تفاعل #92758

معادلة التفاعل

8-(cyclohexylmethoxy)-2-methylimidazo[1,2-a]pyridine-3-carboxylic acid

tert-butyl (3R)-3-amino-4-phenylbutanoate

1-hydroxybenzotriazole

diisopropylethylamine

Carbodiimide

triethylammonium

Carbonate

Isocyanate

→

(3R)-3-({[8-(cyclohexylmethoxy)-2-methylimidazo[1,2-a]pyridin-3-yl]carbonyl}amino)-4-phenylbutanoic acid

المردود 61.9%

المذيبات

DMF

ظروف التفاعل

المعالجة

1. 1
   workup.STIRRINGby stirring at room temperature for 2 hours
2. 2
   أخرىThe resin was removed by filtration
3. 3
   تركيزthe filtrate was concentrated under reduced pressure
4. 4
   workup.ADDITIONto the obtained residue were added 100 μl of 1,4-dioxane and 200 μl of a 4 M hydrogen chloride/1,4-dioxane solution
5. 5
   workup.STIRRINGby stirring at room temperature for 20 hours
6. 6
   تركيزThe reaction mixture was concentrated under reduced pressure
7. 7
   أخرىthe obtained residue was purified by preparative HPLC

الإجراء التجريبي

To a mixture of 5.8 mg of 8-(cyclohexylmethoxy)-2-methylimidazo[1,2-a]pyridine-3-carboxylic acid, 7.1 mg of tert-butyl (3R)-3-amino-4-phenylbutanoate, 2.7 mg of 1-hydroxybenzotriazole, 700 μl of DMF, and 19 μl of diisopropylethylamine was added 50 mg of polystyrene N-cyclohexylcarbodiimide-N′-propyloxymethyl (PS-Carbodiimide manufactured by Biotage), followed by stirring at room temperature for 20 hours. To the reaction mixture were added 50 mg of macroporous triethylammonium methylpolystyrene carbonate (MP-Carbonate manufactured by Biotage) and 50 mg of polystyrene methyl isocyanate (PS-Isocyanate manufactured by Biotage), followed by stirring at room temperature for 2 hours. The resin was removed by filtration, the filtrate was concentrated under reduced pressure, and to the obtained residue were added 100 μl of 1,4-dioxane and 200 μl of a 4 M hydrogen chloride/1,4-dioxane solution, followed by stirring at room temperature for 20 hours. The reaction mixture was concentrated under reduced pressure and the obtained residue was purified by preparative HPLC to obtain 5.6 mg of (3R)-3-({[8-(cyclohexylmethoxy)-2-methylimidazo[1,2-a]pyridin-3-yl]carbonyl}amino)-4-phenylbutanoic acid.

المصدر