　 -Drug Synthesis Database

【结构式】

【分子编号】41288

【品名】　

【CA登记号】

【分子式】C₄₆H₅₄N₈O₁₀

【分子量】878.98268

【元素组成】C 62.86% H 6.19% N 12.75% O 18.2%

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：(IV)

The condensation of the cyclopeptide analogue (I) with morpholine (II) and formaldehyde by means of MsOH in hot methanol gives the 4-morpholinylmethyl derivative (III), which by a treatment with NaOAc in hot acetic acid yields the methylene derivative (IV). Finally this compound is condensed with quinuclidine-3(S)-thiol in hot acetone.

参考文献中间体

合成目标

【1】 Bastart, J.P.; Paris, J.M.; Radisson, X. (Aventis SA); Pristinaymcin IA or viginiamycin derivs. and their preparation. EP 0432029 .
【2】 Barriere, J.C.; Paris, J.M.; RP 59500 and related semisynthetic streptogramins. Drugs Fut 1993, 18, 9, 833.

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
(IIIa)	41286			C₅₀H₆₃N₉O₁₁	详情	详情
(IIIb)	41287			C₅₀H₆₃N₉O₁₁	详情	详情
(I)	41285	N-[(6R,9S,10R,13S,15aS,22S,24aS)-22-[4-(dimethylamino)benzyl]-6-ethyl-10,23-dimethyl-5,8,12,15,17,21,24-heptaoxo-13-phenyldocosahydro-12H-pyrido[2,1-f]pyrrolo[2,1-l][1,4,7,10,13,16]oxapentaazacyclononadecin-9-yl]-3-hydroxy-2-pyridinecarboxamide		C₄₅H₅₄N₈O₁₀	详情	详情
(II)	10388	Morpholine	110-91-8	C₄H₉NO	详情	详情
(IV)	41288			C₄₆H₅₄N₈O₁₀	详情	详情
(V)	41289	(3S)-1-azabicyclo[2.2.2]octane-3-thiol; (3S)-1-azabicyclo[2.2.2]oct-3-ylhydrosulfide	4595-82-8	C₇H₁₃NS	详情	详情

合成路线2

该中间体在本合成路线中的序号：(I)

Reduction of the keto group of 5-delta-methylene pristinamycin IA (I) by means of NaBH4 in the presence of CeCl3 provided the allyl alcohol (II). Subsequent chlorination of (II) with SOCl2, furnished a mixture of compounds containing the 5-delta-(chloromethyl) (III) and the 5-gamma-chloro-5-delta-methylene (IV) derivatives. Treatment of the crude mixture with morpholine (V) in refluxing acetonitrile yielded the title 5-delta-morpholinomethyl analogue.

参考文献中间体

合成目标

【1】 Barriere, J.C.; Bacque, E.; Puchault, G.; Dutruc-Rooset, G.; Doerflinger, G.; Berthaud, N.; Design and synthesis of RPR202868, the pristinamycin I component of RPR202868/RPR132552, a new oral streptogramin. 41st Intersci Conf Antimicrob Agents Chemother (Dec 16 2001, Chicago) 2001, Abst F-359.
【2】 Barriere, J.-C.; Pantel, G.; Bacqué, E.; Doerflinger, G.; Dutruc-Rosset, G. (Aventis Pharma SA); Streptogramin derivs., production thereof and compsns. containing the same. EP 1204675; FR 2796949; US 6541451; WO 0110895 .

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)	41288			C₄₆H₅₄N₈O₁₀	详情	详情
(II)	59348	N-{(6R,9S,10R,13S,15aS,22S,24aS)-22-[4-(dimethylamino)benzyl]-6-ethyl-17-hydroxy-10,23-dimethyl-18-methylene-5,8,12,15,21,24-hexaoxo-13-phenyldocosahydro-12H-pyrido[2,1-f]pyrrolo[2,1-l][1,4,7,10,13,16]oxapentaazacyclononadecin-9-yl}-3-hydroxy-2-pyridinecarboxamide		C₄₆H₅₆N₈O₁₀	详情	详情
(III)	59349	N-{(6R,9S,10R,13S,15aS,22S,24aS)-18-(chloromethyl)-22-[4-(dimethylamino)benzyl]-6-ethyl-10,23-dimethyl-5,8,12,15,21,24-hexaoxo-13-phenyl-1,2,3,5,6,7,8,9,10,13,14,15,15a,16,19,21,22,23,24,24a-icosahydro-12H-pyrido[2,1-f]pyrrolo[2,1-l][1,4,7,10,13,16]oxapentaazacyclononadecin-9-yl}-3-hydroxy-2-pyridinecarboxamide		C₄₆H₅₅ClN₈O₉	详情	详情
(IV)	59350	N-{(6R,9S,10R,13S,15aS,22S,24aS)-17-chloro-22-[4-(dimethylamino)benzyl]-6-ethyl-10,23-dimethyl-18-methylene-5,8,12,15,21,24-hexaoxo-13-phenyldocosahydro-12H-pyrido[2,1-f]pyrrolo[2,1-l][1,4,7,10,13,16]oxapentaazacyclononadecin-9-yl}-3-hydroxy-2-pyridinecarboxamide		C₄₆H₅₅ClN₈O₉	详情	详情
(V)	10388	Morpholine	110-91-8	C₄H₉NO	详情	详情

合成路线3

该中间体在本合成路线中的序号：(I)

In an alternative method, Michael addition of morpholine (V) to the unsaturated ketone (I) gave adduct (VI). Subsequent ketone reduction in (VI) with NaBH4 provided the corresponding alcohol (VII) as a diastereomeric mixture. Dehydration of alcohol (VII), upon treatment with diethylaminosulfur trifluoride, then yielded the title compound.

参考文献中间体

合成目标

【1】 Barriere, J.-C.; Pantel, G.; Bacqué, E.; Doerflinger, G.; Dutruc-Rosset, G. (Aventis Pharma SA); Streptogramin derivs., production thereof and compsns. containing the same. EP 1204675; FR 2796949; US 6541451; WO 0110895 .

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)	41288			C₄₆H₅₄N₈O₁₀	详情	详情
(V)	10388	Morpholine	110-91-8	C₄H₉NO	详情	详情
(VI)	59352	N-[(6R,9S,10R,13S,15aS,22S,24aS)-22-[4-(dimethylamino)benzyl]-6-ethyl-10,23-dimethyl-18-(4-morpholinylmethyl)-5,8,12,15,17,21,24-heptaoxo-13-phenyldocosahydro-12H-pyrido[2,1-f]pyrrolo[2,1-l][1,4,7,10,13,16]oxapentaazacyclononadecin-9-yl]-3-hydroxy-2-pyridinecarboxamide		C₅₀H₆₃N₉O₁₁	详情	详情
(VII)	59351	N-[(6R,9S,10R,13S,15aS,22S,24aS)-22-[4-(dimethylamino)benzyl]-6-ethyl-17-hydroxy-10,23-dimethyl-18-(4-morpholinylmethyl)-5,8,12,15,21,24-hexaoxo-13-phenyldocosahydro-12H-pyrido[2,1-f]pyrrolo[2,1-l][1,4,7,10,13,16]oxapentaazacyclononadecin-9-yl]-3-hydroxy-2-pyridinecarboxamide		C₅₀H₆₅N₉O₁₁	详情	详情

Extended Information