PNU-253998

Chemical Name: N-(4-Chlorobenzyl)-1-(4-morpholinyl)-6-(morpholin-4-ylmethyl)-4-oxo-1,4-dihydroquinoline-3-carboxamide
CAS No. 281651-76-1
项目整合开发状态: Preclinical
项目研究机构: Pfizer (Originator)
合成路线:The reductocondensation of 3-bromo-4-fluorobenzaldehyde (I) with morpholine (II) by means of NaBH(OAc)3 in dichloroethane gives 4-(3-bromo-4-fluorobenzyl)morpholine (III),which is condensed with N-methoxy-N-methylacetamide (IV) by means of BuLi in THF to yield 1-[2-fluoro-5-(4-morpholinylmethyl)phenyl]ethanone (V).The reaction of (V) with an excess diethyl carbonate (VI) by means of NaH affords the 3-oxopropanoate derivative (VII),which is treated with triethyl orthoformate (VIII) and Ac2O at 150 C to provide the ethoxymethylene compound (IX).The reaction of (IX) with morpholine-4-amine (X) in ethanol gives the aminomethylene derivative (XI),which is cyclized by means of NaH in hot THF to yield the quinolone-3-carboxylate (XII).Finally,this compound is condensed with 4-chlorobenzylamine (XIII) by heating at 190 C to afford the target quinolone-3-carboxamide.

合成路线:The reductocondensation of 3-bromo-4-fluorobenzaldehyde (I) with morpholine (II) by means of NaBH(OAc)3 in dichloroethane gives 4-(3-bromo-4-fluorobenzyl)morpholine (III),which is condensed with N-methoxy-N-methylacetamide (IV) by means of BuLi in THF to yield 1-[2-fluoro-5-(4-morpholinylmethyl)phenyl]ethanone (V).The reaction of (V) with an excess diethyl carbonate (VI) by means of NaH affords the 3-oxopropanoate derivative (VII),which is treated with triethyl orthoformate (VIII) and Ac2O at 150 C to provide the ethoxymethylene compound (IX).The reaction of (IX) with piperazine-1-amine (X) in ethanol gives the aminomethylene derivative (XI),which is cyclized by means of NaH in hot THF to yield the quinolone-3-carboxylate (XII).Finally,this compound is condensed with 4-chlorobenzylamine (XIII) by heating at 190 C to afford the target quinolone-3-carboxamide.