|
【结 构 式】 
|
【分子编号】54948 【品名】(7R)-1,4-dioxaspiro[4.5]dec-7-yl[4-phenyl-3,6-dihydro-1(2H)-pyridinyl]methanone 【CA登记号】 |
【 分 子 式 】C20H25NO3 【 分 子 量 】327.42344 【元素组成】C 73.37% H 7.7% N 4.28% O 14.66% |
合成路线1
该中间体在本合成路线中的序号：(XIV)The analogous asymmetric synthesis starting from the (R)-enantiomer of 3-oxocyclohexanecarboxylic acid (XV) was also reported. The chiral (R)-keto acid (XV), prepared by resolution of the racemic acid (XII) with brucine, was coupled with tetrahydropyridine (V) to give keto amide (XVI). Protection as the ethylene ketal (XVII), followed by amide reduction and acidic ketal hydrolysis, furnished the (R)-amino ketone (XVIII). This was converted into the title compound by addition of phenylmagnesium bromide, followed by acidic dehydration and separation of isomers as in Scheme 19758501a.
| 【1】 Wright, J.L.; et al.; The discovery and structure-activity relationships of 1,2,3, 6-tetrahydro-4-phenyl-1-[(arylcyclohexenyl)alkyl]pyridines. Dopamine autoreceptor agonists and potential antipsychotic agents. J Med Chem 1994, 37, 21, 3523. |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (V) | 13002 | 4-Phenyl-1,2,3,6-tetrahydropyridine; 1,2,3,6-Tetrahydro-4-phenyl-pyridine | 10338-69-9 | C11H13N | 详情 | 详情 |
| (XII) | 54943 | 3-oxocyclohexanecarboxylic acid | C7H10O3 | 详情 | 详情 | |
| (XIV) | 54948 | (7R)-1,4-dioxaspiro[4.5]dec-7-yl[4-phenyl-3,6-dihydro-1(2H)-pyridinyl]methanone | C20H25NO3 | 详情 | 详情 | |
| (XV) | 54946 | (1R)-3-oxocyclohexanecarboxylic acid | C7H10O3 | 详情 | 详情 | |
| (XVI) | 54947 | (3R)-3-{[4-phenyl-3,6-dihydro-1(2H)-pyridinyl]carbonyl}cyclohexanone | C18H21NO2 | 详情 | 详情 | |
| (XVII) | 54948 | (7R)-1,4-dioxaspiro[4.5]dec-7-yl[4-phenyl-3,6-dihydro-1(2H)-pyridinyl]methanone | C20H25NO3 | 详情 | 详情 | |
| (XVIII) | 54949 | (3R)-3-{[4-phenyl-3,6-dihydro-1(2H)-pyridinyl]methyl}cyclohexanone | C18H23NO | 详情 | 详情 |
合成路线2
该中间体在本合成路线中的序号：(XVII)The analogous asymmetric synthesis starting from the (R)-enantiomer of 3-oxocyclohexanecarboxylic acid (XV) was also reported. The chiral (R)-keto acid (XV), prepared by resolution of the racemic acid (XII) with brucine, was coupled with tetrahydropyridine (V) to give keto amide (XVI). Protection as the ethylene ketal (XVII), followed by amide reduction and acidic ketal hydrolysis, furnished the (R)-amino ketone (XVIII). This was converted into the title compound by addition of phenylmagnesium bromide, followed by acidic dehydration and separation of isomers as in Scheme 19758501a.
| 【1】 Wright, J.L.; et al.; The discovery and structure-activity relationships of 1,2,3, 6-tetrahydro-4-phenyl-1-[(arylcyclohexenyl)alkyl]pyridines. Dopamine autoreceptor agonists and potential antipsychotic agents. J Med Chem 1994, 37, 21, 3523. |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (V) | 13002 | 4-Phenyl-1,2,3,6-tetrahydropyridine; 1,2,3,6-Tetrahydro-4-phenyl-pyridine | 10338-69-9 | C11H13N | 详情 | 详情 |
| (XII) | 54943 | 3-oxocyclohexanecarboxylic acid | C7H10O3 | 详情 | 详情 | |
| (XIV) | 54948 | (7R)-1,4-dioxaspiro[4.5]dec-7-yl[4-phenyl-3,6-dihydro-1(2H)-pyridinyl]methanone | C20H25NO3 | 详情 | 详情 | |
| (XV) | 54946 | (1R)-3-oxocyclohexanecarboxylic acid | C7H10O3 | 详情 | 详情 | |
| (XVI) | 54947 | (3R)-3-{[4-phenyl-3,6-dihydro-1(2H)-pyridinyl]carbonyl}cyclohexanone | C18H21NO2 | 详情 | 详情 | |
| (XVII) | 54948 | (7R)-1,4-dioxaspiro[4.5]dec-7-yl[4-phenyl-3,6-dihydro-1(2H)-pyridinyl]methanone | C20H25NO3 | 详情 | 详情 | |
| (XVIII) | 54949 | (3R)-3-{[4-phenyl-3,6-dihydro-1(2H)-pyridinyl]methyl}cyclohexanone | C18H23NO | 详情 | 详情 |