methyl 1-hydrazinecarboxylate; methyl carbazate -Drug Synthesis Database

【结构式】

【分子编号】12556

【品名】methyl 1-hydrazinecarboxylate; methyl carbazate

【CA登记号】6294-89-9

【分子式】C₂H₆N₂O₂

【分子量】90.08192

【元素组成】C 26.67% H 6.71% N 31.1% O 35.52%

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：(C)

Reaction of 2-ethyloxazoline (A) with phenol (B) affords the propionamide (I). Treatment of (I) with phosgene yields the imino chloride (II), which is reacted with methylcarbazate to provide the amidrazone (III). Cyclodehydration of (III) gives the triazolone (IV). Alkylation of (IV) with 1-(3-chlorophenyl)-4-(3-chloropropyl) piperazine affords nefazodone, which is isolated as the hydrochloride salt.

参考文献中间体

合成目标

【1】 Fathi, N.H.; et al.; J Heterocycl Chem 1985, 22, 10, 1121.
【2】 Eison, M.S.; Smith, D.W.; Madding, G.D.; Taylor, D.P.; Nefazodone Hydochloride. Drugs Fut 1987, 12, 8, 758.

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
(B)	23540	Phenol	108-95-2	C₆H₆O	详情	详情
(A)	28216	2-ethyl-4,5-dihydro-1,3-oxazole	10431-98-8	C₅H₉NO	详情	详情
(I)	28217	N-(2-phenoxyethyl)propanamide		C₁₁H₁₅NO₂	详情	详情
(II)	28218	N-(2-phenoxyethyl)propanimidoyl chloride		C₁₁H₁₄ClNO	详情	详情
(III)	28219	methyl 2-[(Z)-1-[(2-phenoxyethyl)amino]propylidene]-1-hydrazinecarboxylate		C₁₃H₁₉N₃O₃	详情	详情
(IV)	28220	5-ethyl-4-(2-phenoxyethyl)-2,4-dihydro-3H-1,2,4-triazol-3-one		C₁₂H₁₅N₃O₂	详情	详情
(V)	28221	1-(3-chlorophenyl)-4-(3-chloropropyl)piperazine	39577-43-0	C₁₃H₁₈Cl₂N₂	详情	详情
(C)	12556	methyl 1-hydrazinecarboxylate; methyl carbazate	6294-89-9	C₂H₆N₂O₂	详情	详情

合成路线2

该中间体在本合成路线中的序号：(II)

The cyclization of 1-butyl-6-chloro-5-cyano-3-propyluracil (I) with methoxycarbonylhydrazine (II) in refluxing methanol yields 3-amino-7-butyl-4,6-dioxo-5-propyl-4,5,6,7-tetrahydro-2H-pyrazolo[3,4-d]pyrimidine-2-carboxylic acid ethyl ester (III), which is then methylated with methyl iodide and K2CO3 in DMF.

参考文献中间体

合成目标

【1】 Furukawa, Y.; Maki, Y. (Takeda Chemical Industries, Ltd.); 3-Aminopyrazolo(3,4-d)pyrimidine derivs. and production thereof. EP 0166054 .
【2】 Prous, J.; Castaner, J.; AA-2379. Drugs Fut 1990, 15, 5, 443.

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
(I)	12555	1-Butyl-6-chloro-2,4-dioxo-3-propyl-1,2,3,4-tetrahydro-5-pyrimidinecarbonitrile		C₁₂H₁₆ClN₃O₂	详情	详情
(II)	12556	methyl 1-hydrazinecarboxylate; methyl carbazate	6294-89-9	C₂H₆N₂O₂	详情	详情
(III)	12557	methyl 3-amino-7-butyl-4,6-dioxo-5-propyl-4,5,6,7-tetrahydro-2H-pyrazolo[3,4-d]pyrimidine-2-carboxylate		C₁₄H₂₁N₅O₄	详情	详情

合成路线3

该中间体在本合成路线中的序号：(IV)

The condensation of 1,3-dichloroacetone (I) with ethyl 3-sulfanylpropionate (II) by means of triethylamine in THF gives ethyl 3-(3-chloro-2-oxopropylsulfanyl)propionate (III), which is condensed with ethyl carbazate (IV) by means of Ts-OH in acetonitrile yielding the corresponding hydrazone (V). The cyclization of (V) with SOCl2 in DMF gives the 1,2,3-thiadiazole (VI), which is condensed with 2-aminoethanethiol (A) by means of NaI in dioxane/water afffording the bis thioether (VII). The protection of the amino group of (VII) with Boc2O yields the carbamate (VIII), which is treated with sodium methoxide in methanol to provide sodium thiolate (IX). The condensation of (IX) with the cephem derivative (X) in ethyl acetate/aqueous NaHCO3 gives the expected addition product (XI), which is further condensed with 2-(tert-butoxycarbonylamino)-2-(trityloxyimino)acetic acid (XII) by means of POCl3 in THF yielding the fully protected target compound (XIII). Finally, this compound is deprotected by treatment with TFA and triethylsilane.

参考文献中间体

合成目标

【1】 Hecker, S.J.; Fan, A.T.; Ludwikow, M.; Wang, M.; Cho A.; Glinka, T.W.; New anti-MRSA cephalosporins with a basic aminopyridine at the C-7 position. Bioorg Med Chem Lett 2001, 11, 2, 137.
【2】 Lee, V.J.; Price, M.; Zhang, Z.J.; Fan, A.; Glinka, T.; Chamberland, S.; Cho, A.; Ludwikow, M.; Hecker, S.J.; Liu, N.; Design, synthesis, and SAR of water-soluble dibasic cephalosporins active against resistant Gram-positive bacteria. 39th Intersci Conf Antimicrob Agents Chemother (Sept 26 1999, San Francisco) 1999, Abst F392.

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
(A)	13186	2-Aminoethanethiol; 2-Amino-1-ethanethiol; 2-Aminoethylhydrosulfide; Cysteamine	60-23-1	C₂H₇NS	详情	详情
(I)	63907	1,3-dichloroacetone		C₃H₄Cl₂O	详情	详情
(II)	31837	ethyl 3-sulfanylpropanoate	5466-06-8	C₅H₁₀O₂S	详情	详情
(III)	31838	ethyl 3-[(3-chloro-2-oxopropyl)sulfanyl]propanoate		C₈H₁₃ClO₃S	详情	详情
(IV)	12556	methyl 1-hydrazinecarboxylate; methyl carbazate	6294-89-9	C₂H₆N₂O₂	详情	详情
(V)	31839	methyl 2-((E)-2-chloro-1-[[(3-ethoxy-3-oxopropyl)sulfanyl]methyl]ethylidene)-1-hydrazinecarboxylate		C₁₀H₁₇ClN₂O₄S	详情	详情
(VI)	31840	ethyl 3-[[4-(chloromethyl)-1,2,3-thiadiazol-5-yl]sulfanyl]propanoate		C₈H₁₁ClN₂O₂S₂	详情	详情
(VII)	31841	ethyl 3-[(4-[[(2-aminoethyl)sulfanyl]methyl]-1,2,3-thiadiazol-5-yl)sulfanyl]propanoate		C₁₀H₁₇N₃O₂S₃	详情	详情
(VIII)	31842	ethyl 3-([4-[([2-[(tert-butoxycarbonyl)amino]ethyl]sulfanyl)methyl]-1,2,3-thiadiazol-5-yl]sulfanyl)propanoate		C₁₅H₂₅N₃O₄S₃	详情	详情
(IX)	31843	sodium 4-[([2-[(tert-butoxycarbonyl)amino]ethyl]sulfanyl)methyl]-1,2,3-thiadiazole-5-thiolate		C₁₀H₁₆N₃NaO₂S₃	详情	详情
(X)	15892	benzhydryl (6R,7R)-7-amino-3-[[methyl(dimethylene)-lambda(6)-sulfanyl]oxy]-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylate		C₂₃H₂₄N₂O₄S₂	详情	详情
(XI)	31844	benzhydryl (6R,7R)-7-amino-3-([4-[([2-[(tert-butoxycarbonyl)amino]ethyl]sulfanyl)methyl]-1,2,3-thiadiazol-5-yl]sulfanyl)-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylate		C₃₀H₃₃N₅O₅S₄	详情	详情
(XII)	31845	2-[3-[(tert-butoxycarbonyl)amino]phenyl]-2-[(trityloxy)imino]acetic acid		C₃₂H₃₀N₂O₅	详情	详情
(XIII)	31846	benzhydryl (6R,7R)-3-([4-[([2-[(tert-butoxycarbonyl)amino]ethyl]sulfanyl)methyl]-1,2,3-thiadiazol-5-yl]sulfanyl)-7-([2-[3-[(tert-butoxycarbonyl)amino]phenyl]-2-[(trityloxy)imino]acetyl]amino)-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylate		C₆₂H₆₁N₇O₉S₄	详情	详情

Extended Information