反応 #6927

反応方程式

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

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

diisopropylethyl amine

→

solid

収率 59.4%

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

収率 59.4%

溶媒

DMF

反応条件

後処理

1. 1
   その他Synthesized
2. 2
   その他The cooled reaction mixture
3. 3
   抽出was extracted with water (100 ml) and ethyl acetate (100 ml)
4. 4
   洗浄The organic phase was washed with brine (100 ml)
5. 5
   洗浄washed with additional ethyl acetate (100 ml)
6. 6
   乾燥dried with MgSO4
7. 7
   ろ過filtered
8. 8
   濃縮concentrated to a residue
9. 9
   その他The residue was chromatographed on silica gel with a methanol-chloroform mixture
10. 10
    その他Fractions were collected
11. 11
    濃縮concentrated
12. 12
    workup.ADDITIONdiethyl ether was added
13. 13
    その他precipitation
14. 14
    ろ過The solid was filtered
15. 15
    その他dried under vacuum at room temperature

実験手順

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).

出典