Reaktion #452568

Reaktionsgleichung

3,N-(N,N-Dimethylaminopropyl)-1,N-ethylcarbodiimide hydrochloride

EDAC.HCl

6-amino-4-(4-benzyloxyanilino)quinazoline

acrylic acid

pyridine

Na2CO3

→

N-(4-[4-benzyloxyanilino]-quinazolin-6-yl)acrylamide

Ausbeute 38.3%

Lösungsmittel

THF

water

MeOH CHCl3

Reaktionsbedingungen

Aufarbeitung

1. 1
   workup.STIRRINGso the reaction mixture was stirred at 25° C. for 2 hours
2. 2
   Sonstigewas recooled to 0° C.
3. 3
   Filtrationcollected by Buchner filtration
4. 4
   Waschenrinsed with water (2×10 mL)
5. 5
   Sonstigedried in a vacuum oven at 65° C. for 4 hours
6. 6
   TemperaturThe pumpkin organge solid was refluxed
7. 7
   Sonstigesonicated in CHCl3 -acetone (1:1,40 mL)
8. 8
   workup.ADDITIONcontaining silica gel (5 g)
9. 9
   SonstigeThe volatiles were removed under reduced pressure
10. 10
    Wascheneluting with 25% acetone/CHCl3
11. 11
    SonstigeRemoval of the solvent under reduced pressure

Vorschrift

3,N-(N,N-Dimethylaminopropyl)-1,N-ethylcarbodiimide hydrochloride (EDAC.HCl) (385 mg, 2.0 mmol) was added in one portion to a solution of 6-amino-4-(4-benzyloxyanilino)quinazoline (342 mg, 1.0 mmol), acrylic acid (144 mg, 2.0 mmol), and pyridine (163 mg, 2.06 mmol) in THF (10 mL) stirred under nitrogen at 0° C. After 4 hours at 0° C., tlc (10% MeOH/CHCl3) showed considerable SM, so the reaction mixture was stirred at 25° C. for 2 hours. The mixture was recooled to 0° C., and water (2 mL) was added dropwise. This solution was poured onto rapidly stirred ice-water (40 mL), the pH was raised to 7 with saturated Na2CO3 solution, and the very fine ppt was allowed to settle, collected by Buchner filtration, rinsed with water (2×10 mL), and dried in a vacuum oven at 65° C. for 4 hours. The pumpkin organge solid was refluxed and sonicated in CHCl3 -acetone (1:1,40 mL), containing silica gel (5 g). The volatiles were removed under reduced pressure and the residual solid was used as the origin of a silica gel flash chromatography column, eluting with 25% acetone/CHCl3. Removal of the solvent under reduced pressure gave N-(4-[4-benzyloxyanilino]-quinazolin-6-yl)acrylamide (152 mg, 38%) as a bright yellow glass; mp 227-229° C. Calculated for C24H20N4O2C20H16N4O.0.1 HCl: C, 72.04; H, 5.06; N, 14.01%. Found: C, 71.80; H, 4.93: N, 13.80%. 1H NMR (DMSO-d6): δ10.47 (1 H, sl brs), 9.74 (1 H, sl brs), 8.76 (1 H, d, J=1.9 Hz), 8.45 (1 H, s), 7.86 (1 H, dd, J=2.0, 9.0 Hz), 7.74 (1 H, d, J=8.9 Hz), 7.66 (2 H, d, J=9.2 Hz), 7.49 (2 H, t, J=7.2 Hz), 7.41 (2 H, t, J=7.4 Hz), 7.34 (1 H, t, J=7.2 Hz), 7.04 (2 H, d, J=9.2 Hz), 6.53 (1 H, dd, J=10.1, 16.9 Hz), 6.34 (1 H, dd, J=1.9, 16.9 Hz), 5.83 (1 H, dd, J=1.9, 10.1 Hz), 5.13 (2 H, s). Mass spectrum (APCI) 397.2 (100 MH+).

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