Reaction #336832

Reaction equation

ethyl 5-bromo-2-cyclopropyl-1,6-dihydro-6-oxo-4-pyrimidine-carboxylate

product

ethyl 5-bromo-2-cyclopropyl-1,6-dihydro-6-oxo-4-pyrimidinecarboxylate

thionyl chloride

N,N-dimethylformamide

→

title product

ethyl 6-amino-5-bromo-2-cyclopropyl-4-pyrimidinecarboxylate

Conditions

Workup

1. 1
   OtherThe solvent was removed with a rotary evaporator
2. 2
   workup.DISSOLUTIONThe residue was dissolved in dichloromethane
3. 3
   Washwashed with saturated aqueous sodium bicarbonate
4. 4
   Dryingdried (Na2SO4)
5. 5
   OtherThe solvent was removed with a rotary evaporator
6. 6
   workup.DISSOLUTIONThe residue was dissolved in tetrahydrofuran (2 mL)
7. 7
   workup.ADDITIONa methanolic solution of ammonia (7 N, 2 mL) was added
8. 8
   workup.ADDITIONDichloromethane was added
9. 9
   Filtrationthe reaction mixture was filtered
10. 10
    OtherThe solvent was removed with a rotary evaporator
11. 11
    OtherThe residue was purified by MPLC (10→30% ethyl acetate in hexanes as eluant)

Procedure

To a solution of ethyl 5-bromo-2-cyclopropyl-1,6-dihydro-6-oxo-4-pyrimidine-carboxylate (i.e. the product of Step B) (1.07 g, 3.7 mmol) in N,N-dimethylformamide (15 mL) was added thionyl chloride (0.54 mL, 7.5 mmol). The reaction mixture was stirred for 2 h. The solvent was removed with a rotary evaporator. The residue was dissolved in dichloromethane, washed with saturated aqueous sodium bicarbonate and dried (Na2SO4). The solvent was removed with a rotary evaporator. The residue was dissolved in tetrahydrofuran (2 mL), and a methanolic solution of ammonia (7 N, 2 mL) was added. The reaction mixture was placed in a sealed vial and heated in a microwave reactor at 125° C. for 2 h. The reaction mixture was allowed to stand over the weekend. Dichloromethane was added and the reaction mixture was filtered. The solvent was removed with a rotary evaporator. The residue was purified by MPLC (10→30% ethyl acetate in hexanes as eluant) to afford the title product, a compound of the present invention, as a white solid (0.52 g).

Source