

1. 1
   Otroto afford the protected intermediate
2. 2
   OtroThe solvent was removed by rotary evaporation
3. 3
   workup.DISSOLUTIONthe residue was redissolved in dicholoromethane (5 mL) and TFA (2 mL)
4. 4
   OtroThe solvent was then removed
5. 5
   workup.DISSOLUTIONthe residue was redissolved in MeOH
6. 6
   workup.ADDITIONSolid K2CO3 was added
7. 7
   workup.STIRRINGthe mixture was stirred for 1 h to free base the title compound
8. 8
   OtroPurified the amine via MPLC (DCM/MeOH+1% NH4OH)

Procedimiento

Dissolved (Z)-tert-butyl (6-(chloro(hydroxyimino)methyl)-[1,2,4]triazolo[4,3-b]pyridazin-3-yl)methylcarbamate (110 mg, 337 μmol), ethynylcyclopropane (28 μl, 337 μmol), and potassium hydrogencarbonate (67.4 mg, 673 μmol) in 0.3 mL of EtOAc and heated to 60° C. for 12 h to afford the protected intermediate. The solvent was removed by rotary evaporation and the residue was redissolved in dicholoromethane (5 mL) and TFA (2 mL) and stirred for 30 min at room temperature. The solvent was then removed and the residue was redissolved in MeOH. Solid K2CO3 was added and the mixture was stirred for 1 h to free base the title compound. Purified the amine via MPLC (DCM/MeOH+1% NH4OH) to afford the title compound (20 mg, 23% yield).

Fuente