Réaction #2461603

Équation de réaction

Sodium hexamethyldisilazane

4-amino-5-chloro-2,3-methylenedioxypyridine

4-chloro-7-(3-chloropropoxy)-6-methoxyquinazoline

→

title compound

Rendement 74.6%

4-(5-chloro-2,3-methylenedioxypyrid-4-ylamino)-7-(3-chloropropoxy)-6-methoxyquinazoline

Rendement 74.6%

Solvants

DMF

Conditions de réaction

Traitement

1. 1
   Températureto warm to ambient temperature
2. 2
   workup.STIRRINGThe mixture was stirred at ambient temperature for 16 hours
3. 3
   AutreThe reaction mixture was evaporated
4. 4
   Autrethe residue was partitioned between methylene chloride
5. 5
   LavageThe organic phase was washed with water and with brine
6. 6
   Séchagedried over magnesium sulphate
7. 7
   Autreevaporated
8. 8
   AutreThe residue was purified by column chromatography on silica using
9. 9
   Températureincreasingly polar mixtures of methylene chloride and ethyl acetate as eluent
10. 10
    Températureby increasingly polar mixtures of methylene chloride and acetonitrile

Mode opératoire

Sodium hexamethyldisilazane (1M solution in THF; 0.734 ml) was added to a solution of 4-amino-5-chloro-2,3-methylenedioxypyridine (0.12 g) in DMF (4 ml) that had been cooled to 0° C. and the mixture was stirred for 15 minutes. A portion (0.1 g) of 4-chloro-7-(3-chloropropoxy)-6-methoxyquinazoline was added and the resultant mixture was stirred and allowed to warm to ambient temperature. The mixture was stirred at ambient temperature for 16 hours. The reaction mixture was evaporated and the residue was partitioned between methylene chloride and a saturated aqueous ammonium chloride solution. The organic phase was washed with water and with brine, dried over magnesium sulphate and evaporated. The residue was purified by column chromatography on silica using increasingly polar mixtures of methylene chloride and ethyl acetate as eluent followed by increasingly polar mixtures of methylene chloride and acetonitrile. There was thus obtained the title compound as a white foam (0.11 g); NMR Spectrum: (DMSOd6 and CD3CO2D) 2.3 (m, 2H), 3.8 (m, 2H), 4.05 (s, 3H), 4.4 (t, 2H), 6.3 (s, 2H), 7.4 (s, 1H), 7.9 (s, 1H), 8.15 (s, 1H), 8.95 (s, 1H); Mass Spectrum: M+H+ 423 and 425.

Source