Reacción #66812

Ecuación de reacción

Ethyl 3-cyano-2-{[(1E)-(dimethylamino)methylidene]amino}-4,7-dihydrofuro[2,3-c]pyridine-6(5H)-carboxylate

3-chloro-4-fluoroaniline

→

title compound

Rendimiento 22.3%

Ethyl 4-[(3-chloro-4-fluorophenyl)amino]-5,8-dihydropyrido[4′,3′:4,5]furo[2,3-d]pyrimidine-7(6H)-carboxylate

Rendimiento 22.3%

Disolventes

acetonitrile

acetic acid

Condiciones de reacción

Tratamiento posterior

1. 1
   ConcentraciónThe mixture was then concentrated in vacuo
2. 2
   workup.ADDITIONdiluted with water
3. 3
   Extracciónextracted with ethyl acetate
4. 4
   SecadoThe organic layer was dried over sodium sulfate
5. 5
   Otrothe solvent was evaporated
6. 6
   OtroThe residue was triturated with dichloromethane
7. 7
   workup.WAITleft
8. 8
   FiltraciónThe precipitate was collected by suction filtration
9. 9
   OtroSubsequently, the solid was triturated with methanol
10. 10
    FiltraciónThe crystals were collected by suction filtration
11. 11
    Lavadowashed with diethyl ether

Procedimiento

Ethyl 3-cyano-2-{[(1E)-(dimethylamino)methylidene]amino}-4,7-dihydrofuro[2,3-c]pyridine-6(5H)-carboxylate from Example 37A (1.20 g, 4.14 mmol) and 3-chloro-4-fluoroaniline (1.20 g, 8.27 mmol) were heated in a mixture of acetonitrile (20 mL) and acetic acid (10 mL) in a microwave oven for 30 min to 160° C. The mixture was then concentrated in vacuo, diluted with water, basified with aqueous sodium hydroxide solution and extracted with ethyl acetate. The organic layer was dried over sodium sulfate, and the solvent was evaporated. The residue was triturated with dichloromethane and left to stand for 20 h. The precipitate was collected by suction filtration. Subsequently, the solid was triturated with methanol. The crystals were collected by suction filtration and washed with diethyl ether to yield 360 mg (22%) of the title compound. A second batch of 159 mg (10%) was obtained from the mother liquor after purification by preparative HPLC.

Fuente