methyl (Z)-[(methoxycarbonyl)amino](methylsulfanyl)methylidenecarbamate -Drug Synthesis Database

【结构式】

【分子编号】28696

【品名】methyl (Z)-[(methoxycarbonyl)amino](methylsulfanyl)methylidenecarbamate

【CA登记号】

【分子式】C₆H₁₀N₂O₄S

【分子量】206.22248

【元素组成】C 34.95% H 4.89% N 13.58% O 31.03% S 15.55%

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：(III)

An improved synthesis of [14C]-peldesine has been reported: The reaction of S-methyl-[14C]-isothiourea (I) with methyl chloroformate (II) by means of tetrabutylammonium bromide in dichloromethane gives N,N'-bis(methoxycarbonyl)-S-methyl-[14C]-isothiourea (III). This compound is condensed with 3-amino-4-(3-pyridylmethyl)-1H-pyrrole-2-carboxylic acid methyl ester (IV) by means of acetic acid in methanol yielding the labeled guanidine (V). The cyclization of (V) by means of sodium methoxide in methanol affords the carbamate precursor (VI), which is finally deprotected with NaOH in hot water.

参考文献中间体

合成目标

【1】 Elliott, A.J.; Kwong, C.D.; Montgomery, J.A.; An improved synthesis of 9-(3-pyridylmethyl)-[2-14C]-9-deazaguanine. J Label Compd Radiopharm 1998, 41, 10, 879.

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)	10272	[[Amino(imino)methyl]sulfanyl]methane	2986-19-8	C₂H₆N₂S	详情	详情
(I)	44636	[[amino(imino)methyl]sulfanyl]methane		C₂H₆N₂S	详情	详情
(II)	16993	methyl chlorocarbonate;Carbonochloridic acid methyl ester；[(chlorocarbonyl)oxy]methane；methyl chloroformate	79-22-1	C₂H₃ClO₂	详情	详情
(III)	28696	methyl (Z)-[(methoxycarbonyl)amino](methylsulfanyl)methylidenecarbamate		C₆H₁₀N₂O₄S	详情	详情
(III)	45292	methyl (Z)-[(methoxycarbonyl)amino](methylsulfanyl)methylidenecarbamate		C₆H₁₀N₂O₄S	详情	详情
(IV)	16030	methyl 3-amino-4-(3-pyridinylmethyl)-1H-pyrrole-2-carboxylate		C₁₂H₁₃N₃O₂	详情	详情
(V)	28697	methyl 3-([bis[(methoxycarbonyl)amino]methylene]amino)-4-(3-pyridinylmethyl)-1H-pyrrole-2-carboxylate		C₁₇H₁₉N₅O₆	详情	详情
(V)	45293	methyl 3-([bis[(methoxycarbonyl)amino]methylene]amino)-4-(3-pyridinylmethyl)-1H-pyrrole-2-carboxylate		C₁₇H₁₉N₅O₆	详情	详情
(VI)	28698	methyl 4-oxo-7-(3-pyridinylmethyl)-4,5-dihydro-3H-pyrrolo[3,2-d]pyrimidin-2-ylcarbamate		C₁₄H₁₃N₅O₃	详情	详情
(VI)	45294	methyl 4-oxo-7-(3-pyridinylmethyl)-4,5-dihydro-3H-pyrrolo[3,2-d]pyrimidin-2-ylcarbamate		C₁₄H₁₃N₅O₃	详情	详情

合成路线2

该中间体在本合成路线中的序号：(V)

The condensation between 4-(acetylamino)thiophenol (I) and 5-chloro-2-nitroaniline (II) produced the diaryl sulfide (III). Nitro group reduction in (III) employing SnCl2 gave the phenylenediamine (IV), which was cyclized to the benzimidazole (VI) upon treatment with N,N'-bis(methoxycarbonyl)-S-methylisothiourea (V). Hydrolysis of the acetamido group of (VI) with HCl in MeOH afforded aniline (VII). This was acylated with N-Boc-alanine (VIII) in the presence of EDC to yield amide (IX). The N-Boc protecting group of (IX) was finally removed by treatment with trifluoroacetic acid.

参考文献中间体

合成目标

【1】 Lewis, G.S.; Nolan, J.; Davis, P.D.; Naylor, M.A.; Thomson, P.; Hill, S.A.; Benzimidazole carbamates: A new structural class of vascular targeting agents. Proc Amer Assoc Cancer Res 2001, 42, Abst 2000.
【2】 Davis, P.D. (Angiogene Pharmaceuticals Ltd.); Benzimidazole vascular damaging agents. EP 1140078; WO 0041669 .

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)	34329	N-(4-sulfanylphenyl)acetamide	1126-81-4	C₈H₉NOS	详情	详情
(II)	15709	5-chloro-2-nitrophenylamine; 5-chloro-2-nitroaniline	1635-61-6	C₆H₅ClN₂O₂	详情	详情
(III)	51869	N-[4-[(3-amino-4-nitrophenyl)sulfanyl]phenyl]acetamide		C₁₄H₁₃N₃O₃S	详情	详情
(IV)	51870	N-[4-[(3,4-diaminophenyl)sulfanyl]phenyl]acetamide		C₁₄H₁₅N₃OS	详情	详情
(V)	28696	methyl (Z)-[(methoxycarbonyl)amino](methylsulfanyl)methylidenecarbamate		C₆H₁₀N₂O₄S	详情	详情
(VI)	51871	methyl 5-[[4-(acetamido)phenyl]sulfanyl]-1H-benzimidazol-2-ylcarbamate		C₁₇H₁₆N₄O₃S	详情	详情
(VII)	51872	methyl 5-[(4-aminophenyl)sulfanyl]-1H-benzimidazol-2-ylcarbamate		C₁₅H₁₄N₄O₂S	详情	详情
(VIII)	26450	Boc-L-Alanine;(S)-2-((tert-butoxycarbonyl)amino)propanoic acid;N-Boc-L-alanine; (2S)-2-[(tert-butoxycarbonyl)amino]propionic acid	15761-38-3	C₈H₁₅NO₄	详情	详情
(IX)	51873	methyl 5-[[4-([(2S)-2-[(tert-butoxycarbonyl)amino]propanoyl]amino)phenyl]sulfanyl]-1H-benzimidazol-2-ylcarbamate		C₂₃H₂₇N₅O₅S	详情	详情

合成路线3

该中间体在本合成路线中的序号：(VII)

The reaction of 4-chloro-2-amino-1-nitrobenzene (I) with sodium phenylmercaptide (A) in DMF gives 2-amino-4-phenylthio-1-nitrobenzene (II), which is treated with acetic anhydride to yield 2-acetamido-4-phenylthio-1-nitrobenzene (III). This product is oxidized with peracetic acid in methanol giving 2-amino-4-phenylsulfinyl-1-nitrobenzene (V). Then the nitro group is reduced with H2 over Pd/C in methanol yielding 1,2-diamino-4-phenylsulfinylbenzene (VI). This product is finally condensed with N,N'-bis(methoxycarbonyl)-S-methylisothiourea (VII) in ethanol - water - acetic acid. The isothiourea (VII) is obtained by reaction of S-methylisothiouronium sulfate (VIII) with methyl chloroformate (B) by means of KOH in water

参考文献中间体

合成目标

【1】 Beard, C.C.; et al. (Syntex, Inc.); DE 2363351 .
【2】 Castaner, J.; Bogan, J.A.; Oxfendazole. Drugs Fut 1976, 1, 9, 438.

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)	16993	methyl chlorocarbonate;Carbonochloridic acid methyl ester；[(chlorocarbonyl)oxy]methane；methyl chloroformate	79-22-1	C₂H₃ClO₂	详情	详情
(A)	60753	sodium benzenethiolate		C₆H₅NaS	详情	详情
(I)	15709	5-chloro-2-nitrophenylamine; 5-chloro-2-nitroaniline	1635-61-6	C₆H₅ClN₂O₂	详情	详情
(II)	60754	2-nitro-5-(phenylsulfanyl)aniline; 2-nitro-5-(phenylsulfanyl)phenylamine		C₁₂H₁₀N₂O₂S	详情	详情
(III)	60755	N-[2-nitro-5-(phenylsulfanyl)phenyl]acetamide		C₁₄H₁₂N₂O₃S	详情	详情
(IV)	60756	N-[2-nitro-5-(phenylsulfinyl)phenyl]acetamide		C₁₄H₁₂N₂O₄S	详情	详情
(V)	60757	2-nitro-5-(phenylsulfinyl)aniline; 2-nitro-5-(phenylsulfinyl)phenylamine		C₁₂H₁₀N₂O₃S	详情	详情
(VI)	60758	4-(phenylsulfinyl)-1,2-benzenediamine; 2-amino-4-(phenylsulfinyl)phenylamine		C₁₂H₁₂N₂OS	详情	详情
(VII)	28696	methyl (Z)-[(methoxycarbonyl)amino](methylsulfanyl)methylidenecarbamate		C₆H₁₀N₂O₄S	详情	详情
(VIII)	10272	[[Amino(imino)methyl]sulfanyl]methane	2986-19-8	C₂H₆N₂S	详情	详情

Extended Information