Реакция #87199

Уравнение реакции

DIEA

(S)-2-amino-3-(benzyloxy)-N-((S)-3-(4-methoxyphenyl)-1-(((S)-1-((R)-2-methyloxiran-2-yl)-1-oxo-3-phenylpropan-2-yl)amino)-1-oxopropan-2-yl)propanamide TFA salt

2-morpholinoacetic acid

HATU

→

(S)-3-(benzyloxy)-N-((S)-3-(4-methoxyphenyl)-1-(((S)-1-((R)-2-methyloxiran-2-yl)-1-oxo-3-phenylpropan-2-yl)amino)-1-oxopropan-2-yl)-2-(2-morpholinoacetamido)propanamide

Выход 32.7%

Растворители

DMF

Условия реакции

Обработка

1. 1
   Другоеthen quenched with sodium bicarbonate (sat.)
2. 2
   Экстракцияextracted with ethyl acetate (2×)
3. 3
   Сушкаdried with sodium sulfate
4. 4
   Фильтрацияfiltered
5. 5
   Концентрированиеconcentrated
6. 6
   ДругоеPurification by column chromatography (3:1 DCM/ethyl acetate+0-10% methanol)

Методика

To (S)-2-amino-3-(benzyloxy)-N-((S)-3-(4-methoxyphenyl)-1-(((S)-1-((R)-2-methyloxiran-2-yl)-1-oxo-3-phenylpropan-2-yl)amino)-1-oxopropan-2-yl)propanamide TFA salt (2.94 mmol assumed) was added 2-morpholinoacetic acid (647 mg, 4.46 mmol), HATU (1.86 g, 4.91 mmol), and DMF (5 mL). The mixture was cooled to 0° C. and DIEA (3.10 mL, 17.8 mmol) was added. The reaction mixture was stirred at ambient temperature for 30 min then quenched with sodium bicarbonate (sat.), extracted with ethyl acetate (2×), dried with sodium sulfate, filtered, and concentrated. Purification by column chromatography (3:1 DCM/ethyl acetate+0-10% methanol) provided (S)-3-(benzyloxy)-N-((S)-3-(4-methoxyphenyl)-1-(((S)-1-((R)-2-methyloxiran-2-yl)-1-oxo-3-phenylpropan-2-yl)amino)-1-oxopropan-2-yl)-2-(2-morpholinoacetamido)propanamide (660 mg, 28% over 5 steps) as an amorphous colorless solid. MS (EI) for C38H46N4O8, found 687.4 (MH+).

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