L-372662-药物合成数据库

【药物名称】L-372662

化学结构式(Chemical Structure):

参考文献No.	25988
标题:	Benzoxazinone and benzopyrimidinone piperidinyl tocolytic oxytocin receptor antagonists
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.)
来源:	EP 0714299; JP 1997500134; US 5665719; WO 9502405

合成路线图解说明: 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).

合成路线图解说明: 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No.	467359
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
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.
来源:	J Med Chem 1998,41(12),2146

合成路线图解说明: 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).

合成路线图解说明: 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.