tert-butyl (1S,2S)-1-formyl-2-methylbutylcarbamate -Drug Synthesis Database

【结构式】

【分子编号】34733

【品名】tert-butyl (1S,2S)-1-formyl-2-methylbutylcarbamate

【CA登记号】

【分子式】C₁₁H₂₁NO₃

【分子量】215.29268

【元素组成】C 61.37% H 9.83% N 6.51% O 22.29%

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：(I)

The reductive condensation of N-Boc-L-isoleucinal (I) with glycine methyl ester (II) using sodium triacetoxyborohydride afforded secondary amine (III), which was further reductively condensed with 1-naphthaldehyde (IV), yielding tertiary amine (V). After basic hydrolysis of the methyl ester group of (V), the resulting carboxylic acid (VI) was coupled with L-methionine methyl ester (VII) by means of EDC and HOBt to give peptide (VIII). Subsequent deprotection of the Boc group of (VII) with HCl in cold EtOAc furnished the required intermediate (IX).

参考文献中间体

合成目标

【1】 Anthony, N.J.; Desolms, S.J.; Gomez, R.P.; Graham, S.L.; Hutchinson, J.H.; Stokker, G.E. (Merck & Co., Inc.); Thio-free inhibitors of farnesyl-protein transferase. JP 1998508005; US 5652257; WO 9610034 .

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)	34733	tert-butyl (1S,2S)-1-formyl-2-methylbutylcarbamate		C₁₁H₂₁NO₃	详情	详情
(II)	17568	methyl 2-aminoacetate		C₃H₇NO₂	详情	详情
(III)	34734	methyl 2-([(2S,3S)-2-[(tert-butoxycarbonyl)amino]-3-methylpentyl]amino)acetate		C₁₄H₂₈N₂O₄	详情	详情
(IV)	12314	1-Naphthaldehyde	66-77-3	C₁₁H₈O	详情	详情
(V)	34735	methyl 2-[[(2S,3S)-2-[(tert-butoxycarbonyl)amino]-3-methylpentyl](1-naphthylmethyl)amino]acetate		C₂₅H₃₆N₂O₄	详情	详情
(VI)	34736	2-[[(2S,3S)-2-[(tert-butoxycarbonyl)amino]-3-methylpentyl](1-naphthylmethyl)amino]acetic acid		C₂₄H₃₄N₂O₄	详情	详情
(VII)	17950	D-Methionine methyl ester; methyl (2S)-2-amino-4-(methylsulfanyl)butanoate hydrochloride	21691-49-6	C₆H₁₃NO₂S	详情	详情
(VIII)	34737	methyl (6S,12S)-2,2-dimethyl-6-[(1S)-1-methylpropyl]-12-[2-(methylsulfanyl)ethyl]-8-(1-naphthylmethyl)-4,10-dioxo-3-oxa-5,8,11-triazatridecan-13-oate		C₃₀H₄₅N₃O₅S	详情	详情
(IX)	34738	methyl (2S)-2-([2-[[(2S,3S)-2-amino-3-methylpentyl](1-naphthylmethyl)amino]acetyl]amino)-4-(methylsulfanyl)butanoate		C₂₅H₃₇N₃O₃S	详情	详情

合成路线2

该中间体在本合成路线中的序号：(I)

The reductive condensation of N-Boc-L-isoleucinal (I) with glycine methyl ester (II) using sodium triacetoxyborohydride afforded secondary amine (III), which was further reductively condensed with 1-naphthaldehyde (IV), yielding tertiary amine (V). After basic hydrolysis of the methyl ester group of (V), the resulting carboxylic acid (VI) was coupled with L-methionine methyl ester (VII) by means of EDC and HOBt to give peptide (VIII). Subsequent deprotection of the Boc group of (VIII) with HCl in cold EtOAc furnished the required intermediate (IX).

参考文献中间体

合成目标

【1】 Anthony, N.J.; Desolms, S.J.; Gomez, R.P.; Graham, S.L.; Hutchinson, J.H.; Stokker, G.E. (Merck & Co., Inc.); Thio-free inhibitors of farnesyl-protein transferase. JP 1998508005; US 5652257; WO 9610034 .

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)	34733	tert-butyl (1S,2S)-1-formyl-2-methylbutylcarbamate		C₁₁H₂₁NO₃	详情	详情
(II)	17568	methyl 2-aminoacetate		C₃H₇NO₂	详情	详情
(III)	34734	methyl 2-([(2S,3S)-2-[(tert-butoxycarbonyl)amino]-3-methylpentyl]amino)acetate		C₁₄H₂₈N₂O₄	详情	详情
(IV)	12314	1-Naphthaldehyde	66-77-3	C₁₁H₈O	详情	详情
(V)	34735	methyl 2-[[(2S,3S)-2-[(tert-butoxycarbonyl)amino]-3-methylpentyl](1-naphthylmethyl)amino]acetate		C₂₅H₃₆N₂O₄	详情	详情
(VI)	34736	2-[[(2S,3S)-2-[(tert-butoxycarbonyl)amino]-3-methylpentyl](1-naphthylmethyl)amino]acetic acid		C₂₄H₃₄N₂O₄	详情	详情
(VII)	17950	D-Methionine methyl ester; methyl (2S)-2-amino-4-(methylsulfanyl)butanoate hydrochloride	21691-49-6	C₆H₁₃NO₂S	详情	详情
(VIII)	34737	methyl (6S,12S)-2,2-dimethyl-6-[(1S)-1-methylpropyl]-12-[2-(methylsulfanyl)ethyl]-8-(1-naphthylmethyl)-4,10-dioxo-3-oxa-5,8,11-triazatridecan-13-oate		C₃₀H₄₅N₃O₅S	详情	详情
(IX)	34738	methyl (2S)-2-([2-[[(2S,3S)-2-amino-3-methylpentyl](1-naphthylmethyl)amino]acetyl]amino)-4-(methylsulfanyl)butanoate		C₂₅H₃₇N₃O₃S	详情	详情

合成路线3

该中间体在本合成路线中的序号：(VIII)

L-5,5-Dimethylthiazolidine-4-carboxylic acid (I) was protected as the N-Boc derivative (II) by treatment with Boc2O and subsequently coupled with L-methionine methyl ester (III) employing EDC and HOBt. The resulting Boc-dipeptide (IV) was then deprotected with trifluoroacetic acid to give (V). On the other hand, Boc-isoleucine (VI) was converted to the N-methoxy amide (VII) by condensation with N,O-dimethylhydroxylamine in the presence of O-benzotriazolyl tetramethyluronium hexafluorophosphate. Reduction of (VII) with LiAlH4 in cold Et2O produced the corresponding aldehyde (VIII). Reductive condensation of thiazolidine (V) with aldehyde (VIII) yielded adduct (IX). The Boc group of (IX) was then deprotected with trifluoroacetic acid to give (X).

参考文献中间体

合成目标

【1】 Dong, Z.X.; Kim, S.H. (Biomeasure Inc.); Inhibitors of prenyl transferases. WO 9800409 .

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)	34776	(4R)-5,5-dimethyl-1,3-thiazolidine-4-carboxylic acid	72778-00-8	C₆H₁₁NO₂S	详情	详情
(II)	34777	(4R)-3-(tert-butoxycarbonyl)-5,5-dimethyl-1,3-thiazolidine-4-carboxylic acid		C₁₁H₁₉NO₄S	详情	详情
(III)	17950	D-Methionine methyl ester; methyl (2S)-2-amino-4-(methylsulfanyl)butanoate hydrochloride	21691-49-6	C₆H₁₃NO₂S	详情	详情
(IV)	38786	tert-butyl (4R)-4-([[(1S)-1-(methoxycarbonyl)-3-(methylsulfanyl)propyl]amino]carbonyl)-5,5-dimethyl-1,3-thiazolidine-3-carboxylate		C₁₇H₃₀N₂O₅S₂	详情	详情
(V)	38787	methyl (2S)-2-([[(4R)-5,5-dimethyl-1,3-thiazolidin-4-yl]carbonyl]amino)-4-(methylsulfanyl)butanoate		C₁₂H₂₂N₂O₃S₂	详情	详情
(VI)	30009	(2S,3S)-2-[(tert-butoxycarbonyl)amino]-3-methylpentanoic acid	13139-16-7	C₁₁H₂₁NO₄	详情	详情
(VII)	38788	tert-butyl (1S,2S)-1-[[methoxy(methyl)amino]carbonyl]-2-methylbutylcarbamate	3350-19-4	C₁₃H₂₆N₂O₄	详情	详情
(VIII)	34733	tert-butyl (1S,2S)-1-formyl-2-methylbutylcarbamate		C₁₁H₂₁NO₃	详情	详情
(IX)	38789	methyl (2S)-2-[[((4R)-3-[(2S,3S)-2-[(tert-butoxycarbonyl)amino]-3-methylpentyl]-5,5-dimethyl-1,3-thiazolidin-4-yl)carbonyl]amino]-4-(methylsulfanyl)butanoate		C₂₃H₄₃N₃O₅S₂	详情	详情
(X)	38790	methyl (2S)-2-[([(4R)-3-[(2S,3S)-2-amino-3-methylpentyl]-5,5-dimethyl-1,3-thiazolidin-4-yl]carbonyl)amino]-4-(methylsulfanyl)butanoate		C₁₈H₃₅N₃O₃S₂	详情	详情

Extended Information