ICI-200880

4-N-(4-氯苯基)磺酰基-1-N-[(2S)-3-甲基-1-氧代-1-[[(2S)-1-(1,1,1-三氟-4-甲基-2-氧代戊烷-3-基)吡咯烷-2-羰基]氨基]丁烷-2-基]苯-1,4-二甲酰胺Chemical Name: 1(RS)-N-[4-[N-(4-Chlorophenylsulfonyl)carbamoyl]benzoyl]-L-valyl-N-[2-methyl-1-(trifluoroacetyl)propyl]-L-prolinamide
CAS No. 105080-50-0, 105120-02-3 ((R)-isomer), 105120-70-5 ((S)-isomer)
项目整合开发状态: Phase II
项目研究机构: AstraZeneca (Originator)
合成路线:The synthetic sequence used for the manufacture of ICI 200,880 is as follows:Carbodiimide-mediated coupling of acid (I) with amine (II) followed by ester hydrolysis with HCl affords acid (III).The other key intermediate,amino alcohol (VI),is prepared via alkylation of nitro-alkane (IV) with trifluoroacetaldehyde followed by reduction of the resulting nitro alcohol (V).Coupling of acid (III) with amino alcohol (VI) followed by oxidation with KMnO4 affords ICI 200,880.Since ICI 200,880 is an amorphous solid,it cannot be purified by crystallization.However,when acid (III) is purified by crystallization as its calcium salt and amino alcohol (VI) is purified by flash distillation,then the final coupling and oxidation proceed to yield ICI 200,880 of excellent purity.