(4S,4aS,5aR,12aS)-9-[(2-bromoacetyl)amino]-4,7-bis(dimethylamino)-3,10,12,12a-tetrahydroxy-1,11-dioxo-1,4,4a,5,5a,6,11,12a-octahydro-2-naphthacenecarboxamide -Drug Synthesis Database

【结构式】

【分子编号】48570

【品名】(4S,4aS,5aR,12aS)-9-[(2-bromoacetyl)amino]-4,7-bis(dimethylamino)-3,10,12,12a-tetrahydroxy-1,11-dioxo-1,4,4a,5,5a,6,11,12a-octahydro-2-naphthacenecarboxamide

【CA登记号】

【分子式】C₂₅H₂₉BrN₄O₈

【分子量】593.43142

【元素组成】C 50.6% H 4.93% Br 13.46% N 9.44% O 21.57%

与该中间体有关的原料药合成路线共 1 条

合成路线1

该中间体在本合成路线中的序号：(V)

Nitration of minocycline (I) with KNO3 and H2SO4 gives the 9-nitro derivative (II), which is reduced with H2 over Pd/C in 2-methoxyethanol/2N H2SO4 to provide 9-aminominocycline (III). Acylation of compound (III) with 2-bromoacetyl bromide (IV) in N,N-dimethylpropyleneurea (DMPU) affords 9-(2-bromoacetamido)minocycline (V). Finally, this compound is treated with tert-butylamine (VI) to yield, after purification, GAR-936.

参考文献中间体

合成目标

【1】 Hunter, P.A.; Castaner, J.; GAR-936. Drugs Fut 2001, 26, 9, 851.
【2】 Sum, P.-E.; Petersen, P.; Synthesis and structure-activity relationship of novel glycylcline derivatives leading to the discovery of GAR-936. Bioorg Med Chem Lett 1999, 9, 10, 1459.
【3】 Sum, P.-E.; Lee, V.J. (American Cyanamid Co.); Method of producing 7-(substd.)-9-[(substd. glycyl)amidol]-6-demethyl-6-deoxytetracyclines. EP 0582790; US 5284963 .
【4】 Sum, P.-E.; Lee, V.J.; Testa, R.T.; Hlavka, J.J.; Ellestad, G.A.; Bloom, J.D.; Gluzman, Y.; Tally, F.P.; Glycylcyclines. 1. A new generation of potent antibacterial agents through modification of 9-aminotetracyclines. J Med Chem 1994, 37, 1, 184-8.

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)	16360	(4S,4aS,5aR,12aS)-4,7-bis(dimethylamino)-3,10,12,12a-tetrahydroxy-1,11-dioxo-1,4,4a,5,5a,6,11,12a-octahydro-2-naphthacenecarboxamide	10118-90-8	C₂₃H₂₇N₃O₇	详情	详情
(II)	16361	(4S,4aS,5aR,12aS)-4,7-bis(dimethylamino)-3,10,12,12a-tetrahydroxy-9-nitro-1,11-dioxo-1,4,4a,5,5a,6,11,12a-octahydro-2-naphthacenecarboxamide		C₂₃H₂₆N₄O₉	详情	详情
(III)	16362	(4S,4aS,5aR,12aS)-9-amino-4,7-bis(dimethylamino)-3,10,12,12a-tetrahydroxy-1,11-dioxo-1,4,4a,5,5a,6,11,12a-octahydro-2-naphthacenecarboxamide		C₂₃H₂₈N₄O₇	详情	详情
(IV)	14005	2-Bromoacetyl bromide; Bromoacetyl bromide	598-21-0	C₂H₂Br₂O	详情	详情
(V)	48570	(4S,4aS,5aR,12aS)-9-[(2-bromoacetyl)amino]-4,7-bis(dimethylamino)-3,10,12,12a-tetrahydroxy-1,11-dioxo-1,4,4a,5,5a,6,11,12a-octahydro-2-naphthacenecarboxamide		C₂₅H₂₉BrN₄O₈	详情	详情
(VI)	17895	2-Amino-2-methylpropane; tert-butylamine; 2-methyl-2-propanamine	75-64-9	C₄H₁₁N	详情	详情
(VII)	48571	2-(tert-butylamino)acetyl chloride		C₆H₁₂ClNO	详情	详情

Extended Information