Methyl ethanimidoate; Methyl acetimidate -Drug Synthesis Database

【结构式】

【分子编号】54699

【品名】Methyl ethanimidoate; Methyl acetimidate

【CA登记号】

【分子式】C₃H₇NO

【分子量】73.09472

【元素组成】C 49.3% H 9.65% N 19.16% O 21.89%

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：(V)

The reaction of N6-(benzyloxycarbonyl)-N2--(tert-butoxycarbonyl)-L-lysine (I) with 1H-tetrazol-5-amine (II) by means of BOP and DIEA or NMM in DMF gives the corresponding amide (III), which is hydrogenolyzed with H2 over Pd/C in etyhanol/HOAc to yield N2-(tert-butoxycarbonyl)-N1-(1H-tetrazol-5-yl)-L-lysine (IV). The reaction of (IV) with methyl acetimidate (V) by means of TEA in DMF (or ethyl acetimidate (VI) and NaOH in ethanol) affords the iminomethyl derivative (VII), which is finally deprotected with HCl in dioxane.

参考文献中间体

合成目标

【1】 Hallinan, E.A.; Tsymbalov, S.; Dorn, C.R.; Pitzele, B.S.; Hansen, D.W. Jr.; Synthesis and biological characterization of L-N6-(1-iminoethyl)lysine 5-tetrazole-amide, a prodrug of a selective iNOS inhibitor. J Med Chem 2002, 45, 8, 1686.
【2】 Hallinan, E.A.; Hansen, D.W. Jr.; Tsymbalov, S. (Pharmacia Corp.); Aminotetrazole derivs. useful as nitric oxide synthase inhibitors. EP 0790987; EP 1113011; JP 1998508847; US 5684008; WO 9615120 .

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)	23159	(2S)-6-[[(benzyloxy)carbonyl]amino]-2-[(tert-butoxycarbonyl)amino]hexanoic acid		C₁₉H₂₈N₂O₆	详情	详情
(II)	14092	1H-1,2,3,4-Tetraazol-5-ylamine; 1H-Tetrazol-5-amine; 1H-1,2,3,4-Tetraazol-5-amine; 5-Amino-1H-1,2,3,4-tetrazole	4418-61-5	CH₃N₅	详情	详情
(III)	54697	benzyl (5S)-5-[(tert-butoxycarbonyl)amino]-6-oxo-6-(1H-1,2,3,4-tetraazol-5-ylamino)hexylcarbamate		C₂₀H₂₉N₇O₅	详情	详情
(IV)	54698	tert-butyl (1S)-5-amino-1-[(1H-1,2,3,4-tetraazol-5-ylamino)carbonyl]pentylcarbamate		C₁₂H₂₃N₇O₃	详情	详情
(V)	54699	Methyl ethanimidoate; Methyl acetimidate		C₃H₇NO	详情	详情
(VI)	12831	ethyl ethanimidoate	1000-84-6	C₄H₉NO	详情	详情
(VII)	54700	tert-butyl (1S)-5-(ethanimidoylamino)-1-[(1H-1,2,3,4-tetraazol-5-ylamino)carbonyl]pentylcarbamate		C₁₄H₂₆N₈O₃	详情	详情

合成路线2

该中间体在本合成路线中的序号：(V)

The N-tetrazolyl lysinamide derivative (III) was obtained by acylation of 5-aminotetrazole (II) with Boc-L-lysine(Cbz) (I) using BOP as the coupling reagent. The N-benzyloxycarbonyl protecting group of (III) was then removed by hydrogenation over Pd/C to afford amine (IV), which was subsequently condensed with methyl acetimidate (V) producing amidine (VI). The target compound was finally obtained by N-Boc group cleavage in (VI) under acidic conditions

参考文献中间体

合成目标

【1】 Hallinan, E.A.; Tsymbalov, S.; Dorn, C.R.; Pitzele, B.S.; Hansen, D.W. Jr.; Synthesis and biological characterization of L-N6-(1-iminoethyl)lysine 5-tetrazole-amide, a prodrug of a selective iNOS inhibitor. J Med Chem 2002, 45, 8, 1686.
【2】 Hallinan, E.A.; Hansen, D.W. Jr.; Tsymbalov, S. (Pharmacia Corp.); Aminotetrazole derivs. useful as nitric oxide synthase inhibitors. EP 0790987; EP 1113011; JP 1998508847; US 5684008; WO 9615120 .

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)	23159	(2S)-6-[[(benzyloxy)carbonyl]amino]-2-[(tert-butoxycarbonyl)amino]hexanoic acid		C₁₉H₂₈N₂O₆	详情	详情
(II)	14092	1H-1,2,3,4-Tetraazol-5-ylamine; 1H-Tetrazol-5-amine; 1H-1,2,3,4-Tetraazol-5-amine; 5-Amino-1H-1,2,3,4-tetrazole	4418-61-5	CH₃N₅	详情	详情
(III)	54697	benzyl (5S)-5-[(tert-butoxycarbonyl)amino]-6-oxo-6-(1H-1,2,3,4-tetraazol-5-ylamino)hexylcarbamate		C₂₀H₂₉N₇O₅	详情	详情
(IV)	54698	tert-butyl (1S)-5-amino-1-[(1H-1,2,3,4-tetraazol-5-ylamino)carbonyl]pentylcarbamate		C₁₂H₂₃N₇O₃	详情	详情
(V)	54699	Methyl ethanimidoate; Methyl acetimidate		C₃H₇NO	详情	详情
(VI)	54700	tert-butyl (1S)-5-(ethanimidoylamino)-1-[(1H-1,2,3,4-tetraazol-5-ylamino)carbonyl]pentylcarbamate		C₁₄H₂₆N₈O₃	详情	详情

合成路线3

该中间体在本合成路线中的序号：(V)

Fischer indole cyclization of naltrexone (I) with 4-(cyanomethyl)phenylhydrazine (II) produces the indolomorphinan derivative (III). Subsequent reduction of the cyano group of (III) by catalytic hydrogenation over Raney-nickel produces amine (IV). This is then condensed with methyl acetimidate (V) to furnish the corresponding amidine.

参考文献中间体

合成目标

【1】 Stevens, W.C.; Jones, R.M.; Subramanian, G.; Metzger, T.G.; Ferguson, D.M.; Portoghese, P.S.; Potent and selective indolomorphinan antagonists of the kappa-opioid receptor. J Med Chem 2000, 43, 14, 2759.

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)	25079	(1S,5R,13R,17S)-4-(cyclopropylmethyl)-10,17-dihydroxy-12-oxa-4-azapentacyclo[9.6.1.0(1,13).0(5,17).0(7,18)]octadeca-7(18),8,10-trien-14-one; Naltrexone	16590-41-3	C₂₀H₂₃NO₄	详情	详情
(II)	64330	2-(4-hydrazinophenyl)acetonitrile		C₈H₉N₃	详情	详情
(III)	64331	2-[(1S,2S,13R,21R)-22-(cyclopropylmethyl)-2,16-dihydroxy-14-oxa-11,22-diazaheptacyclo[13.9.1.0~1,13~.0~2,21~.0~4,12~.0~5,10~.0~19,25~]pentacosa-4(12),5,7,9,15(25),16,18-heptaen-7-yl]acetonitrile		C₂₈H₂₇N₃O₃	详情	详情
(IV)	64332	(1S,2S,13R,21R)-7-(2-aminoethyl)-22-(cyclopropylmethyl)-14-oxa-11,22-diazaheptacyclo[13.9.1.0~1,13~.0~2,21~.0~4,12~.0~5,10~.0~19,25~]pentacosa-4(12),5,7,9,15(25),16,18-heptaene-2,16-diol		C₂₈H₃₁N₃O₃	详情	详情
(V)	54699	Methyl ethanimidoate; Methyl acetimidate		C₃H₇NO	详情	详情

Extended Information