5-(chloromethyl)-2,4-dihydro-3H-1,2,4-triazol-3-one -Drug Synthesis Database

【结构式】

【分子编号】44196

【品名】5-(chloromethyl)-2,4-dihydro-3H-1,2,4-triazol-3-one

【CA登记号】

【分子式】C₃H₄ClN₃O

【分子量】133.53708

【元素组成】C 26.98% H 3.02% Cl 26.55% N 31.47% O 11.98%

与该中间体有关的原料药合成路线共 3 条

合成路线1 合成路线2 合成路线3

合成路线1

该中间体在本合成路线中的序号：(XXVI)

Synthesis of 250157: Alternatively, the final compound can be obtained by direct condensation of (VI) with chlorotriazolinone (XXVI) in DMF/H2O in the presence of K2CO3 or DIEA. For the obtention of (XXVI), two routes can be followed: 1. Reaction of semicarbazide (XXVII) with orthoester (XXVIII) in MeOH; and 2. Condensation of semicarbazide (XXVII) with benzyloxyacetyl chloride (XXIX) in THF/H2O in the presence of NaOH to provide adduct (XXX), which is then cyclized by means of refluxing NaOH to afford triazolinone (XXXI). Debenzylation of (XXXI) by hydrogenation over Pd/C in MeOH/H2O yields alcohol (XXXII), which is finally treated with thionyl chloride.

参考文献中间体

合成目标

【1】 Castaner, J.; Silvestre, J.S.; Bayes, M.; Sorbera, L.A.; Aprepitant and L-758298. Drugs Fut 2002, 27, 3, 211.
【2】 Cowden, C.J.; et al.; A new synthesis of 1,2,4-triazolin-5-ones: Application to the convergent synthesis of an NK1 antagonist. Tetrahedron Lett 2000, 41, 44, 8661.
【3】 Cowden, C.J. (Merck Sharp & Dohme Ltd.); Process for the preparation of 1,2,4-triazolin-5-one derivs.. WO 0196315 .
【4】 Dolling, U.H.; Wilson, R.D.; Hands, D.; Cottrell, I.F. (Merck Sharp & Dohme Ltd.); Chemical synthesis of morpholine derivs.. WO 9965900 .

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
(VI)	18293	(1R)-1-[3,5-bis(trifluoromethyl)phenyl]ethyl (2R,3S)-3-(4-fluorophenyl)morpholinyl ether; (2R,3S)-2-([(1R)-1-[3,5-bis(trifluoromethyl)phenyl]ethyl]oxy)-3-(4-fluorophenyl)morpholine	171482-05-6	C₂₀H₁₈F₇NO₂	详情	详情
(XXVI)	44196	5-(chloromethyl)-2,4-dihydro-3H-1,2,4-triazol-3-one		C₃H₄ClN₃O	详情	详情
(XXVII)	23944	1-Hydrazinecarboxamide	563-41-7	CH₅N₃O	详情	详情
(XXVIII)	44197	2-chloro-1,1-dimethoxyethyl methyl ether; 2-chloro-1,1,1-trimethoxyethane		C₅H₁₁ClO₃	详情	详情
(XXIX)	10493	2-(Benzyloxy)acetyl chloride; Benzyloxyacetyl chloride	19810-31-2	C₉H₉ClO₂	详情	详情
(XXX)	44193	2-[2-(benzyloxy)acetyl]-1-hydrazinecarboxamide		C₁₀H₁₃N₃O₃	详情	详情
(XXXI)	44194	5-[(benzyloxy)methyl]-2,4-dihydro-3H-1,2,4-triazol-3-one		C₁₀H₁₁N₃O₂	详情	详情
(XXXII)	44195	5-(hydroxymethyl)-2,4-dihydro-3H-1,2,4-triazol-3-one		C₃H₅N₃O₂	详情	详情

合成路线2

该中间体在本合成路线中的序号：(XXVI)

参考文献中间体

合成目标

【1】 Zhao MM, McNamara JM, Ho GJ, et aL 2002. Practical aaymmetric synthesis of aprepitant,apotmt Human NK-1 receptor anUylonist, viaa stereoselective lewis acid-catalyzed trans aoetalization rraction- J Org Chem, 67 (19)t 6743~6747

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
（XLIV)	13188	ethyl 3-chloro-3-oxopropanoate; 2-Ethoxycarbonylacetyl chloride; Ethyl malonyl chloride	36239-09-5	C₅H₇ClO₃	详情	详情
（XLVI）	66104	2-oxo-2-((1-phenylethyl)amino)acetic acid		C₁₀H₁₁NO₃	详情	详情
（XLVII）	11972	(1R)-3-(Methylamino)-1-phenyl-1-propanol; (R)-3-Hydroxy-N-methyl-3-phenyl propylamine	42142-52-9	C₁₀H₁₅NO	详情	详情
（XLVIII）	66105	3-(4-fluorophenyl)-4-((S)-1-phenylethyl)morpholin-2-one hydrochloride		C₁₈H₁₉FClNO₂	详情	详情
（XLIX）	66106	3-(4-fluorophenyl)-4-((R)-1-phenylethyl)morpholin-2-ol		C₁₈H₂₀FNO₂	详情	详情
（L）	66107	(2S)-3-(4-fluorophenyl)-4-((S)-1-phenylethyl)morpholin-2-yl 2,2,2-trichloroacetimidate		C₂₀H₂₀FCl₃N₂O₂	详情	详情
（LI）	66108	(R)-1-(3,5-(trifluoromethyl)phenyl)ethanol		C₁₀H₈F₆O	详情	详情
（LII）	66109	(3R)-2-(1-(3,5-bis(trifluoromethyl)phenyl)ethoxy)-3-(4-fluorophenyl)-4-((R)-1-phenylethyl)morpholine		C₂₈H₂₆F₇NO₂	详情	详情
（XLI）	66101	(2R)-2-(1-(3,5-bis(trifluoromethyl)phenyl)ethoxy)-3-(4-fluorophenyl)morpholine		C₂₀H₁₈F₇NO₂	详情	详情
（LIII）	66110	6-(1-(3,5-bis(trifluoromethyl)phenyl)ethoxy)-5-(4-fluorophenyl)-3,6-dihydro-2H-1,4-oxazine		C₂₀H₁₆F₇NO₂	详情	详情
（LIV）	66111	2-(1-(3,5-bis(trifluoromethyl)phenyl)ethoxy)-3-(4-fluorophenyl)morpholine hydrochloride		C₂₀H₁₉ClF₇NO₂	详情	详情
(X)	18999	4-Fluorophenylacetic acid; 2-(4-Fluorophenyl)acetic acid	405-50-5	C₈H₇FO₂	详情	详情
(XXVI)	44196	5-(chloromethyl)-2,4-dihydro-3H-1,2,4-triazol-3-one		C₃H₄ClN₃O	详情	详情
(XLIII)	66103	1-(4-fluorophenyl)-2,2-dihydroxyethanone		C₈H₇FO₃	详情	详情
(XLV)	10039	(1R)-1-Phenylethylamine; (1R)-1-Phenyl-1-ethanamine.; L-alpha-Phenylethylamine	3886-69-9	C₈H₁₁N	详情	详情

合成路线3

该中间体在本合成路线中的序号：(XXVI)

参考文献中间体

合成目标

【1】 Cowden CJ, Wilson RD, Bishop BC, et a1.2000,Anew synthesis of l.2.4-triuolin-5-onest application to the convergent synthesis of an NKl antagorust.Tetrahedron Lett, 41: 8661~8664

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
(VI)	18293	(1R)-1-[3,5-bis(trifluoromethyl)phenyl]ethyl (2R,3S)-3-(4-fluorophenyl)morpholinyl ether; (2R,3S)-2-([(1R)-1-[3,5-bis(trifluoromethyl)phenyl]ethyl]oxy)-3-(4-fluorophenyl)morpholine	171482-05-6	C₂₀H₁₈F₇NO₂	详情	详情
(XXVI)	44196	5-(chloromethyl)-2,4-dihydro-3H-1,2,4-triazol-3-one		C₃H₄ClN₃O	详情	详情
(XXVIII)	44197	2-chloro-1,1-dimethoxyethyl methyl ether; 2-chloro-1,1,1-trimethoxyethane		C₅H₁₁ClO₃	详情	详情
(XXXIII)	66096	hydrazinecarboxamide hydrochloride		CH₆ClN₃O	详情	详情

Extended Information