2-Amino-1,3,4-thiadiazole; 1,3,4-Thiadiazol-2-amine; 1,3,4-Thiadiazol-2-ylamine -Drug Synthesis Database

【结构式】

【分子编号】14591

【品名】2-Amino-1,3,4-thiadiazole; 1,3,4-Thiadiazol-2-amine; 1,3,4-Thiadiazol-2-ylamine

【CA登记号】4005-51-0

【分子式】C₂H₃N₃S

【分子量】101.13204

【元素组成】C 23.75% H 2.99% N 41.55% S 31.71%

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)

The synthesis of LY-217896 and its [5-14C]- and uniformly labeled [UL-13C]-isotopomers has been described: The cyclization of thiosemicarbazide (I) with formic acid (II) at 80-90 C gives 2-amino-1,3,4-thiadiazole (III), which is protected with benzyl chloride in refluxing isopropanol to yield 3-benzyl-1,3,4-thiadiazol-2(3H)-imine (IV). The reaction of (IV) with cyanogen bromide by means of NaHCO3 in methanol - water affords N-(3-benzyl-1,3,4-thiadiazol-2(3H)-ylidene)cyanamide (V), which is finally deprotected with AlCl3 in dichloromethane. The [5-14C]-isotopomer is obtained using [14C]-labeled formic acid in the first step of the synthesis, and the [UL-13C]-isotopomer is obtained using [13C]-labeled thiosemicarbazide (I) and [13C]-formic acid. [13C]-Labeled (I) is synthesized by reaction of potassium cyanide-[13C] with sulfur, yielding potassium thiocyanate-[13C], which is reacted with hydrazine to give [13C]-thiosemicarbazide.

参考文献中间体

合成目标

【1】 Wheeler, W.J.; Blanchard, W.B.; The synthesis of 1,3,4-thiadiazol-2-ylcyanamide sodium, a potentially useful anti-influenza agent and its [5-14C] and [UL-13C3] isotopomers. J Label Compd Radiopharm 1992, 31, 7, 495.

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)	12954	1-Hydrazinecarbothioamide; Thiosemicarbazide	79-19-6	CH₅N₃S	详情	详情
(II)	14590	Formic acid	64-18-6	CH₂O₂	详情	详情
(III)	14591	2-Amino-1,3,4-thiadiazole; 1,3,4-Thiadiazol-2-amine; 1,3,4-Thiadiazol-2-ylamine	4005-51-0	C₂H₃N₃S	详情	详情
(IV)	14592	3-benzyl-1,3,4-thiadiazol-2(3H)-imine		C₉H₉N₃S	详情	详情
(V)	14593	N-[3-benzyl-1,3,4-thiadiazol-2(3H)-ylidene]cyanamide		C₁₀H₈N₄S	详情	详情

合成路线2

该中间体在本合成路线中的序号：(XI)

The condensation of (X) with ascomycin (XI) by means of CF3SO3H in N,N-dimethylpivalamide gives the adduct (X), which is finally deprotected with hot aqueous CF3SO3H.

参考文献中间体

合成目标

【1】 Egan, M.A.M.; et al.; Carbon-14 labeling of a potential new immunoregulant agent. J Label Compd Radiopharm 2000, 43, 11, 1095.

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
(X)	22769	[4-(3,5-dimethoxyphenyl)-1-tetrahydro-2-furanyl-1H-imidazol-2-yl]methyl 2,2,2-trichloroethanimidoate		C₁₈H₂₀Cl₃N₃O₄	详情	详情
(XI)	14591	2-Amino-1,3,4-thiadiazole; 1,3,4-Thiadiazol-2-amine; 1,3,4-Thiadiazol-2-ylamine	4005-51-0	C₂H₃N₃S	详情	详情
(XII)	42280	(1R,9S,12S,13R,14S,17R,21S,23S,24R,25S,27R)-12-[(E)-2-((1R,3R,4R)-4-[[4-(3,5-dimethoxyphenyl)-1-tetrahydro-2-furanyl-1H-imidazol-2-yl]methoxy]-3-methoxycyclohexyl)-1-methylethenyl]-17-ethyl-1,14-dihydroxy-23,25-dimethoxy-13,19,21,27-tetramethyl-11,2		C₅₉H₈₇N₃O₁₅	详情	详情

合成路线3

该中间体在本合成路线中的序号：(XI)

Arylation of ascomycin (XI) with the pentavalent bismuthanes (X) under catalysis of cupric acetate produced a mixture of the required indolyl ether (XII) and minor amounts of bis(indolyl) ether (XIII). Finally, after desilylation of (XII) and (XIII) by acid treatment in MeOH, the title monoindolyl ether was isolated by column chromatography.

参考文献中间体

合成目标

【1】 Brands, K.M.J.; et al.; Mild aryl ether formation in the semisynthesis of the novel macrolide immunosuppressant L-732,531. J Org Chem 1998, 63, 19, 6721.
【2】 Sinclair, P.J.; Goulet, M.; Wong, F.; Parsons, W.H.; Goulet, J.; Wyvratt, M.J. (Merck & Co., Inc.); O-Heteroaryl, O-alkylheteroaryl, O-alkenylheteroaryl and O-alkynylheteroaryl macrolides. EP 0532088; JP 1994116274; US 5252732; WO 9305058 .

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
(Xa)	26858	2-[5-(bis(acetoxy)[bis[1-(2-[[tert-butyl(dimethyl)silyl]oxy]ethyl)-1H-indol-5-yl]]-lambda(5)-bismuthanyl)-1H-indol-1-yl]ethyl tert-butyl(dimethyl)silyl ether		C₅₂H₇₈BiN₃O₇Si₃	详情	详情
(Xb)	26859	2-[5-(bis(benzoyloxy)[bis[1-(2-[[tert-butyl(dimethyl)silyl]oxy]ethyl)-1H-indol-5-yl]]-lambda(5)-bismuthanyl)-1H-indol-1-yl]ethyl tert-butyl(dimethyl)silyl ether		C₆₂H₈₂BiN₃O₇Si₃	详情	详情
(XI)	14591	2-Amino-1,3,4-thiadiazole; 1,3,4-Thiadiazol-2-amine; 1,3,4-Thiadiazol-2-ylamine	4005-51-0	C₂H₃N₃S	详情	详情
(XII)	26860	(1R,9S,12S,13R,14S,17R,21S,23S,24R,25S,27R)-12-[(E)-2-((1R,3R,4R)-4-[[1-(2-[[tert-butyl(dimethyl)silyl]oxy]ethyl)-1H-indol-5-yl]oxy]-3-methoxycyclohexyl)-1-methylethenyl]-17-ethyl-1,14-dihydroxy-23,25-dimethoxy-13,19,21,27-tetramethyl-11,28-dioxa-4-azatricyclo[22.3.1.0(4,9)]octacos-18-ene-2,3,10,16-tetrone		C₅₉H₉₂N₂O₁₃Si	详情	详情
(XIII)	26861	(1R,9S,12S,13R,14S,17R,21S,23S,24R,25S,27R)-14-[[1-(2-[[tert-butyl(dimethyl)silyl]oxy]ethyl)-1H-indol-5-yl]oxy]-12-[(E)-2-((1R,3R,4R)-4-[[1-(2-[[tert-butyl(dimethyl)silyl]oxy]ethyl)-1H-indol-5-yl]oxy]-3-methoxycyclohexyl)-1-methylethenyl]-17-ethyl-1-hydroxy-23,25-dimethoxy-13,19,21,27-tetramethyl-11,28-dioxa-4-azatricyclo[22.3.1.0(4,9)]octacos-18-ene-2,3,10,16-tetrone		C₇₅H₁₁₅N₃O₁₄Si₂	详情	详情

Extended Information