Piclamilast, RPR-73401, RP-73401

合成路线:The alkylation of isovanillin (I) with cyclopentyl bromide (II) by means of K2CO3 in refluxing ethanol (or hot DMF) gives the 4-cyclopentyloxy-3-methoxybenzaldehyde (III),which is oxidized with H2O2 and NaOH (or NaClO2 in AcOH/water) yielding the carboxylic acid (IV).The reaction of (IV) with SOCl2 and DMF in refluxing toluene affords the acyl chloride (V),which is finally condensed with 3,5-dichloropyridine-4-amine (VI) by means of potassium tert-butoxide in toluene or NaH in THF or by heating at the melting point.The intermediate 3,5-dichloropyridine-4-amine (VI) is obtained by chlorination of pyridine-4-amine (VII) with HCl and H2O2 at 70 C.

参考文献标题:Selective type IV phosphodiesterase inhibitors as antiasthmatic agents.The syntheses and biological activities of 3-(cyclopentyloxy)-4-methoxybenzamides and analogues
文献作者:Ashton,M.J.; Cook,D.C.; Fenton,G.; Karlsson,J.A.; Palfreyman,M.N.; Raeburn,D.; Ratcliffe,A.J.; Souness,J.E.; Thurairatnam,S.; Vicker,N.
参考来源:J Med Chem 1994,37(11),1696


合成路线:The alkylation of isovanillin (I) with cyclopentyl bromide (II) by means of K2CO3 in refluxing ethanol (or hot DMF) gives the 4-cyclopentyloxy-3-methoxybenzaldehyde (III),which is oxidized with H2O2 and NaOH (or NaClO2 in AcOH/water) yielding the carboxylic acid (IV).The reaction of (IV) with SOCl2 and DMF in refluxing toluene affords the acyl chloride (V),which is finally condensed with 3,5-dichloropyridine-4-amine (VI) by means of potassium tert-butoxide in toluene or NaH in THF or by heating at the melting point.The intermediate 3,5-dichloropyridine-4-amine (VI) is obtained by chlorination of pyridine-4-amine (VII) with HCl and H2O2 at 70 C.
参考文献标题:Process development of the PDE IV inhibitor 3-(cyclopentyloxy)-N-(3,5-dichloropyrid-4-yl)-4-methoxybenzamide
文献作者:Cook,D.C.; Walton,J.B.; Pemberton,C.; Jones,R.H.; McFarlane,I.M.; Thompson,D.M.; Thatcher,A.A.; Kabir,H.; Lythgoe,D.J.
参考来源:Org Process Res Dev 1998,2(3),157


产品链接: CAS No. 144035-83-6››