반응 #6927

반응 방정식

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

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

diisopropylethyl amine

→

solid

수율 59.4%

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

수율 59.4%

용매

DMF

반응 조건

후처리

1. 1
   기타Synthesized
2. 2
   기타The cooled reaction mixture
3. 3
   추출was extracted with water (100 ml) and ethyl acetate (100 ml)
4. 4
   세척The organic phase was washed with brine (100 ml)
5. 5
   세척washed with additional ethyl acetate (100 ml)
6. 6
   건조dried with MgSO4
7. 7
   여과filtered
8. 8
   농축concentrated to a residue
9. 9
   기타The residue was chromatographed on silica gel with a methanol-chloroform mixture
10. 10
    기타Fractions were collected
11. 11
    농축concentrated
12. 12
    workup.ADDITIONdiethyl ether was added
13. 13
    기타precipitation
14. 14
    여과The solid was filtered
15. 15
    기타dried under vacuum at room temperature

실험 절차

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).

출처