tert-butyl (5S,6S,9S)-6-benzyl-9-(tert-butyl)-5-hydroxy-3-[4-[2-(1-methyl-1-phenylethyl)-2H-1,2,3,4-tetraazol-5-yl]benzyl]-8,11-dioxo-12-oxa-2,3,7,10-tetraazatridecan-1-oate -Drug Synthesis Database

【结构式】

【分子编号】28457

【品名】tert-butyl (5S,6S,9S)-6-benzyl-9-(tert-butyl)-5-hydroxy-3-[4-[2-(1-methyl-1-phenylethyl)-2H-1,2,3,4-tetraazol-5-yl]benzyl]-8,11-dioxo-12-oxa-2,3,7,10-tetraazatridecan-1-oate

【CA登记号】

【分子式】C₄₀H₅₄N₈O₆

【分子量】742.91908

【元素组成】C 64.67% H 7.33% N 15.08% O 12.92%

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：(XI)

Cycloaddition of sodium azide to 4-formylbenzonitrile (I) yielded tetrazole (II), which was protected with 2-phenylpropene (III) in the presence of methanesulfonic acid to give (IV). Subsequent condensation of (IV) with tert-butyl carbazate afforded hydrazone (V), which was further reduced to the benzylhydrazine (VI) employing NaBH3CN and p-toluenesulfonic acid. Opening of the trifluoroacetyl-protected epoxide (VII) with hydrazine (VI) gave hydrazinoalcohol (VIII). After hydrolysis of the trifluoroacetamide group of (VIII) with K2CO3, the resulting amine (IX) was coupled with N-methoxycarbonyl-L-tert-leucine (X) by means of EDC and HOBt to provide amide (XI).

参考文献中间体

合成目标

【1】 Fassler, A.; Bold, G.; Capraro, H.-G.; Lang, M.; Khanna, S.C. (Novartis AG); Antivirally active heterocyclic azahexane derivs.. EP 0900210; JP 1999511177; US 5849911; WO 9740029 .

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)	17552	4-formylbenzonitrile; 4-Cyanobenzaldehyde	105-07-7	C₈H₅NO	详情	详情
(II)	28449	4-(2H-1,2,3,4-tetraazol-5-yl)benzaldehyde	74815-22-8	C₈H₆N₄O	详情	详情
(III)	28450	1-isopropenylbenzene	98-83-9	C₉H₁₀	详情	详情
(IV)	28451	4-[2-(1-methyl-1-phenylethyl)-2H-1,2,3,4-tetraazol-5-yl]benzaldehyde		C₁₇H₁₆N₄O	详情	详情
(V)	28452	tert-butyl 2-((Z)-[4-[2-(1-methyl-1-phenylethyl)-2H-1,2,3,4-tetraazol-5-yl]phenyl]methylidene)-1-hydrazinecarboxylate		C₂₂H₂₆N₆O₂	详情	详情
(VI)	28453	tert-butyl 2-[4-[2-(1-methyl-1-phenylethyl)-2H-1,2,3,4-tetraazol-5-yl]benzyl]-1-hydrazinecarboxylate		C₂₂H₂₈N₆O₂	详情	详情
(VII)	28454	2,2,2-trifluoro-N-[(1S)-1-[(2R)oxiranyl]-2-phenylethyl]acetamide		C₁₂H₁₂F₃NO₂	详情	详情
(VIII)	28455	tert-butyl 2-[(2S,3S)-2-hydroxy-4-phenyl-3-[(2,2,2-trifluoroacetyl)amino]butyl]-2-[4-[2-(1-methyl-1-phenylethyl)-2H-1,2,3,4-tetraazol-5-yl]benzyl]-1-hydrazinecarboxylate		C₃₄H₄₀F₃N₇O₄	详情	详情
(IX)	28456	tert-butyl 2-[(2S,3S)-3-amino-2-hydroxy-4-phenylbutyl]-2-[4-[2-(1-methyl-1-phenylethyl)-2H-1,2,3,4-tetraazol-5-yl]benzyl]-1-hydrazinecarboxylate		C₃₂H₄₁N₇O₃	详情	详情
(X)	23447	(2S)-2-[(methoxycarbonyl)amino]-3,3-dimethylbutyric acid		C₈H₁₅NO₄	详情	详情
(XI)	28457	tert-butyl (5S,6S,9S)-6-benzyl-9-(tert-butyl)-5-hydroxy-3-[4-[2-(1-methyl-1-phenylethyl)-2H-1,2,3,4-tetraazol-5-yl]benzyl]-8,11-dioxo-12-oxa-2,3,7,10-tetraazatridecan-1-oate		C₄₀H₅₄N₈O₆	详情	详情

合成路线2

该中间体在本合成路线中的序号：(XI)

Deprotection of the Boc group of XI) by treatment with HCl furnished hydrazine (XII), which was coupled with N-methoxycarbonyl-L-tert-leucine (X) to afford bisamide (XIII). The alpha,alpha-dimethyl benzyl protecting group of (XIII) was then removed with 80% H2SO4, and the deprotected tetrazole (XIV) was finally alkylated with CH3I to provide the title compound.

参考文献中间体

合成目标

【1】 Fassler, A.; Bold, G.; Capraro, H.-G.; Lang, M.; Khanna, S.C. (Novartis AG); Antivirally active heterocyclic azahexane derivs.. EP 0900210; JP 1999511177; US 5849911; WO 9740029 .

中间体序号	中间体编号	品名	分子式	供应商	用于合成
(X)	23447	(2S)-2-[(methoxycarbonyl)amino]-3,3-dimethylbutyric acid	C₈H₁₅NO₄	详情	详情
(XI)	28457	tert-butyl (5S,6S,9S)-6-benzyl-9-(tert-butyl)-5-hydroxy-3-[4-[2-(1-methyl-1-phenylethyl)-2H-1,2,3,4-tetraazol-5-yl]benzyl]-8,11-dioxo-12-oxa-2,3,7,10-tetraazatridecan-1-oate	C₄₀H₅₄N₈O₆	详情	详情
(XII)	28458	methyl (1S)-1-([[(1S,2S)-1-benzyl-2-hydroxy-3-(1-[4-[2-(1-methyl-1-phenylethyl)-2H-1,2,3,4-tetraazol-5-yl]benzyl]hydrazino)propyl]amino]carbonyl)-2,2-dimethylpropylcarbamate	C₃₅H₄₆N₈O₄	详情	详情
(XIII)	28459	methyl (1S,4S,5S,10S)-4-benzyl-1,10-di(tert-butyl)-5-hydroxy-7-[4-[2-(1-methyl-1-phenylethyl)-2H-1,2,3,4-tetraazol-5-yl]benzyl]-2,9,12-trioxo-13-oxa-3,7,8,11-tetraazatetradec-1-ylcarbamate	C₄₃H₅₉N₉O₇	详情	详情
(XIV)	28460	methyl (1S,4S,5S,10S)-4-benzyl-1,10-di(tert-butyl)-5-hydroxy-2,9,12-trioxo-7-[4-(2H-1,2,3,4-tetraazol-5-yl)benzyl]-13-oxa-3,7,8,11-tetraazatetradec-1-ylcarbamate	C₃₄H₄₉N₉O₇	详情	详情

Extended Information