Реакция #92757

Уравнение реакции

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

(S)-(+)-2-phenylglycine methyl ester hydrochloride

1-hydroxybenzotriazole

diisopropylethylamine

Carbodiimide

triethylammonium

Carbonate

Isocyanate

→

(2S)-({[8-(cyclohexylmethoxy)-2-methylimidazo[1,2-a]pyridin-3-yl]carbonyl}amino)(phenyl)acetic acid

Выход 79.0%

Растворители

DMF

Условия реакции

Обработка

1. 1
   workup.STIRRINGby stirring at room temperature for 2 hours
2. 2
   ДругоеThe resin was removed by filtration
3. 3
   Концентрированиеthe filtrate was concentrated under reduced pressure
4. 4
   workup.ADDITIONto the obtained residue were added 100 μl of THF, 200 μl of methanol, and 50 μl of a 1 M aqueous sodium hydroxide solution
5. 5
   workup.STIRRINGby stirring at 50° C. for 20 hours
6. 6
   workup.WAITTo the reaction mixture that had been left
7. 7
   Температураto be cooled to room temperature
8. 8
   workup.ADDITIONwere added 0.5 ml of water and 50 μl of 1 M hydrochloric acid
9. 9
   Концентрированиеfollowed by concentration under reduced pressure
10. 10
    ДругоеThe obtained residue was purified by preparative HPLC

Методика

To a mixture of 5.8 mg of 8-(cyclohexylmethoxy)-2-methylimidazo[1,2-a]pyridine-3-carboxylic acid, 6.1 mg of (S)-(+)-2-phenylglycine methyl ester hydrochloride, 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. Subsequently, 50 mg of macroporous triethylammonium methylpolystyrene carbonate (MP-Carbonate manufactured by Biotage) and 50 mg of polystyrene methyl isocyanate (PS-Isocyanate manufactured by Biotage) were added thereto, 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 THF, 200 μl of methanol, and 50 μl of a 1 M aqueous sodium hydroxide solution, followed by stirring at 50° C. for 20 hours. To the reaction mixture that had been left to be cooled to room temperature were added 0.5 ml of water and 50 μl of 1 M hydrochloric acid, followed by concentration under reduced pressure. The obtained residue was purified by preparative HPLC to obtain 6.7 mg of (2S)-({[8-(cyclohexylmethoxy)-2-methylimidazo[1,2-a]pyridin-3-yl]carbonyl}amino)(phenyl)acetic acid.

Источник