تفاعل #461291

معادلة التفاعل

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

n-butyllithium

1H-indazole-3-carboxylic acid

→

title compound

المردود 67.5%

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

المردود 67.5%

المذيبات

tetrahydrofuran

hexane

N,N-dimethylformamide

ظروف التفاعل

المعالجة

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

الإجراء التجريبي

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).

المصدر