benzyl (6S)-1-ethyl-4-methyl-1,4-diazepan-6-ylcarbamate -Drug Synthesis Database

【结构式】

【分子编号】53997

【品名】benzyl (6S)-1-ethyl-4-methyl-1,4-diazepan-6-ylcarbamate

【CA登记号】n/a

【分子式】C₁₆H₂₅N₃O₂

【分子量】291.39352

【元素组成】C 65.95% H 8.65% N 14.42% O 10.98%

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)

The protection of the NH2 group of L-serine (I) gives N-(benzyloxycarbonyl)-L-serine (II), which is converted into the N-methylamide (III). The reduction of the amide group of (III) affords the diaminopropanol (IV), which is N-protected to provide the Boc-protected compound (V). The mesylation of the OH group of (V) gives the mesylate (VI), which is treated with ethylamine to yield the triaminopropane (VII). Boc deprotection in (VII) with HCl affords intermediate (VIII), which is submitted to a reductive cyclization with glyoxal and BH3/TEA to provide the perhydro-1,4-diazepine (IX). Cbz deprotection in (IX) by hydrogenation with H2 over Pd/C gives the 1-ethyl-4-methylperhydro-1,4-diazepin-6(R)-amine (X), which is condensed with 5-bromo-2-methoxy-6-(methylamino)pyridine-3-carboxylic acid (XI) by means of ethyl chloroformate and TEA to yield the target amide (XII). Finally, this compound is treated with fumaric acid (XIII) in ethanol to afford the desired fumarate salt.

参考文献中间体

合成目标

【1】 Hirokawa, Y.; et al.; Process development of the synthetic route to (R)-6-amino-1-ethyl-4-methylhexahydro-1,4-diazepine. Org Process Res Dev 2002, 6, 1, 28.

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)	20915	methyl (2S)-2-amino-3-hydroxypropanoate	5680-80-8	C₄H₉NO₃	详情	详情
(II)	51660	methyl (2S)-2-[[(benzyloxy)carbonyl]amino]-3-hydroxypropanoate		C₁₂H₁₅NO₅	详情	详情
(III)	53991	benzyl (1S)-1-(hydroxymethyl)-2-(methylamino)-2-oxoethylcarbamate	n/a	C₁₂H₁₆N₂O₄	详情	详情
(IV)	53992	benzyl (1R)-2-hydroxy-1-[(methylamino)methyl]ethylcarbamate	n/a	C₁₂H₁₈N₂O₃	详情	详情
(V)	53993	benzyl (1R)-2-[(tert-butoxycarbonyl)(methyl)amino]-1-(hydroxymethyl)ethylcarbamate	n/a	C₁₇H₂₆N₂O₅	详情	详情
(VI)	53994	(2R)-2-{[(benzyloxy)carbonyl]amino}-3-[(tert-butoxycarbonyl)(methyl)amino]propyl methanesulfonate	n/a	C₁₈H₂₈N₂O₇S	详情	详情
(VII)	53995	benzyl (1S)-2-[(tert-butoxycarbonyl)(methyl)amino]-1-[(ethylamino)methyl]ethylcarbamate	n/a	C₁₉H₃₁N₃O₄	详情	详情
(VIII)	53996	benzyl (1R)-2-(ethylamino)-1-[(methylamino)methyl]ethylcarbamate	n/a	C₁₄H₂₃N₃O₂	详情	详情
(IX)	53997	benzyl (6S)-1-ethyl-4-methyl-1,4-diazepan-6-ylcarbamate	n/a	C₁₆H₂₅N₃O₂	详情	详情
(X)	17802	(6S)-1-ethyl-4-methyl-1,4-diazepan-6-ylamine; (6S)-1-ethyl-4-methyl-1,4-diazepan-6-amine		C₈H₁₉N₃	详情	详情
(XI)	17801	5-bromo-2-methoxy-6-(methylamino)nicotinic acid		C₈H₉BrN₂O₃	详情	详情
(XII)	53998	5-bromo-N-[(6S)-1-ethyl-4-methyl-1,4-diazepan-6-yl]-2-methoxy-6-(methylamino)nicotinamide	n/a	C₁₆H₂₆BrN₅O₂	详情	详情
(XIII)	23808	Fumaric acid; (E)-2-butenedioic acid	110-17-8	C₄H₄O₄	详情	详情

合成路线2

该中间体在本合成路线中的序号：(XII)

The protection of the NH2 group of L-serine (I) gives N-(benzyloxycarbonyl)-L-serine (II), which is converted into the N-methylamide (III). The reduction of the amide group of (III) affords the diaminopropanol (IV), which is N-protected to provide the Boc-protected compound (V). The mesylation of the OH group of (V) gives the mesylate (VI), which is treated with ethylamine to yield the triaminopropane (VII). The condensation of (VII) with ethyl bromoacetate (VIII) affords the aminoacetate (IX), which is selectively deprotected with HCl to provide the intermediate (X). The cyclization of (X) by means of NaOEt gives the perhydro-1,4-diazepin-2-one (XI), which is reduced with BH3/THF to yield the perhydro-1,4-diazepine (XII). Cbz deprotection in (XII) by hydrogenation with H2 over Pd/C gives the 1-ethyl-4-methylperhydro-1,4-diazepin-6(R)-amine (XIII), which is condensed with 5-bromo-2-methoxy-6-(methylamino)pyridine-3-carboxylic acid (XIV) by means of ethyl chloroformate and TEA to yield the target amide (XV). Finally, this compound is treated with fumaric acid (XVI) in ethanol to afford the desired fumarate salt.

参考文献中间体

合成目标

【1】 Hirokawa, Y.; et al.; Process development of the synthetic route to (R)-6-amino-1-ethyl-4-methylhexahydro-1,4-diazepine. Org Process Res Dev 2002, 6, 1, 28.

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)	20915	methyl (2S)-2-amino-3-hydroxypropanoate	5680-80-8	C₄H₉NO₃	详情	详情
(II)	51660	methyl (2S)-2-[[(benzyloxy)carbonyl]amino]-3-hydroxypropanoate		C₁₂H₁₅NO₅	详情	详情
(III)	53991	benzyl (1S)-1-(hydroxymethyl)-2-(methylamino)-2-oxoethylcarbamate	n/a	C₁₂H₁₆N₂O₄	详情	详情
(IV)	53992	benzyl (1R)-2-hydroxy-1-[(methylamino)methyl]ethylcarbamate	n/a	C₁₂H₁₈N₂O₃	详情	详情
(V)	53993	benzyl (1R)-2-[(tert-butoxycarbonyl)(methyl)amino]-1-(hydroxymethyl)ethylcarbamate	n/a	C₁₇H₂₆N₂O₅	详情	详情
(VI)	53994	(2R)-2-{[(benzyloxy)carbonyl]amino}-3-[(tert-butoxycarbonyl)(methyl)amino]propyl methanesulfonate	n/a	C₁₈H₂₈N₂O₇S	详情	详情
(VII)	53995	benzyl (1S)-2-[(tert-butoxycarbonyl)(methyl)amino]-1-[(ethylamino)methyl]ethylcarbamate	n/a	C₁₉H₃₁N₃O₄	详情	详情
(VIII)	16640	Ethyl 2-bromoacetate; Ethyl bromoacetate	105-36-2	C₄H₇BrO₂	详情	详情
(IX)	53999	ethyl 2-[{(2S)-2-{[(benzyloxy)carbonyl]amino}-3-[(tert-butoxycarbonyl)(methyl)amino]propyl}(ethyl)amino]acetate	n/a	C₂₃H₃₇N₃O₆	详情	详情
(X)	54000	ethyl 2-[[(2R)-2-{[(benzyloxy)carbonyl]amino}-3-(methylamino)propyl](ethyl)amino]acetate	n/a	C₁₈H₂₉N₃O₄	详情	详情
(XI)	54001	benzyl (6S)-4-ethyl-1-methyl-2-oxo-1,4-diazepan-6-ylcarbamate	n/a	C₁₆H₂₃N₃O₃	详情	详情
(XII)	53997	benzyl (6S)-1-ethyl-4-methyl-1,4-diazepan-6-ylcarbamate	n/a	C₁₆H₂₅N₃O₂	详情	详情
(XIII)	17802	(6S)-1-ethyl-4-methyl-1,4-diazepan-6-ylamine; (6S)-1-ethyl-4-methyl-1,4-diazepan-6-amine		C₈H₁₉N₃	详情	详情
(XIV)	17801	5-bromo-2-methoxy-6-(methylamino)nicotinic acid		C₈H₉BrN₂O₃	详情	详情
(XV)	53998	5-bromo-N-[(6S)-1-ethyl-4-methyl-1,4-diazepan-6-yl]-2-methoxy-6-(methylamino)nicotinamide	n/a	C₁₆H₂₆BrN₅O₂	详情	详情
(XVI)	23808	Fumaric acid; (E)-2-butenedioic acid	110-17-8	C₄H₄O₄	详情	详情

Extended Information