Reaktion #6927

Reaktionsgleichung

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

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

diisopropylethyl amine

→

solid

Ausbeute 59.4%

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

Ausbeute 59.4%

Lösungsmittel

DMF

Reaktionsbedingungen

Aufarbeitung

1. 1
   SonstigeSynthesized
2. 2
   SonstigeThe cooled reaction mixture
3. 3
   Extraktionwas extracted with water (100 ml) and ethyl acetate (100 ml)
4. 4
   WaschenThe organic phase was washed with brine (100 ml)
5. 5
   Waschenwashed with additional ethyl acetate (100 ml)
6. 6
   Trocknendried with MgSO4
7. 7
   Filtrationfiltered
8. 8
   Einengenconcentrated to a residue
9. 9
   SonstigeThe residue was chromatographed on silica gel with a methanol-chloroform mixture
10. 10
    SonstigeFractions were collected
11. 11
    Einengenconcentrated
12. 12
    workup.ADDITIONdiethyl ether was added
13. 13
    Sonstigeprecipitation
14. 14
    FiltrationThe solid was filtered
15. 15
    Sonstigedried under vacuum at room temperature

Vorschrift

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).

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