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【结 构 式】 
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【分子编号】23689 【品名】2,2-dimethyl-5-propionyl-1,3-dioxane-4,6-dione 【CA登记号】 |
【 分 子 式 】C9H12O5 【 分 子 量 】200.19128 【元素组成】C 54% H 6.04% O 39.96% |
合成路线1
该中间体在本合成路线中的序号：(III)Acylation of Meldrum's acid (I) with propionyl chloride (II) in the presence of pyridine gave propionyl derivative (III). Subsequent ring opening of (III) with ethanethiol (IV), followed by decarboxylation provided S-ethyl 3-oxothiovalerate (V). Propyl 3-amino-3-phenyl-2-propenoate (VII) was prepared by reaction of benzoylacetate (VI) with ammonium acetate in refluxing ethanol. Then, Hantzsch condensation of ketothioester (V), beta-enaminoester (VII), and butyraldehyde (VIII) in EtOH at 80 C in a sealed tube furnished the dihydropyridine (IX). Finally, oxidation of (IX) using chloranil (X) in boiling THF gave the target pyridine.
| 【1】 Li, A.-H.; Moro, S.; Melman, N.; Ji, X.D.; Jacobson, K.A.; Structure-activity relationships and molecular mod. J Med Chem 1998, 41, 17, 3186. |
| 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) | 21391 | D-aspartic acid; (2R)-2-aminobutanedioic acid | 1783-96-6 | C4H7NO4 | 详情 | 详情 |
| (I) | 14738 | Meldrum's acid; 2,2-dimethyl-1,3-dioxane-4,6-dione；Malonic acid cyclic isopropylidene ester | 2033-24-1 | C6H8O4 | 详情 | 详情 |
| (II) | 15967 | propanoyl chloride; propionyl chloride | 79-03-8 | C3H5ClO | 详情 | 详情 |
| (III) | 23689 | 2,2-dimethyl-5-propionyl-1,3-dioxane-4,6-dione | C9H12O5 | 详情 | 详情 | |
| (IV) | 23712 | 1-ethanethiol; ethylhydrosulfide | 75-08-1 | C2H6S | 详情 | 详情 |
| (V) | 23696 | S-ethyl 3-oxopentanethioate | C7H12O2S | 详情 | 详情 | |
| (VI) | 23692 | propyl 3-oxo-3-phenylpropanoate | C12H14O3 | 详情 | 详情 | |
| (VII) | 23693 | propyl (E)-3-amino-3-phenyl-2-propenoate | C12H15NO2 | 详情 | 详情 | |
| (VIII) | 23694 | butyraldehyde | 123-72-8 | C4H8O | 详情 | 详情 |
| (IX) | 23695 | propyl 6-ethyl-5-[(ethylsulfanyl)carbonyl]-2-phenyl-4-propyl-1,4-dihydro-3-pyridinecarboxylate | C23H31NO3S | 详情 | 详情 |
合成路线2
该中间体在本合成路线中的序号：(III)Acylation of Meldrum's acid (I) with propionyl chloride (II) in the presence of pyridine gave propionyl derivative (III). Subsequent ring opening of (III) with ethanethiol (IV), followed by decarboxylation provided S-ethyl 3-oxothiovalerate (V). Ethyl 3-amino-3-phenyl-2-propenoate (VII) was prepared by reaction of benzoylacetate (VI) with ammonium acetate in refluxing ethanol. Then, Hantzsch condensation of ketothioester (V), beta-enaminoester (VII), and propionaldehyde (VIII) in EtOH at 80 C in a sealed tube furnished the dihydropyridine (IX). Finally, oxidation of (IX) using chloranil (X) in boiling THF gave the target pyridine.
| 【1】 Li, A.-H.; Moro, S.; Melman, N.; Ji, X.D.; Jacobson, K.A.; Structure-activity relationships and molecular mod. J Med Chem 1998, 41, 17, 3186. |
| 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) | 14738 | Meldrum's acid; 2,2-dimethyl-1,3-dioxane-4,6-dione；Malonic acid cyclic isopropylidene ester | 2033-24-1 | C6H8O4 | 详情 | 详情 |
| (II) | 15967 | propanoyl chloride; propionyl chloride | 79-03-8 | C3H5ClO | 详情 | 详情 |
| (III) | 23689 | 2,2-dimethyl-5-propionyl-1,3-dioxane-4,6-dione | C9H12O5 | 详情 | 详情 | |
| (IV) | 23712 | 1-ethanethiol; ethylhydrosulfide | 75-08-1 | C2H6S | 详情 | 详情 |
| (V) | 23696 | S-ethyl 3-oxopentanethioate | C7H12O2S | 详情 | 详情 | |
| (VI) | 23692 | propyl 3-oxo-3-phenylpropanoate | C12H14O3 | 详情 | 详情 | |
| (VII) | 23693 | propyl (E)-3-amino-3-phenyl-2-propenoate | C12H15NO2 | 详情 | 详情 | |
| (VIII) | 15966 | propionaldehyde | 123-38-6 | C3H6O | 详情 | 详情 |
| (IX) | 23699 | ethyl 4,6-diethyl-5-[(ethylsulfanyl)carbonyl]-2-phenyl-1,4-dihydro-3-pyridinecarboxylate | C21H27NO3S | 详情 | 详情 | |
| (X) | 21891 | 2,3,5,6-Tetrachloro-1,4-benzoquinone; 2,3,5,6-Tetrachlorobenzo-1,4-quinone; p-Chloranil | 118-75-2 | C6Cl4O2 | 详情 | 详情 |
合成路线3
该中间体在本合成路线中的序号：(III)Acylation of Meldrum's acid (I) with propionyl chloride (II) in the presence of pyridine gave propionyl derivative (III). Subsequent ring opening of (III) with propanethiol (IV), followed by decarboxylation provided S-propyl 3-oxothiovalerate (V). Propyl 3-amino-3-(m-chlorophenyl)-2-propenoate (VII) was prepared by reaction of (3-chlorobenzoyl)acetate (VI) with ammonium acetate in refluxing ethanol. Then, Hantzsch condensation of ketothioester (V), beta-enaminoester (VII), and propionaldehyde (VIII) in EtOH at 80 C in a sealed tube furnished the dihydropyridine (IX). Finally, oxidation of (IX) using chloranil (X) in boiling THF gave the target pyridine.
| 【1】 Li, A.-H.; Moro, S.; Melman, N.; Ji, X.D.; Jacobson, K.A.; Structure-activity relationships and molecular mod. J Med Chem 1998, 41, 17, 3186. |
| 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) | 14738 | Meldrum's acid; 2,2-dimethyl-1,3-dioxane-4,6-dione；Malonic acid cyclic isopropylidene ester | 2033-24-1 | C6H8O4 | 详情 | 详情 |
| (II) | 15967 | propanoyl chloride; propionyl chloride | 79-03-8 | C3H5ClO | 详情 | 详情 |
| (III) | 23689 | 2,2-dimethyl-5-propionyl-1,3-dioxane-4,6-dione | C9H12O5 | 详情 | 详情 | |
| (IV) | 23703 | propylhydrosulfide; 1-propanethiol | 107-03-9 | C3H8S | 详情 | 详情 |
| (V) | 23704 | S-propyl 3-oxopentanethioate | C8H14O2S | 详情 | 详情 | |
| (VI) | 23705 | propyl 3-(3-chlorophenyl)-3-oxopropanoate | C12H13ClO3 | 详情 | 详情 | |
| (VII) | 23706 | propyl (E)-3-amino-3-(3-chlorophenyl)-2-propenoate | C12H14ClNO2 | 详情 | 详情 | |
| (VIII) | 15966 | propionaldehyde | 123-38-6 | C3H6O | 详情 | 详情 |
| (IX) | 23708 | propyl 2-(3-chlorophenyl)-4,6-diethyl-5-[(propylsulfanyl)carbonyl]-1,4-dihydro-3-pyridinecarboxylate | C23H30ClNO3S | 详情 | 详情 | |
| (X) | 21891 | 2,3,5,6-Tetrachloro-1,4-benzoquinone; 2,3,5,6-Tetrachlorobenzo-1,4-quinone; p-Chloranil | 118-75-2 | C6Cl4O2 | 详情 | 详情 |