　 -Drug Synthesis Database

【结构式】

【分子编号】41054

【品名】　

【CA登记号】

【分子式】C₆₉H₁₂₅N₁₁O₁₅

【分子量】1348.81664

【元素组成】C 61.44% H 9.34% N 11.42% O 17.79%

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：(IX)

Reaction of the labeled chiral bromoacetylbornanesultam (I) with benzophenone imine (II) and DIEA in hot acetonitrile gives the imine (III), which is enantioselectively alkylated with isopropyl iodide and n-BuLi yielding the L-valine derivative (IV). Treatment of (IV) with HCl in THF in order to eliminate the diphenylmethylene group affords compound (V) with a free amino group that by protection with Boc2O in THF provides the L-valine derivative (VI). The hydrolysis of (VI) with LiOH in THF/water affords labeled N-(tert-butoxycarbonyl)-L-valine (VII), which is condensed with the decapeptide (VIII) by means of BOP and NMM in dichloromethane providing the linear undecapeptide (IX).

参考文献中间体

合成目标

【1】 Metz, Y.; Kohler, B.; Burtscher, P.; Voges, R.; Wenger, R.; Synthesis of [S-[1-C-14]Val(7)]VALSPODAR application of (+)/(-)-[C-13,14(N)]BABS and (+)/(-)-[C-13,14(N)]DPMGBS, part 4. J Label Compd Radiopharm 2000, 43, 3, 205.

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
	19369	2-iodopropane	75-30-9	C₃H₇I	详情	详情
(I)	41048	(1R)-4-(2-bromoacetyl)-10,10-dimethyl-3lambda(6)-thiatricyclo[5.2.1.0(1,5)]decane-3,3-dione		C₁₃H₁₉BrO₃S	详情	详情
(I)	45254	(1R)-4-(2-bromoacetyl)-10,10-dimethyl-3lambda(6)-thiatricyclo[5.2.1.0(1,5)]decane-3,3-dione		C₁₃H₁₉BrO₃S	详情	详情
(II)	32024	diphenylmethanimine	1013-88-3	C₁₃H₁₁N	详情	详情
(III)	41049	(1R)-4-[2-[(dibenzylene)amino]acetyl]-10,10-dimethyl-3lambda(6)-thiatricyclo[5.2.1.0(1,5)]decane-3,3-dione		C₂₆H₂₉NO₃S	详情	详情
(III)	45255	(1R)-4-[2-[(dibenzylene)amino]acetyl]-10,10-dimethyl-3lambda(6)-thiatricyclo[5.2.1.0(1,5)]decane-3,3-dione		C₂₆H₂₉NO₃S	详情	详情
(IV)	41050	(1R)-4-[(2S)-2-[(dibenzylene)amino]-3-methylbutanoyl]-10,10-dimethyl-3lambda(6)-thiatricyclo[5.2.1.0(1,5)]decane-3,3-dione		C₂₉H₃₅NO₃S	详情	详情
(IV)	45256	(1R)-4-[(2S)-2-[(dibenzylene)amino]-3-methylbutanoyl]-10,10-dimethyl-3lambda(6)-thiatricyclo[5.2.1.0(1,5)]decane-3,3-dione		C₂₉H₃₅NO₃S	详情	详情
(V)	41051	(1R)-4-[(2S)-2-amino-3-methylbutanoyl]-10,10-dimethyl-3lambda(6)-thiatricyclo[5.2.1.0(1,5)]decane-3,3-dione		C₁₆H₂₇NO₃S	详情	详情
(V)	45257	(1R)-4-[(2S)-2-amino-3-methylbutanoyl]-10,10-dimethyl-3lambda(6)-thiatricyclo[5.2.1.0(1,5)]decane-3,3-dione		C₁₆H₂₇NO₃S	详情	详情
(VI)	41052	tert-butyl (1S)-1-[[(1R)-10,10-dimethyl-3,3-dioxo-3lambda(6)-thiatricyclo[5.2.1.0(1,5)]dec-4-yl]carbonyl]-2-methylpropylcarbamate		C₂₁H₃₅NO₅S	详情	详情
(VI)	45258	tert-butyl (1S)-1-[[(1R)-10,10-dimethyl-3,3-dioxo-3lambda(6)-thiatricyclo[5.2.1.0(1,5)]dec-4-yl]carbonyl]-2-methylpropylcarbamate		C₂₁H₃₅NO₅S	详情	详情
(VII)	19733	(2S)-2-[(tert-butoxycarbonyl)amino]-3-methylbutyric acid		C₁₀H₁₉NO₄	详情	详情
(VII)	45259	(2S)-2-[(tert-butoxycarbonyl)amino]-3-methylbutyric acid		C₁₀H₁₉NO₄	详情	详情
(VIII)	41053			C₅₉H₁₀₈N₁₀O₁₂	详情	详情
(IX)	41054			C₆₉H₁₂₅N₁₁O₁₅	详情	详情
(IX)	45260	methyl (6S,12S,15S,18S,21S,24R,27S,30S,33S,36S)-36-[(1R,2R,4E)-1-hydroxy-2-methyl-4-hexenyl]-12,18,27,30-tetraisobutyl-6,15,33-triisopropyl-2,2,8,11,17,21,24,26,29,32,35-undecamethyl-4,7,10,13,16,19,22,25,28,31,34-undecaoxo-3-oxa-5,8,11,14,17,20,23,		C₆₉H₁₂₅N₁₁O₁₅	详情	详情

合成路线2

该中间体在本合成路线中的序号：(IX)

The reaction of (IX) first with NaOH in ethanol to hydrolyze the terminal ester group, and then with TFA to eliminate the terminal tert-butoxycarbonyl group gives the fully deprotected peptide (X), which is cyclized by means of BOP and NMM in dichloromethane yielding the cyclic peptide (XI). Finally, this compound is oxidized by the modified Pfitzer-Moffat method with DMSO and DCC in tert-butyl methyl ether.

参考文献中间体

合成目标

【1】 Metz, Y.; Kohler, B.; Burtscher, P.; Voges, R.; Wenger, R.; Synthesis of [S-[1-C-14]Val(7)]VALSPODAR application of (+)/(-)-[C-13,14(N)]BABS and (+)/(-)-[C-13,14(N)]DPMGBS, part 4. J Label Compd Radiopharm 2000, 43, 3, 205.

中间体序号	中间体编号	品名	分子式	供应商	用于合成
(IX)	41054		C₆₉H₁₂₅N₁₁O₁₅	详情	详情
(X)	41055		C₆₃H₁₁₅N₁₁O₁₃	详情	详情
(XI)	15475	(3S,6S,9S,12R,15S,18S,21S,24S,30S,33S)-33-[(1R,2R,4E)-1-hydroxy-2-methyl-4-hexenyl]-6,9,18,24-tetraisobutyl-3,21,30-triisopropyl-1,4,7,10,12,15,19,25,28-nonamethyl-1,4,7,10,13,16,19,22,25,28,31-undecaazacyclotritriacontane-2,5,8,11,14,17,20,23,26,29,32-undecone	C₆₃H₁₁₃N₁₁O₁₂	详情	详情

Extended Information