반응 #167001

반응 방정식

DIEA

5-Aza-spiro[2.4]heptane-5,6-dicarboxylic acid 5-tert-butyl ester

HATU

2-Amino-1-(4-bromo-phenyl)-ethanone bis HCl salt

→

6-[2-(4-Bromo-phenyl)-2-oxo-ethylcarbamoyl]-5-aza-spiro[2.4]heptane-5-carboxylic acid tert-butyl ester

수율 67.0%

용매

DMF

ethyl acetate

DMF

반응 조건

후처리

1. 1
   workup.STIRRINGThe reaction was stirred at 0° C. for 40 minutes
2. 2
   세척washed with saturated sodium bicarbonate solution
3. 3
   건조The organic layer was dried (MgSO4)
4. 4
   농축concentrated
5. 5
   기타purified by flash column chromatography (silica gel, 20 to 100% ethyl acetate/hexane)

실험 절차

5-Aza-spiro[2.4]heptane-5,6-dicarboxylic acid 5-tert-butyl ester (350 mg, 1.45 mmol) was mixed with HATU (551 mg, 1.45 mmol) in DMF (5 mL) and the mixture was stirred at room temperature for 30 minutes. 2-Amino-1-(4-bromo-phenyl)-ethanone bis HCl salt (416 mg, 1.45 mmol) in 2 mL DMF was added, followed by DIEA (3.5 eq., 0.88 mL) dropwise at 0° C. The reaction was stirred at 0° C. for 40 minutes. The reaction mixture was diluted in ethyl acetate and washed with saturated sodium bicarbonate solution. The organic layer was dried (MgSO4), concentrated and purified by flash column chromatography (silica gel, 20 to 100% ethyl acetate/hexane) to give 6-[2-(4-Bromo-phenyl)-2-oxo-ethylcarbamoyl]-5-aza-spiro[2.4]heptane-5-carboxylic acid tert-butyl ester (424 mg, 67%). LCMS-ESI−: calc'd for C20H25BrN2O4: 437.33. Found: 460.1 (M+Na+).

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