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【结 构 式】 
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【分子编号】12110 【品名】3-[Benzyl(methyl)amino]-2,2-dimethyl-1-propanol 【CA登记号】 |
【 分 子 式 】C13H21NO 【 分 子 量 】207.31588 【元素组成】C 75.32% H 10.21% N 6.76% O 7.72% |
合成路线1
该中间体在本合成路线中的序号：(V)A new synthesis for TC-81 has been described: By condensation of 2-(2-fluoro-5-nitrobenzylidene)acetoacetic acid methyl ester (I) with 3-aminocrotonic acid 3-(N-benzyl-N-methylamino)-2,2-dimethylpropyl ester (II) by means of triethylamine in refluxing isopropanol. The starting products (I) and (II) are prepared as follows: The condensation of 2-fluoro-5-nitrobenzaldehyde (III) with methylacetoacetate (IV) by means of HCl in toluene gives the benzylidene derivative (I). The condensation of 3-(N-benzyl-N-methylamino)-2,2-dimethylpropanol (V) with diketene (VI) in hot benzene gives the acetoacetic ester (VII), which is treated with gaseous ammonia in ethanol, yielding crotonate (III).
| 【1】 Okamiya, Y.; Yamaguchi, H.; Takeshita, T.; Sunakawa, K.; Kanno, H.; Synthesis and antihypertensive activity of 1,4-dihydropyridine derivatives with a 4-(disubstituted phenyl)ring and an aminoalkyl ester group: Highly potent and long-lasting calcium antagonists. Chem Pharm Bull 1992, 40, 8, 2049. |
| 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) | 12106 | methyl (Z)-2-acetyl-3-(2-fluoro-5-nitrophenyl)-2-propenoate | C12H10FNO5 | 详情 | 详情 | |
| (II) | 12107 | 3-[benzyl(methyl)amino]-2,2-dimethylpropyl (E)-3-amino-2-butenoate | C17H26N2O2 | 详情 | 详情 | |
| (III) | 12108 | 2-Fluoro-5-nitrobenzaldehyde | 27996-87-8 | C7H4FNO3 | 详情 | 详情 |
| (IV) | 11791 | methyl 3-oxobutanoate; Methyl acetoacetate | 105-45-3 | C5H8O3 | 详情 | 详情 |
| (V) | 12110 | 3-[Benzyl(methyl)amino]-2,2-dimethyl-1-propanol | C13H21NO | 详情 | 详情 | |
| (VI) | 11367 | 4-Methylene-2-oxetanone; Acetyl ketene | 674-82-8 | C4H4O2 | 详情 | 详情 |
| (VII) | 12112 | 3-[benzyl(methyl)amino]-2,2-dimethylpropyl 3-oxobutanoate | C17H25NO3 | 详情 | 详情 |
合成路线2
该中间体在本合成路线中的序号：(IV)1) The reaction of N-methyl-N-benzylamine (I) with isobutyraldehyde (II) and formaldehyde (III) in refluxing isopropanol, followed by hydrogenation with NaBH4 gives 3-(N-benzyl-N-methylamino)-2,2-dimethylpropanol (IV), which is condensed with diketene (V) in refluxing benzene to yield 3-(N-benzyl-N-methylamino)-2,2-dimethylpropyl acetoacetate (VI). Finally, this compound is submitted to cyclization with 2-fluoro-5-nitrobenzeldehyde (VII) (prepared by oxidation of 2-fluoro-5-nitrotoluene (VIII) with CrO3 in acetic ahydride-H2SO4) and methyl 3-aminocrotonate (IX) in refluxing isopropanol.
| 【1】 Yamaguchi, H.; Odamiya, Y.; Kanno, H.; Sunakawa, K. (Teijin Ltd.); 1,4-Dihydropyridine derivs., process for production thereof and pharmaceutical use thereof. EP 0128010; JP 1984222474; JP 1984227859; JP 1985104065; US 4578395 . |
| 【2】 Prous, J.; Castaner, J.; TC-81. Drugs Fut 1989, 14, 3, 239. |
| 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) | 11969 | N-Methyl(phenyl)methanamine; N-Benzyl-N-methylamine; N-Methylbenzylamine | 103-67-3 | C8H11N | 详情 | 详情 |
| (II) | 13226 | 2-Methylpropanal; Isobutyraldehyde | 78-84-2 | C4H8O | 详情 | 详情 |
| (IV) | 12110 | 3-[Benzyl(methyl)amino]-2,2-dimethyl-1-propanol | C13H21NO | 详情 | 详情 | |
| (V) | 11367 | 4-Methylene-2-oxetanone; Acetyl ketene | 674-82-8 | C4H4O2 | 详情 | 详情 |
| (VI) | 12112 | 3-[benzyl(methyl)amino]-2,2-dimethylpropyl 3-oxobutanoate | C17H25NO3 | 详情 | 详情 | |
| (VII) | 12108 | 2-Fluoro-5-nitrobenzaldehyde | 27996-87-8 | C7H4FNO3 | 详情 | 详情 |
| (VIII) | 20560 | 1-fluoro-2-methyl-4-nitrobenzene | 455-88-9 | C7H6FNO2 | 详情 | 详情 |
| (IX) | 11372 | Methyl (E)-3-amino-2-butenoate; Methyl 3-aminocrotonate | C5H9NO2 | 详情 | 详情 |