Reacción #6927

Ecuación de reacción

(4-benzyloxyphenyl)-(6-iodo-7-fluoro-quinazolin-4-yl)-amine hydrochloride

5-(1,3-dioxolan-2-yl)-2-(tributylstannyl)furan

diisopropylethyl amine

→

solid

Rendimiento 59.4%

(4-Benzyloxyphenyl)-(6-(5-(1,3-dioxolan-2-yl)-furan-2-yl)-7-fluoro-quinazolin-4-yl)-amine

Rendimiento 59.4%

Disolventes

DMF

Condiciones de reacción

Tratamiento posterior

1. 1
   OtroSynthesized
2. 2
   OtroThe cooled reaction mixture
3. 3
   Extracciónwas extracted with water (100 ml) and ethyl acetate (100 ml)
4. 4
   LavadoThe organic phase was washed with brine (100 ml)
5. 5
   Lavadowashed with additional ethyl acetate (100 ml)
6. 6
   Secadodried with MgSO4
7. 7
   Filtraciónfiltered
8. 8
   Concentraciónconcentrated to a residue
9. 9
   OtroThe residue was chromatographed on silica gel with a methanol-chloroform mixture
10. 10
    OtroFractions were collected
11. 11
    Concentraciónconcentrated
12. 12
    workup.ADDITIONdiethyl ether was added
13. 13
    Otroprecipitation
14. 14
    FiltraciónThe solid was filtered
15. 15
    Otrodried under vacuum at room temperature

Procedimiento

Synthesized according to Procedure B from a solution of (4-benzyloxyphenyl)-(6-iodo-7-fluoro-quinazolin-4-yl)-amine hydrochloride (508 mg, 1 mmole), 5-(1,3-dioxolan-2-yl)-2-(tributylstannyl)furan (645 mg, 1.5 mmole), diisopropylethyl amine (650 mg, 5 mmole), and dichlorobis(triphenylphosphine) palladium (140 mg, 0.2 mmole) in 6 ml of DMF under nitrogen was stirred at 100° C. (oil bath temperature) for 4 hours. The cooled reaction mixture was extracted with water (100 ml) and ethyl acetate (100 ml). The organic phase was washed with brine (100 ml). The aqueous layers were combined and washed with additional ethyl acetate (100 ml). The organic layers were combined, dried with MgSO4, filtered and concentrated to a residue. The residue was chromatographed on silica gel with a methanol-chloroform mixture. Fractions were collected, combined, and concentrated. The resultant solid was suspended in dichloromethane (10 ml) and diethyl ether was added facilitate precipitation. The solid was filtered and dried under vacuum at room temperature to yield a yellowish solid 287 mg (59%). 1H NMR (400 MHz, DMSO-d6) δ: 10.1(s, 1H), 8.85(d, 1H), 8.45(s, 1H), 7.6(m, 3H), 7.44(d, 2H), 7.38(m, 2H), 7.31(m, 1H), 7.03(m, 2H), 6.94(m, 1H), 6.74(d, 1H), 6.01(s, 1H), 5.1(s, 2H), 4.10(m, 2H), 3.96(m, 2H). ESI-MS m/z 482(M−1).

Fuente