2-(methylamino)acetamide -Drug Synthesis Database

【结构式】

【分子编号】54572

【品名】2-(methylamino)acetamide

【CA登记号】

【分子式】C₃H₈N₂O

【分子量】88.1094

【元素组成】C 40.9% H 9.15% N 31.79% O 18.16%

与该中间体有关的原料药合成路线共 4 条

合成路线1 合成路线2 合成路线3 合成路线4

合成路线1

该中间体在本合成路线中的序号：(III)

The 2-(hydroxymethyl)penem (I) is transformed into the corresponding mesylate (II), which is then condensed with sarcosinamide (III), to afford adduct (IV). The O-silyl group of (IV) is removed by treatment with tetrabutylammonium fluoride, yielding alcohol (V). Finally, the allyl ester group of (V) is cleaved in the presence of palladium and triphenylphosphine to furnish the target carboxylic acid.

参考文献中间体

合成目标

【3】 Altamura, M.; Arcamone, F.M.; Perrotta, E.; Pestellini, V.; Sbraci, P.; Cascio, G. (Lusofarmaco; Menarini Industrie Farma Riunite Srl); Penem derivs., their preparation and pharmaceutical compsns. containing them. EP 0660837; JP 1996501543; WO 9406803 .
【1】 Pestellini, V.; Perrotta, E.; Arcamone, F.; Sbraci, P.; Altamura, M.; 2-Substituted penems with amino acid-related side chains: Synthesis and antibacterial activity of a new series of beta-lactam antibiotics. J Med Chem 1995, 38, 21, 4244.
【2】 Altamura, M.; et al.; Synthesis and antibacterial activity of MEN 10700, a new penem antibiotic. Bioorg Med Chem Lett 1995, 5, 6, 555.

中间体序号	中间体编号	品名	分子式	供应商	用于合成
(I)	58252	allyl (5R,6S)-6-((1R)-1-{[tert-butyl(dimethyl)silyl]oxy}ethyl)-3-(hydroxymethyl)-7-oxo-4-thia-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylate	C₁₈H₂₉NO₅SSi	详情	详情
(II)	58253	allyl (5R,6S)-6-((1R)-1-{[tert-butyl(dimethyl)silyl]oxy}ethyl)-3-{[(methylsulfonyl)oxy]methyl}-7-oxo-4-thia-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylate	C₁₉H₃₁NO₇S₂Si	详情	详情
(III)	54572	2-(methylamino)acetamide	C₃H₈N₂O	详情	详情
(IV)	58254	allyl (5R,6S)-3-{[(2-amino-2-oxoethyl)(methyl)amino]methyl}-6-((1R)-1-{[tert-butyl(dimethyl)silyl]oxy}ethyl)-7-oxo-4-thia-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylate	C₂₁H₃₅N₃O₅SSi	详情	详情
(V)	58255	allyl (5R,6S)-3-{[(2-amino-2-oxoethyl)(methyl)amino]methyl}-6-[(1R)-1-hydroxyethyl]-7-oxo-4-thia-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylate	C₁₅H₂₁N₃O₅S	详情	详情

合成路线2

该中间体在本合成路线中的序号：(VI)

In a related method, the 4-acetoxy-azetidinone (I) is reacted with 2-chlorothioacetic acid (II) in the presence of ZnI2 to give the (chloroacetylthio)azetidinone (III). Nitrogen acylation in (III) by means of allyl oxalyl chloride produces (IV), which undergoes ring closure to the penem (V) in the presence of triethyl phosphite in boiling toluene. Displacement of chloride (V) with sarcosinamide (VI) yields adduct (VII). After desilylation of (VII) to (VIII) by means of tetrabutylammonium fluoride, palladium-catalyzed allyl ester cleavage leads to the title compound.

参考文献中间体

合成目标

【1】 Arcamone, F.M.; et al.; Synthesis and biological activity of the penem antibiotic MEN 10700 and its orally absorbed ester MEN 11505. J Antibiot 2000, 53, 10, 1086.

中间体序号	中间体编号	品名	分子式	供应商	用于合成
(I)	11687	(2R,3R)-3-((1R)-1-[[tert-butyl(dimethyl)silyl]oxy]ethyl)-4-oxoazetanyl acetate	C₁₃H₂₅NO₄Si	详情	详情
(II)	58256	2-chloroethanethioic S-acid	C₂H₃ClOS	详情	详情
(III)	58257	S-[(2R,3S)-3-((1R)-1-{[tert-butyl(dimethyl)silyl]oxy}ethyl)-4-oxoazetidinyl] 2-chloroethanethioate	C₁₃H₂₄ClNO₃SSi	详情	详情
(IV)	58258	allyl 2-{(2R,3S)-3-((1R)-1-{[tert-butyl(dimethyl)silyl]oxy}ethyl)-2-[(2-chloroacetyl)sulfanyl]-4-oxoazetidinyl}-2-oxoacetate	C₁₈H₂₈ClNO₆SSi	详情	详情
(V)	58259	allyl (5R,6S)-6-((1R)-1-{[tert-butyl(dimethyl)silyl]oxy}ethyl)-3-(chloromethyl)-7-oxo-4-thia-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylate	C₁₈H₂₈ClNO₄SSi	详情	详情
(VI)	54572	2-(methylamino)acetamide	C₃H₈N₂O	详情	详情
(VII)	58254	allyl (5R,6S)-3-{[(2-amino-2-oxoethyl)(methyl)amino]methyl}-6-((1R)-1-{[tert-butyl(dimethyl)silyl]oxy}ethyl)-7-oxo-4-thia-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylate	C₂₁H₃₅N₃O₅SSi	详情	详情
(VIII)	58255	allyl (5R,6S)-3-{[(2-amino-2-oxoethyl)(methyl)amino]methyl}-6-[(1R)-1-hydroxyethyl]-7-oxo-4-thia-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylate	C₁₅H₂₁N₃O₅S	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 condensation of N-(2-chloroethyl)-N-nitrosocarbamic acid 4-nitrophenyl ester (I) with sarcosinamide (II) gives the target nitrosourea. Alternatively, the nitrosation of N2-[N-(2-chloroethyl)carbamoyl]sarcosinamide (III) by means of NaNO2 and formic acid also yields the target nitrosourea.

参考文献中间体

合成目标

【1】 Suami, T.; et al.; (2-Chloroethyl)nitrosourea congeners of amino acid amides. J Med Chem 1982, 25, 7, 829.
【2】 Suami, T.; Nitrosourea derivs.. US 4452814 .

中间体序号	中间体编号	品名	分子式	供应商	用于合成
(I)	11239	4-nitrophenyl 1-(2-chloroethyl)-2-oxo-1-hydrazinecarboxylate	C₉H₈ClN₃O₅	详情	详情
(II)	54572	2-(methylamino)acetamide	C₃H₈N₂O	详情	详情
(III)	56708	2-[{[(2-chloroethyl)amino]carbonyl}(methyl)amino]acetamide	C₆H₁₂ClN₃O₂	详情	详情

合成路线4

该中间体在本合成路线中的序号：(VI)

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

Extended Information