Reaktion #461291

Reaktionsgleichung

1,4-dimethy-6-hydroxyhexahydro-1H-1,4-diazepine

n-butyllithium

1H-indazole-3-carboxylic acid

→

title compound

Ausbeute 67.5%

(1,4-dimethylhexahydro-1H-1,4-diazepin-6-yl) 1H-indazole-3-carboxylate

Ausbeute 67.5%

Lösungsmittel

tetrahydrofuran

hexane

N,N-dimethylformamide

Reaktionsbedingungen

Aufarbeitung

1. 1
   workup.ADDITIONTo the reaction mixture is added dropwise
2. 2
   Sonstigethe reaction mixture prepared by the following method
3. 3
   Temperaturcooled to 25° C
4. 4
   SonstigeThe resulting reaction mixture
5. 5
   Temperaturis refluxed
6. 6
   workup.STIRRINGwith stirring for 1 hour
7. 7
   SonstigeTetrahydrofuran is evaporated under reduced pressure
8. 8
   workup.ADDITIONthe residue is diluted with water
9. 9
   Extraktionextracted with diethyl ether
10. 10
    WaschenThe organic layer is washed with saturated sodium chloride solution
11. 11
    Trocknendried over magnesium sulfate
12. 12
    SonstigeThe solvent is evaporated under reduced pressure
13. 13
    Sonstigethe residue is chromatographed on silica gel with elution of chloroform-methanol ( 9:1)
14. 14
    workup.ADDITIONFractions containing the title compound
15. 15
    Sonstigeevaporated under reduced pressure

Vorschrift

To a solution of 1,4-dimethy-6-hydroxyhexahydro-1H-1,4-diazepine (1.9 g) in anhydrous tetrahydrofuran (10 ml), a solution of n-butyllithium in hexane (9.4 g) is added dropwise under nitrogen stream at 25° C., and the mixture is stirred for 30 minutes at the same temperature. To the reaction mixture is added dropwise, the reaction mixture prepared by the following method; to a solution of 1H-indazole-3-carboxylic acid (2.0 g) in anhydrous N,N-dimethylformamide (20 ml), N,N'-carbonyldiimidazole (2.0 g) is added at 25° C., and the mixture is heated at 80° C. for 4.5 hours and cooled to 25° C. The resulting reaction mixture is refluxed with stirring for 1 hour. Tetrahydrofuran is evaporated under reduced pressure, and the residue is diluted with water, extracted with diethyl ether. The organic layer is washed with saturated sodium chloride solution and dried over magnesium sulfate. The solvent is evaporated under reduced pressure, and the residue is chromatographed on silica gel with elution of chloroform-methanol ( 9:1). Fractions containing the title compound are pooled and evaporated under reduced pressure to give the title compound (2.4 g) as an oil. The free base is converted to 5/2 fumarate 1/4 ethanol of the title compound in a usual manner, m.p. 184°-185° C. (recrystallized from ethanol).

Quelle