LY-377604

6-(4-(2-((((2S)-3-(9H-卡巴唑-4-酰氧基)-2-羟丙基)氨基)-2-甲基丙基苯氧基)吡啶-3-羧酰胺 Chemical Name: 6-[4-[2-[3-(9H-Carbazol-4-yloxy)-2(S)-hydroxypropylamino]-2-methylpropyl]phenoxy]pyridine-3-carboxamide hydrochloride
CAS No. 204592-97-2, 204592-94-9 (free base)
项目整合开发状态: Preclinical
项目研究机构: Lilly (Originator)
合成路线:By condensation of substituted nicotinamide (VI) with the carbazolyoxymethyl-oxirane (XII) in hot methanol/water.The intermediates the nicotinamide (VI) and the oxirane (XII) have been obtained as follows:1.- Nicotinamide (VI): The reaction of 4-hydroxybenzyl alcohol (I) with 2-nitropropane (II) by means of potassium tert-butoxide in hot diglyme gives 4-(2-methyl-2-nitropropyl)phenol (III),which is reduced to the corresponding amino derivative (IV) with H2 over Pd/C in methanol/ethanol/acetic acid.Finally,this compound is condensed with 6-chloronicotinamide (V) by means of K2CO3 in dimethylacetamide/isooctane.2.- Oxirane (XII): The reaction of phenylhydrazine (VII) with cyclohexane-1,3-dione (VIII) by means of NaHCO3 in isopropanol/water gives the monohydrazone (IX),which is cyclized with hotpolyphosphoric acid yielding the 4-hydroxycarbazole (X).Finally,this compound is condensed with the glycidyl 3-nitrophenylsulfonate (XI) by means of K2CO3 in refluxing acetone.