N-(2-aminoethyl)-N-methylamine -Drug Synthesis Database

【结构式】

【分子编号】27777

【品名】N-(2-aminoethyl)-N-methylamine

【CA登记号】109-81-9

【分子式】C₃H₁₀N₂

【分子量】74.12588

【元素组成】C 48.61% H 13.6% N 37.79%

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：(B)

Treatment of 1,4-dichloro-5,8-dihydroxy-9,10-anthracenedione (I) with K2CO3 and benzyl bromide gives the benzyl ether (II) in refluxing acetone, which, followed by treatment with 2-[(2-hydrazinoethyl)amino]ethanol in anhydrous Me2SO, gives product (III). Treatment of product (III) with excess [(2-aminoethyl)amino]methane in refluxing pyridine gives the «two armed» compound, which, followed by treatment with Pearlman's catalyst in glacial AcOH, gives the target compound CI-937.

参考文献中间体

合成目标

【1】 Proc Amer Assoc Cancer Res 1984, 25, 1, 352.
【2】 Hoshi, A.; CI-937 and CI-942. Drugs Fut 1986, 11, 3, 179.
【3】 Showalter, H.D.H.; Johnson, J.L.; Werbel, L.M.; Leopold, W.R.; Jackson, R.C.; Elslager, E.F.; 5-[(Aminoalkyl)amino]-substituted anthra[1, 9-cd]pyrazol-6(2H)-ones as novel anticancer agents. Synthesis and biological evaluation. J Med Chem 1984, 27, 3, 253-5.

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
(A)	27775	2-[(2-hydrazinoethyl)amino]-1-ethanol		C₄H₁₃N₃O	详情	详情
(B)	27777	N-(2-aminoethyl)-N-methylamine	109-81-9	C₃H₁₀N₂	详情	详情
(I)	27773	1,4-dichloro-5,8-dihydroxyanthra-9,10-quinone		C₁₄H₆Cl₂O₄	详情	详情
(II)	27774	1,4-bis(benzyloxy)-5,8-dichloroanthra-9,10-quinone		C₂₈H₁₈Cl₂O₄	详情	详情
(III)	27776	7,10-bis(benzyloxy)-5-chloro-2-[2-[(2-hydroxyethyl)amino]ethyl]dibenzo[cd,g]indazol-6(2H)-one		C₃₂H₂₈ClN₃O₄	详情	详情

合成路线2

该中间体在本合成路线中的序号：(X)

ZK-807834 is obtained by condensation of the diaryl ether (I) with the phenol (II) by means of K2CO3 to afford the bisaryl ether (III). Reaction of the cyano group of (III), first with HCl in ethanol and then with ammonia, yields the corresponding amidino compound (IV), which is finally demethylated with HBr.

参考文献中间体

合成目标

【2】 Discovery of N-[2-[5-[amino(imino)methyl]-2-hydroxyphenoxy]-3,5-difluoro-6-[3-(4,5-dihydro-1-methyl-1H-imidazol-2-yl)phenoxy]pyridin-4-yl]-N-methylglycine (ZK-807834): A potent, selective, and orally active inhibitor of the blood coagulation enzyme factor. J Med Chem 1998, 41, 19, 3557.
【1】 Ricart-Diaz, M.; Castaner, J.; ZK-807834. Drugs Fut 2002, 27, 8, 748.
【3】 Buckman, B.O.; Davey, D.D.; Guilford, W.J.; Morrissey, M.M.; Ng, H.P.; Phillips, G.B.; Wu, S.C.; Xu, W. (Berlex Laboratories, Inc.); Benzamidine derivs. their preparation and their use as anti-coagulants. EP 0813525; US 5691364; WO 9628427 .

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)	54575	2-[[2-(5-cyano-2-methoxyphenoxy)-3,5,6-trifluoro-4-pyridinyl](methyl)amino]acetamide		C₁₆H₁₃F₃N₄O₃	详情	详情
(II)	54576	2-(3-methoxyphenyl)-1-methyl-4,5-dihydro-1H-imidazole; methyl 3-(1-methyl-4,5-dihydro-1H-imidazol-2-yl)phenyl ether		C₁₁H₁₄N₂O	详情	详情
(III)	54578	2-[{2-(5-cyano-2-methoxyphenoxy)-3,5-difluoro-6-[3-(1-methyl-4,5-dihydro-1H-imidazol-2-yl)phenoxy]-4-pyridinyl}(methyl)amino]acetamide		C₂₆H₂₄F₂N₆O₄	详情	详情
(IV)	54579	2-[{2-{5-[amino(imino)methyl]-2-methoxyphenoxy}-3,5-difluoro-6-[3-(1-methyl-4,5-dihydro-1H-imidazol-2-yl)phenoxy]-4-pyridinyl}(methyl)amino]acetamide		C₂₆H₂₇F₂N₇O₄	详情	详情
(V)	54571	Pentafluoropyridine; Perfluoropyridine	700-16-3	C₅F₅N	详情	详情
(VI)	54572	2-(methylamino)acetamide		C₃H₈N₂O	详情	详情
(VII)	54573	2-[methyl(2,3,5,6-tetrafluoro-4-pyridinyl)amino]acetamide		C₈H₇F₄N₃O	详情	详情
(VIII)	54574	3-hydroxy-4-methoxybenzonitrile	52805-46-6	C₈H₇NO₂	详情	详情
(IX)	36250	3-methoxybenzonitrile	1527-89-5	C₈H₇NO	详情	详情
(X)	27777	N-(2-aminoethyl)-N-methylamine	109-81-9	C₃H₁₀N₂	详情	详情
(XI)	54575	2-[[2-(5-cyano-2-methoxyphenoxy)-3,5,6-trifluoro-4-pyridinyl](methyl)amino]acetamide		C₁₆H₁₃F₃N₄O₃	详情	详情

合成路线3

该中间体在本合成路线中的序号：(II)

The reaction of N-(tert-butoxycarbonyl)-L-phenylalanine-N-carboxyanhydride (I) with N-methylethylenediamine (II) gives the phenyalaninamide (III), which is condensed with the N-protected chiral azetidinone (IV) by means of Cs2CO3 to yield the diaminopropionic acid derivative (V). The condensation of (V) with glycine tert-butyl ester (VI) by means of BOP and DIEA affords the peptide (VII), which, after deprotection with H2 over Pd/C, is condensed with 4-O-benzyl-L-tyrosine (VIII) by means of BOP and DIEA giving the acyclic precursor (IX). The deprotection of (IX) with TFA, followed by cyclization by means of EDC, HOAt, DIEA and DCM in DMF provides the protected cyclic precursor (X), which is finally deprotected by hydrogenation with H2 over Pd black in ethanol.

参考文献中间体

合成目标

【1】 DeHaven, R.; Dang, T.; Daubert, J.; Yaksh, T.L.; Zhang, L.; Goodman, M.; Shreder, K.; Umeno, H.; Synthesis and biological activity of a novel methylamine-bridged enkephalin analogue (MABE): A new route to cyclic peptides and peptidomimetics. J Med Chem 1998, 41, 14, 2631.

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)	27837	tert-butyl (4S)-4-benzyl-2,5-dioxo-1,3-oxazolidine-3-carboxylate	142955-51-9	C₁₅H₁₇NO₅	详情	详情
(II)	27777	N-(2-aminoethyl)-N-methylamine	109-81-9	C₃H₁₀N₂	详情	详情
(III)	27838	tert-butyl (1S)-1-benzyl-2-[[2-(methylamino)ethyl]amino]-2-oxoethylcarbamate		C₁₇H₂₇N₃O₃	详情	详情
(IV)	27845	benzyl (3R)-2-oxooxetanylcarbamate		C₁₁H₁₁NO₄	详情	详情
(V)	27839	(6S,13R)-6-benzyl-13-[[(benzyloxy)carbonyl]amino]-2,2,11-trimethyl-4,7-dioxo-3-oxa-5,8,11-triazatetradecan-14-oic acid		C₂₈H₃₈N₄O₇	详情	详情
(VI)	27841	tert-butyl 2-aminoacetate;tert-butyl glycinate;Glycine tert-butyl ester	6456-74-2	C₆H₁₃NO₂	详情	详情
(VII)	27840	tert-butyl (6S,13R)-6-benzyl-13-[[(benzyloxy)carbonyl]amino]-2,2,11-trimethyl-4,7,14-trioxo-3-oxa-5,8,11,15-tetraazaheptadecan-17-oate		C₃₄H₄₉N₅O₈	详情	详情
(VIII)	27842	(2S)-2-[[(benzyloxy)carbonyl]amino]-3-[4-(benzyloxy)phenyl]propionic acid		C₂₄H₂₃NO₅	详情	详情
(IX)	27843	tert-butyl (6S,13R)-6-benzyl-13-([(2S)-2-[[(benzyloxy)carbonyl]amino]-3-[4-(benzyloxy)phenyl]propanoyl]amino)-2,2,11-trimethyl-4,7,14-trioxo-3-oxa-5,8,11,15-tetraazaheptadecan-17-oate		C₅₀H₆₄N₆O₁₀	详情	详情
(X)	27844	benzyl (1S)-2-[[(6S,12R)-6-benzyl-1-methyl-5,8,11-trioxo-1,4,7,10-tetraazacyclotridecan-12-yl]amino]-1-[4-(benzyloxy)benzyl]-2-oxoethylcarbamate		C₄₁H₄₆N₆O₇	详情	详情

Extended Information