DN-1417
Chemical Name: gamma-Butyrolactone-gamma-carbonylhistidylprolinamide citrate; N-[(Tetrahydro-5-oxo-2-furanyl)carbonyl]-L-histidyl-L-prolinamide citrate
CAS No. 63836-94-2 ((S)-isomer)
项目整合开发状态: Phase II
项目研究机构: Takeda (Originator)
合成路线:The reduction of N-benzyloxycarbonylprolinamide (I) with H2 over Pd/c in methanol gives prolinamide (II),which is condensed with N-benzyloxycarbonylhistidyl hydrazide (III) by means of NaNO2 - HCl in ethyl acetate yielding N-benzyloxycarbonylhistidylprolinamide (IV),The hydrolysis of (IV) with HBr in acetic acid affords histidylprolinamide (V),which is finally condensed with gamma-carboxy-gamma-butyrolactone (VI) by means of pentachlorophenol and dicyclohexylcarbodiimide in DMF.Compound (VI) is prepared by reaction of alpha-aminoglutaric acid (VII) with NaNO2 and 2N H2SO4 in water.
合成路线:The condensation of o-chloronitrobenzene (I) with 2-amino-5-methylthiophene-3-carbonitrile (II) by means of lithium hydroxide in DMSO gives 2-(2-nitroanilino)-5-methylthiophene-3-carbonitrile (III).The reductive cyclization of (III) using stannous chloride in aqueous ethanolic hydrochloric acid gives the primary amidine hydrochloride (IV),which is condensed with N-methylpiperazine (V) in a mixture of 4:1 toluene:DMSO.
📌 参考资料/链接：
参考文献标题:Intermediates and process for preparing olanzapine
文献作者:Larsen,S.D.; Stephenson,G.A.; Bunnell,C.A.; Reutzel,S.M.; Nichols,J.R.(Eli Lilly and Company)
参考来源:US 6020487
📄 详细内容
合成路线:The reduction of N-benzyloxycarbonylprolinamide (I) with H2 over Pd/c in methanol gives prolinamide (II),which is condensed with N-benzyloxycarbonylhistidyl hydrazide (III) by means of NaNO2 - HCl in ethyl acetate yielding N-benzyloxycarbonylhistidylprolinamide (IV),The hydrolysis of (IV) with HBr in acetic acid affords histidylprolinamide (V),which is finally condensed with gamma-carboxy-gamma-butyrolactone (VI) by means of pentachlorophenol and dicyclohexylcarbodiimide in DMF.Compound (VI) is prepared by reaction of alpha-aminoglutaric acid (VII) with NaNO2 and 2N H2SO4 in water.
参考文献标题:
文献作者:Fujino,M.; Nishimura,P.; Nagawa,Y.; Fukuda,N.
参考来源:US 4100152
合成路线:The reduction of N-benzyloxycarbonylprolinamide (I) with H2 over Pd/c in methanol gives prolinamide (II),which is condensed with N-benzyloxycarbonylhistidyl hydrazide (III) by means of NaNO2 - HCl in ethyl acetate yielding N-benzyloxycarbonylhistidylprolinamide (IV),The hydrolysis of (IV) with HBr in acetic acid affords histidylprolinamide (V),which is finally condensed with gamma-carboxy-gamma-butyrolactone (VI) by means of pentachlorophenol and dicyclohexylcarbodiimide in DMF.Compound (VI) is prepared by reaction of alpha-aminoglutaric acid (VII) with NaNO2 and 2N H2SO4 in water.
参考文献标题:Synthesis of a series of residue 1-(pyroglutamic acid) analogs of thyrotropin releasing hormone
文献作者:Bauce,L.G.; Goren,H.J.
参考来源:Intl J Pept Protein Res 1979,14(3),216-226