1-Ethyl-3-(3'-dimethylaminopropyl)carbodiimide → Ethyl 3-[5-(5-{3-cyano-4-[(1-methylethyl)oxy]phenyl}-1,2,4-oxadiazol-3-yl)-1H-indol-2-yl]propanoate

EDCI (187 mg) and HOBT (149 mg) were added to a solution of 3-cyano-4-[(1-methylethyl)oxy]benzoic acid (100 mg) in THF (5 mL). The mixture was stirred at room temperature for 1 hour followed by addition of ethyl 3-{5-[(Z)-(hydroxyamino)(imino)methyl]-1H-indol-2-yl}propanoate (D31) (201 mg). The resulting mixture was stirred at room temperature for 2 hrs followed by addition of TBAF (510 mg). The reaction vessel was sealed and heated in Biotage Initiator to 120° C. for 2 hrs. After cooling the reaction, THF was removed. The residue was dissolved in EtOAc. The organic solution was washed with saturated aqueous sodium bicarbonate solution. The organic solution was dried over anhydrous sodium sulfate. The dried solution was concentrated. The residue was purified by column chromatography to afford ethyl 3-[5-(5-{3-cyano-4-[(1-methylethyl)oxy]phenyl}-1,2,4-oxadiazol-3-yl)-1H-indol-2-yl]propanoate (D114) (68 mg). The product was directly used in the next step without identification.

1. stirringThe resulting mixture was stirred at room temperature for 2 hrs
2. customThe reaction vessel was sealed
3. temperatureheated in Biotage Initiator to 120° C. for 2 hrs
4. temperatureAfter cooling
5. customwas removed
6. dissolutionThe residue was dissolved in EtOAc
7. washThe organic solution was washed with saturated aqueous sodium bicarbonate solution
8. dry with materialThe organic solution was dried over anhydrous sodium sulfate
9. concentrationThe dried solution was concentrated
10. customThe residue was purified by column chromatography

ORDレコード

ord-49a78cead4d74485a14630ef1fcf0008

出典データセット

uspto-grants-2012_07

DOI

10.6084/m9.figshare.5104873.v1

特許番号

US08217028B2