|
【结 构 式】 
|
【分子编号】50974 【品名】(1S,2S,13R,21R)-14-oxa-11,22-diazaheptacyclo[13.9.1.0(1,13).0(2,21).0(4,12).0(5,10).0(19,25)]pentacosa-4(12),5,7,9,15(25),16,18-heptaene-2,16-diol 【CA登记号】 |
【 分 子 式 】C22H20N2O3 【 分 子 量 】360.41248 【元素组成】C 73.32% H 5.59% N 7.77% O 13.32% |
合成路线1
该中间体在本合成路线中的序号：(III)Noroxymorphindole (III) was prepared by Fischer indole synthesis from noroxymorphone (I) and phenylhydrazine (II) under acidic conditions. Alkylation of (III) with 2-methyl-2-propenyl bromide (IV) in the presence of NaHCO3 in DMF afforded the title compound.
| 【1】 McLamore, S.; et al.; Effect of N-alkyl and N-alkenyl substituents in noroxymorphindole, 17-substituted-6,7-dehydro-4,5alpha-epoxy-3,14-dihydroxy-6,7:2',3'-indolomorphinans on opioid receptor affinity, selectivity, and efficacy. J Med Chem 2001, 44, 9, 1471. |
| 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) | 33927 | (1S,5R,13R,17S)-10,17-dihydroxy-12-oxa-4-azapentacyclo[9.6.1.0(1,13).0(5,17).0(7,18)]octadeca-7(18),8,10-trien-14-one | C16H17NO4 | 详情 | 详情 | |
| (II) | 11818 | Phenyl hydrazine; 1-Phenylhydrazine | 100-63-0 | C6H8N2 | 详情 | 详情 |
| (III) | 50974 | (1S,2S,13R,21R)-14-oxa-11,22-diazaheptacyclo[13.9.1.0(1,13).0(2,21).0(4,12).0(5,10).0(19,25)]pentacosa-4(12),5,7,9,15(25),16,18-heptaene-2,16-diol | C22H20N2O3 | 详情 | 详情 | |
| (IV) | 40015 | 3-bromo-2-methyl-1-propene | 1458-98-6 | C4H7Br | 详情 | 详情 |
合成路线2
该中间体在本合成路线中的序号：(VIII)Condensation of 16-alpha-bromo-3-beta-hydroxy-5-androsten-17-one (I) with piperidine (II) produced the 16-piperidino derivative (III). Oppenauer oxidation of alcohol (III) with concomitant double-bond migration afforded the unsaturated ketone (IV), which was subsequently condensed with pyrrolidine (V) to yield the dienamine (VI). Reduction of the enamine and ketone functions of (VI) with NaBH4 gave the pyrrolidino alcohol (VII). This was then esterified with acetic anhydride in hot pyridine, yielding acetate (VIII). Finally, quaternization of (VIII) with methyl iodide provided the title bis-ammonium salt.
| 【1】 Fajrak, H.; Piplani, P.; Marshall, I.G.; Prior, C.; Jindal, D.P.; Synthesis and neuromuscular blocking activity of 16beta-piperidinosteroidal derivatives. Eur J Med Chem 2001, 36, 2, 195. |
| 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) | 30080 | (3S,8R,9S,10R,13S,14S,16R)-16-bromo-3-hydroxy-10,13-dimethyl-1,2,3,4,7,8,9,10,11,12,13,14,15,16-tetradecahydro-17H-cyclopenta[a]phenanthren-17-one | C19H27BrO2 | 详情 | 详情 | |
| (II) | 10158 | Piperidine | 110-89-4 | C5H11N | 详情 | 详情 |
| (III) | 50970 | (3S,8R,9S,10R,13S,14S,16S)-3-hydroxy-10,13-dimethyl-16-(1-piperidinyl)-1,2,3,4,7,8,9,10,11,12,13,14,15,16-tetradecahydro-17H-cyclopenta[a]phenanthren-17-one | C24H37NO2 | 详情 | 详情 | |
| (IV) | 50971 | (8R,9S,10R,13S,14S,16S)-10,13-dimethyl-16-(1-piperidinyl)-3-(1-pyrrolidinyl)-1,2,7,8,9,10,11,12,13,14,15,16-dodecahydro-17H-cyclopenta[a]phenanthren-17-one | C28H42N2O | 详情 | 详情 | |
| (V) | 11376 | Pyrrolidine | 123-75-1 | C4H9N | 详情 | 详情 |
| (VI) | 50972 | (3S,8R,9S,10R,13S,14S,16S,17R)-10,13-dimethyl-16-(1-piperidinyl)-3-(1-pyrrolidinyl)-2,3,4,7,8,9,10,11,12,13,14,15,16,17-tetradecahydro-1H-cyclopenta[a]phenanthren-17-ol | C28H46N2O | 详情 | 详情 | |
| (VII) | 50973 | (3S,8R,9S,10R,13S,14S,16S,17R)-10,13-dimethyl-16-(1-piperidinyl)-3-(1-pyrrolidinyl)-2,3,4,7,8,9,10,11,12,13,14,15,16,17-tetradecahydro-1H-cyclopenta[a]phenanthren-17-yl acetate | C30H48N2O2 | 详情 | 详情 | |
| (VIII) | 50974 | (1S,2S,13R,21R)-14-oxa-11,22-diazaheptacyclo[13.9.1.0(1,13).0(2,21).0(4,12).0(5,10).0(19,25)]pentacosa-4(12),5,7,9,15(25),16,18-heptaene-2,16-diol | C22H20N2O3 | 详情 | 详情 |