Réaction #5668

Équation de réaction

2,3-Dihydro-7-methoxy-1,4-benzodioxin-2-methanamine hydrochloride

7-(3-bromopropoxy)chromen-4-one

diisopropylethylamine

→

title compound

Rendement 4.4%

7-[3-[(7-Methoxy-2,3-dihydro-benzo[1,4]dioxin-2-ylmethyl)amino]propoxy]chromen-4-one

Rendement 4.4%

Solvants

DMF

Conditions de réaction

Traitement

1. 1
   AutreThe solvent was then removed
2. 2
   LavageThe mixture was washed with an equal volume of saturated aqueous sodium bicarbonate, with saturated aqueous sodium chloride
3. 3
   Séchagedried over anhydrous magnesium sulfate
4. 4
   Filtrationfiltered
5. 5
   Concentrationconcentrated in vacuum
6. 6
   AutreThe residue was chromatographed on a silica gel column
7. 7
   workup.ADDITIONThe fractions containing material with Rf=0.59 on silica gel tlc (chloroform/methanol/ammonia=95/5/1)
8. 8
   Concentrationconcentrated
9. 9
   workup.DISSOLUTIONthe residue was dissolved in 50% methanol/dichloromethane
10. 10
    workup.ADDITIONThe mixture was then treated with 4N isopropanolic HCl until the solution
11. 11
    Autrecrystallized
12. 12
    Autreby triturating with ether
13. 13
    AutreTwo further recrystallizations

Mode opératoire

2,3-Dihydro-7-methoxy-1,4-benzodioxin-2-methanamine hydrochloride (4.0 g, 17 mmole), 7-(3-bromopropoxy)chromen-4-one (4.9 g, 17 mmole) and diisopropylethylamine (15.1 ml, 87 mmole) were combined in 150 ml of DMF and heated at 80° C. for 24 hours under a nitrogen atmosphere. The solvent was then removed and replaced with dichloromethane. The mixture was washed with an equal volume of saturated aqueous sodium bicarbonate, with saturated aqueous sodium chloride, dried over anhydrous magnesium sulfate, filtered, and concentrated in vacuum. The residue was chromatographed on a silica gel column using first dichloromethane and then 5% methanolic dichloromethane as eluents. The fractions containing material with Rf=0.59 on silica gel tlc (chloroform/methanol/ammonia=95/5/1) were combined, concentrated, and the residue was dissolved in 50% methanol/dichloromethane. The mixture was then treated with 4N isopropanolic HCl until the solution was 3 in pH and crystallized by triturating with ether. Two further recrystallizations gave 0.3 g of title compound as a yellow solid hydrochloride, quarter hydrate, m.p. 155°-157° C.

Source