tert-butyl N-[3-(aminomethyl)benzyl]carbamate; tert-butyl 3-(aminomethyl)benzylcarbamate -Drug Synthesis Database

【结构式】

【分子编号】19169

【品名】tert-butyl N-[3-(aminomethyl)benzyl]carbamate; tert-butyl 3-(aminomethyl)benzylcarbamate

【CA登记号】108467-99-8

【分子式】C₁₃H₂₀N₂O₂

【分子量】236.31408

【元素组成】C 66.07% H 8.53% N 11.85% O 13.54%

与该中间体有关的原料药合成路线共 2 条

合成路线1 合成路线2

合成路线1

该中间体在本合成路线中的序号：(III)

The reaction of m-xylenediamine (I) with triethylamine and di-tert-butyldicarbonate (II) gives the corresponding tert-butyl N-[3-(aminomethyl)benzyl] carbamate hydrochloride (III), which is converted into the tert-butyl N-[3-((acetimidoyl)aminomethyl]benzyl) carbamate hydrochloride (VII) by reaction with S-benzylthioacetimidate hydrochloride (VI). This intermediate (VI) could be obtained by reaction of thioacetamide (IV) with benzyl chloride (V). Finally, compound (VII) is deprotected with HCl to afford the corresponding N-[3-(aminomethyl)benzyl] acetamidine hydrochloride.

参考文献中间体

合成目标

【1】 Itabashi, K.; Takido, T.; An efficient synthesis of unsymmetrical sulfides using liquid-liquid phase transfer catalysis. Synthesis 1987, 817.
【2】 Oplinger, J.A.; Garvey, E.P.; Furfine, E.S.; Shearer, B.G.; Collins, J.L. (Glaxo Wellcome plc); Acetamidine derivs. and their use as inhibitors for the nitric oxide synthase. EP 0799191; JP 1999500711; US 5866612; WO 9619440 .

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)	19167	3-(aminomethyl)benzylamine; [3-(aminomethyl)phenyl]methanamine	1477-55-0	C₈H₁₂N₂	详情	详情
(II)	13214	Di-tert-butyldicarbonate; Dicarbonic acid bis(1,1-dimethylethyl) ester; dicarbonic acid di-tert-butyl ester pyrocarbonic acid di-tert-butyl ester; bis(1,1-dimethylethyl) dicarbonate di-tert-butyl pyrocarbonate	24424-99-5	C₁₀H₁₈O₅	详情	详情
(III)	19169	tert-butyl N-[3-(aminomethyl)benzyl]carbamate; tert-butyl 3-(aminomethyl)benzylcarbamate	108467-99-8	C₁₃H₂₀N₂O₂	详情	详情
(IV)	19170	ethanethioamide	62-55-5	C₂H₅NS	详情	详情
(V)	19171	1-(Chloromethyl)benzene; Benzyl chloride	100-44-7	C₇H₇Cl	详情	详情
(VI)	19172	benzyl ethanimidothioate		C₉H₁₁NS	详情	详情
(VII)	19173	tert-butyl 3-[(ethanimidoylamino)methyl]benzylcarbamate		C₁₅H₂₃N₃O₂	详情	详情

合成路线2

该中间体在本合成路线中的序号：(IX)

Protection of the C-7 hydroxyl group of 14-b-hydroxy-10-deacetyl baccatin III (VIII) with triethylsilyl chloride and imidazole yielded silyl ether (IX). Then, the 1,14-diol of (IX) was converted to cyclic carbonate (X) by treatment with diphosgene in the presence of pyridine. Subsequent selective acetylation of (X) at C-10 hydroxyl group with acetyl chloride in the presence of LiN(SiMe3)2 afforded ester (XI). The title taxoid was then obtained by further coupling of (XI) with b-lactam (VII) using LiN(SiMe3)2 in THF at low temperature, followed by desilylation with HF in pyridine.

参考文献中间体

合成目标

【1】 Toyoshi, T.; Nomura, T.; Ogawa, A.; et al.; A four-week intravenous toxicity study of flecainide acetate in rats with a two-week recovery phase. Clin Rep 1994, 28, 6, 13.

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
(VII)	21743	tert-butyl (2S,3R)-2-[(1S)-2,2-dimethylcyclopropyl]-4-oxo-3-[(triisopropylsilyl)oxy]-1-azetidinecarboxylate		C₂₂H₄₁NO₄Si	详情	详情
(VIII)	21744	(1R,2S,3R,4S,7R,9S,10S,12R,15R,16S)-4-(acetoxy)-1,9,12,15,16-pentahydroxy-10,14,17,17-tetramethyl-11-oxo-6-oxatetracyclo[11.3.1.0(3,10).0(4,7)]heptadec-13-en-2-yl benzoate		C₂₉H₃₆O₁₁	详情	详情
(IX)	19169	tert-butyl N-[3-(aminomethyl)benzyl]carbamate; tert-butyl 3-(aminomethyl)benzylcarbamate	108467-99-8	C₁₃H₂₀N₂O₂	详情	详情
(X)	19160	(1S,2S,3R,4S,7R,9S,10S,12R,15R,16S)-4-(acetoxy)-12,15-dihydroxy-10,14,20,20-tetramethyl-11,18-dioxo-9-[(triethylsilyl)oxy]-6,17,19-trioxapentacyclo[11.6.1.0(1,16).0(3,10).0(4,7)]icos-13-en-2-yl benzoate		C₃₆H₄₈O₁₂Si	详情	详情
(XI)	19161	(1S,2S,3R,4S,7R,9S,10S,12R,15R,16S)-4,12-bis(acetoxy)-15-hydroxy-10,14,20,20-tetramethyl-11,18-dioxo-9-[(triethylsilyl)oxy]-6,17,19-trioxapentacyclo[11.6.1.0(1,16).0(3,10).0(4,7)]icos-13-en-2-yl benzoate		C₃₈H₅₀O₁₃Si	详情	详情

Extended Information