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【结 构 式】

【分子编号】33915

【品名】(2R)-2-[(1S,2S,6R,14R,15S,16R)-5-cyano-11,15-dimethoxy-13-oxa-5-azahexacyclo[13.2.2.1(2,8).0(1,6).0(2,14).0(12,20)]icosa-8(20),9,11-trien-16-yl]-3,3-dimethyl-2-butanol

【CA登记号】

【 分 子 式 】C27H36N2O4

【 分 子 量 】452.59392

【元素组成】C 71.65% H 8.02% N 6.19% O 14.14%

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:(IV)

The hydrogenation of 7-acetyl-6,14-endoetheno-6,7,8,14-tetrahydrothebaine (I) with H2 over Pd/C in acetic acid gives the corresponding endo-ethano derivative (II), which by a Grignard reaction with tertbutyl-magnesium chloride (A) in ether-benzene yields 7alpha-(2-hydroxy-3,3-dimethyl-2-butyl)-6,14-endo-ethano-6,7,8,14-tetrahydrothebaine (III). The reaction of III with BrCN in CH2Cl2 affords 7alpha-(2-hydroxy-3,3-dimethyl-2-butyl)-6,14-endo-ethano-N-cyano-6,7,8,14-tetrahydronorthebaine (IV), which is treated with KOH in ethylene glycol at 170 C to give 7alpha(2-hydroxy-3,3-dimethyl-2-butyl)-6,14-endo-ethano-6,7,8,14-tetrahydronorthebaine (V). This compound is treated first with cyclopropylcarbonyl chloride (B) in CH2Cl2 containing triethylamine, followed by a reduction with LiAlH4 in refluxing THF yielding N-cyclopropylmethyl-7alpha-(2-hydroxy-3,3-dimethyl-2-butyl)-6,14-endo-ethano-6,7,8,14-tetrahydro-northebaine (VI). Finally, (VI) is demethylated with KOH in diethylene glycol at 210-220 C.

1 Bentley, K.W.; Thebaine and Oripavine derivatives. CH 558362; DE 1620206; FR 6395M; GB 1136214 .
2 Castaner, J.; Paton, D.M.; Buprenorphine. Drugs Fut 1977, 2, 9, 570.
中间体序号 中间体编号 品名 CAS号 分子式 供应商 用于合成
(B) 14061 Cyclopropanecarbonyl chloride; Cyclopropanecarboxylic acid chloride 4023-34-1 C4H5ClO 详情 详情
(A) 15459 tert-butyl(chloro)magnesium 677-22-5 C4H9ClMg 详情 详情
(I) 33912 1-[(1R,2S,6R,14R,15S,16S)-11,15-dimethoxy-5-methyl-13-oxa-5-azahexacyclo[13.2.2.1(2,8).0(1,6).0(2,14).0(12,20)]icosa-8(20),9,11,18-tetraen-16-yl]-1-ethanone C23H27NO4 详情 详情
(II) 33913 1-[(1S,2S,6R,14R,15S,16S)-11,15-dimethoxy-5-methyl-13-oxa-5-azahexacyclo[13.2.2.1(2,8).0(1,6).0(2,14).0(12,20)]icosa-8(20),9,11-trien-16-yl]-1-ethanone C23H29NO4 详情 详情
(III) 33914 (2R)-2-[(1S,2S,6R,14R,15S,16R)-11,15-dimethoxy-5-methyl-13-oxa-5-azahexacyclo[13.2.2.1(2,8).0(1,6).0(2,14).0(12,20)]icosa-8(20),9,11-trien-16-yl]-3,3-dimethyl-2-butanol C27H39NO4 详情 详情
(IV) 33915 (2R)-2-[(1S,2S,6R,14R,15S,16R)-5-cyano-11,15-dimethoxy-13-oxa-5-azahexacyclo[13.2.2.1(2,8).0(1,6).0(2,14).0(12,20)]icosa-8(20),9,11-trien-16-yl]-3,3-dimethyl-2-butanol C27H36N2O4 详情 详情
(V) 33916 (2R)-2-[(1S,2S,6R,14R,15S,16R)-11,15-dimethoxy-13-oxa-5-azahexacyclo[13.2.2.1(2,8).0(1,6).0(2,14).0(12,20)]icosa-8(20),9,11-trien-16-yl]-3,3-dimethyl-2-butanol C26H37NO4 详情 详情
(VI) 33917 (2R)-2-[(1S,2S,6R,14R,15S,16R)-5-(cyclopropylmethyl)-11,15-dimethoxy-13-oxa-5-azahexacyclo[13.2.2.1(2,8).0(1,6).0(2,14).0(12,20)]icosa-8(20),9,11-trien-16-yl]-3,3-dimethyl-2-butanol C30H43NO4 详情 详情
Extended Information