تفاعل #6927

معادلة التفاعل

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

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

diisopropylethyl amine

→

solid

المردود 59.4%

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

المردود 59.4%

المذيبات

DMF

ظروف التفاعل

المعالجة

1. 1
   أخرىSynthesized
2. 2
   أخرىThe cooled reaction mixture
3. 3
   استخلاصwas extracted with water (100 ml) and ethyl acetate (100 ml)
4. 4
   غسيلThe organic phase was washed with brine (100 ml)
5. 5
   غسيلwashed with additional ethyl acetate (100 ml)
6. 6
   تجفيفdried with MgSO4
7. 7
   ترشيحfiltered
8. 8
   تركيزconcentrated to a residue
9. 9
   أخرىThe residue was chromatographed on silica gel with a methanol-chloroform mixture
10. 10
    أخرىFractions were collected
11. 11
    تركيزconcentrated
12. 12
    workup.ADDITIONdiethyl ether was added
13. 13
    أخرىprecipitation
14. 14
    ترشيحThe solid was filtered
15. 15
    أخرىdried under vacuum at room temperature

الإجراء التجريبي

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).

المصدر