A-198401

Chemical Name: 11-Amino-3'-N-(cyclopropylmethyl)-3'-N-demethyl-11-deoxy-3-O-deshexopyranosyl-11-[2-(3,4-dichlorophenyl)ethyl]-6-O-methyl-3-O-[4(S)-methyl-2-oxooxazolidin-3-ylcarbonyl]erythromycin A 11-N,12-O-cyclic carbamate
CAS No. 256375-42-5, 361981-34-2 (deleted CAS)
项目整合开发状态: Preclinical
项目研究机构: Abbott (Originator)
合成路线:Protection of 2'-O-acetyl-6-O-methylerythromycin A (I) with chlorotrimethylsilane afforded the 4''-O-trimethylsilyl derivative (II).Subsequent treatment with carbonyldiimidazole and NaH produced the dehydrated imidazolide (III),which was converted to the cyclic carbamate (V) upon reaction with 4-chlorophenethyl amine (IV).Acid hydrolysis of the cladinose moiety gave alcohol (VI),and further condensation with carbonyldiimidazole yielded imidazolide (VII).

合成路线:Coupling of this imidazolide (VII) with the lithium salt of (S)-4-methyloxazolidine-2-one (VIII) at low temperature,followed by acid hydrolysis of the acetate ester furnished carbamate (IX).Mono-N-demethylation of (IX) to give secondary amine (X) was achieved by photochemical reaction with iodine and NaOAc.Finally,reductive alkylation with cyclopropanecarboxaldehyde (XI) in the presence of NaBH3CN produced the title cyclopropylmethylamino derivative.