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【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

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.

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

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.

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