تفاعل #156316

معادلة التفاعل

Carbodiimide

7-methyl-4-oxo-1-(tetrahydro-2H-pyran-4-yl)-4,5-dihydro-1H-pyrazolo[4,3-c]quinoline-8-carboxylic acid

methyl 3-piperidin-4-yl-benzoate monohydrochloride

1-hydroxybenzotriazole

Carbonate

Isocyanate

→

3-(1-{[7-methyl-4-oxo-1-(tetrahydro-2H-pyran-4-yl)-4,5-dihydro-1H-pyrazolo[4,3-c]quinolin-8-yl]carbonyl}piperidin-4-yl)benzoic acid

المردود 45.0%

المذيبات

DMF

triethylamine

DMF

ظروف التفاعل

المعالجة

1. 1
   workup.STIRRINGby stirring for 2 hours
2. 2
   ترشيحThe reaction mixture was filtered
3. 3
   تركيزthe filtrate was concentrated under reduced pressure
4. 4
   workup.ADDITIONTo the obtained residue were added 0.5 mL of methanol, 0.5 mL of tetrahydrofuran, and 0.5 mL of a 1 M aqueous sodium hydroxide solution
5. 5
   workup.STIRRINGby stirring at room temperature overnight
6. 6
   workup.ADDITIONTo the reaction mixture was added 0.5 mL of 1 M hydrochloric acid
7. 7
   أخرىthe solvent was evaporated under reduced pressure
8. 8
   أخرىThe obtained residue was purified by preparative HPLC (methanol/0.1% aqueous formic acid solution)

الإجراء التجريبي

To a mixture of 8.2 mg of 7-methyl-4-oxo-1-(tetrahydro-2H-pyran-4-yl)-4,5-dihydro-1H-pyrazolo[4,3-c]quinoline-8-carboxylic acid, 7.7 mg of methyl 3-piperidin-4-yl-benzoate monohydrochloride, 3.4 mg of 1-hydroxybenzotriazole, 7.0 μL of triethylamine, and 1.0 mL of DMF was added 100 mg of PS-Carbodiimide (Biotage), followed by stirring at room temperature overnight. To the reaction mixture were added 75 mg of MP-Carbonate (Biotage), 50 mg of PS-Isocyanate (Biotage), and 0.5 mL of DMF at room temperature, followed by stirring for 2 hours. The reaction mixture was filtered and the filtrate was concentrated under reduced pressure. To the obtained residue were added 0.5 mL of methanol, 0.5 mL of tetrahydrofuran, and 0.5 mL of a 1 M aqueous sodium hydroxide solution, followed by stirring at room temperature overnight. To the reaction mixture was added 0.5 mL of 1 M hydrochloric acid and the solvent was evaporated under reduced pressure. The obtained residue was purified by preparative HPLC (methanol/0.1% aqueous formic acid solution) to obtain 5.8 mg of 3-(1-{[7-methyl-4-oxo-1-(tetrahydro-2H-pyran-4-yl)-4,5-dihydro-1H-pyrazolo[4,3-c]quinolin-8-yl]carbonyl}piperidin-4-yl)benzoic acid.

المصدر