L-372662
Chemical Name: 1-[1-[2-Methoxy-4-[1-(2-methyl-1-oxidopyridin-3-ylmethyl)piperidin-4-yloxy]benzoyl]piperidin-4-yl]-2,4-dihydro-1H-3,1-benzoxazin-2-one
CAS No. 162045-26-3
项目整合开发状态: Preclinical
项目研究机构: Merck & Co. (Originator)
合成路线:1) 2-Aminobenzyl alcohol (I) was condensed with N-tert-butoxycarbonyl-4-piperidone (II) in toluene with azeotropical removal of water,and the resulting imine (III) was reduced with sodium cyanoborohydride to yield the secondary amine (IV).Further treatment of (IV) with triphosgene in the presence of N,N-diisopropyl ethylamine (DIEA) produced the benzoxazinone (V),which was then deprotected with HCl in EtOAc to give piperidine (VI).
合成路线:2) Acidic removal of the tert-butyl carbamate from (XII) gave piperidine (XIII).3) Ethyl 2-methyl nicotinate (XIV) was reduced with diisobutylaluminum hydride (DIBAL-H) to the alcohol (XV).Treatment of (XV) with SOCl2 in CH2Cl2 gave chloride (XVI),which was isolated as the stable HCl salt.Liberation of the base,followed by reaction with 3-chloroperbenzoic acid in CHCl3,provided the N-oxide (XVII).4) Finally,piperidine (XIII) was alkylated with chloride (XVII) in the presence of DIEA in DMF at 50 C to yield the target compound.
📌 参考资料/链接：
参考文献标题:Benzoxazinone and benzopyrimidinone piperidinyl tocolytic oxytocin receptor antagonists
文献作者:Bock,M.G.; Evans,B.E.; Hobbs,D.W.; Williams,P.D.; Anderson,P.S.; Freidinger,R.M.; Pettibone,D.J.(Merck & Co.,Inc.)
参考来源:EP 0714299; JP 1997500134; US 5665719; WO 9502405
📄 详细内容
合成路线:1) 2-Aminobenzyl alcohol (I) was condensed with N-tert-butoxycarbonyl-4-piperidone (II) in toluene with azeotropical removal of water,and the resulting imine (III) was reduced with sodium cyanoborohydride to yield the secondary amine (IV).Further treatment of (IV) with triphosgene in the presence of N,N-diisopropyl ethylamine (DIEA) produced the benzoxazinone (V),which was then deprotected with HCl in EtOAc to give piperidine (VI).
合成路线:2) Acidic removal of the tert-butyl carbamate from (XII) gave piperidine (XIII).3) Ethyl 2-methyl nicotinate (XIV) was reduced with diisobutylaluminum hydride (DIBAL-H) to the alcohol (XV).Treatment of (XV) with SOCl2 in CH2Cl2 gave chloride (XVI),which was isolated as the stable HCl salt.Liberation of the base,followed by reaction with 3-chloroperbenzoic acid in CHCl3,provided the N-oxide (XVII).4) Finally,piperidine (XIII) was alkylated with chloride (XVII) in the presence of DIEA in DMF at 50 C to yield the target compound.
参考文献标题:Development of orally active oxytocin antagonists: Studies on 1-(1-[4-[1-(2-methyl-1-oxidopyridin-3-ylmethyl)piperidin-4-yloxy]-2-methoxybenzoyl]piperidin-4-yl)-1,4-dihydrobenz[d][1,3]oxazin-2-one (L-372,662) and related pyridines
文献作者:Bell,I.M.; Erb,J.M.; Freidinger,R.M.; Gallicchio,S.N.; Guare,J.P.; Guidotti,M.T.; Halpin,R.A.; Hobbs,D.W.; Homnick,C.F.; Kuo,M.S.; Lis,E.V.; Mathre,D.J.; Michelsomn,S.R.; Pawluczyk,J.M.; Pettibone,D.J.; Reiss,D.R.; Vickers,S.; et al.
参考来源:J Med Chem 1998,41(12),2146
产品链接: CAS No. 162045-26-3››