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【结 构 式】 
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【分子编号】25112 【品名】2-(1-piperidinyl)benzonitrile 【CA登记号】72752-52-4 |
【 分 子 式 】C12H14N2 【 分 子 量 】186.25664 【元素组成】C 77.38% H 7.58% N 15.04% |
合成路线1
该中间体在本合成路线中的序号：(I)A new synthesis of repaglinide has been described: The reaction of 2-(1-piperidinyl)benzonitrile (I) with isobutylmagnesium bromide (II) in THF followed by hydrolysis with aqueous NH4Cl/NH3 gives 3-methyl-1-[2-(1-piperidinyl)phenyl]butanone (III), which is condensed with 1(S)-phenylethylamine (IV) by means of TiCl4/triethylamine in toluene yielding the imine (V). The hydrogenation of (V) with H2 over Raney Nickel in ethanol affords the chiral secondary amine (IV), which is further hydrogenated with H2 over Pd/C in ethanol/aqueous HCl giving 3-methyl-2(S)-[2-(1-piperidinyl)phenyl]butylamine (VII). The condensation of (VII) with 4-(carboxymethyl)-2-ethoxybenzoic acid ethyl ester (VIII) by means of SOCl2 or carbonyldiimidazole (CDI) or triphenylphosphine/CCl4/triethylamine gives the ethyl ester of repaglinide (IX), which is finally hydrolyzed with NaOH as usual.
| 【1】 Grell, W.; Hurnaus, R.; Griss, G.; Sauter, R.; Rupprecht, E.; Mark, M.; Luger, P.; Nar, H.; Wittneben, H.; Muller, P.; Repaglinide and related hypoglycemic benzoic acid derivatives. J Med Chem 1998, 41, 26, 5219. |
| 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) | 25112 | 2-(1-piperidinyl)benzonitrile | 72752-52-4 | C12H14N2 | 详情 | 详情 |
| (II) | 22876 | bromo(isobutyl)magnesium | 926-62-5 | C4H9BrMg | 详情 | 详情 |
| (III) | 15308 | 3-methyl-1-(2-piperidinophenyl)-1-butanone | C16H23NO | 详情 | 详情 | |
| (IV) | 20042 | (1S)-1-phenyl-1-ethanamine; (1S)-1-phenylethylamine | C8H11N | 详情 | 详情 | |
| (V) | 15311 | N-[(E)-3-methyl-1-(2-piperidinophenyl)butylidene]-N-[(1S)-1-phenylethyl]amine; (1S)-N-[(E)-3-methyl-1-(2-piperidinophenyl)butylidene]-1-phenyl-1-ethanamine | C24H32N2 | 详情 | 详情 | |
| (VI) | 15312 | (1S)-3-methyl-N-[(1S)-1-phenylethyl]-1-(2-piperidinophenyl)-1-butanamine; N-[(1S)-3-methyl-1-(2-piperidinophenyl)butyl]-N-[(1S)-1-phenylethyl]amine | C24H34N2 | 详情 | 详情 | |
| (VII) | 15315 | (1S)-3-methyl-1-(2-piperidinophenyl)butylamine; (1S)-3-methyl-1-(2-piperidinophenyl)-1-butanamine | C16H26N2 | 详情 | 详情 | |
| (VIII) | 15301 | 2-[3-ethoxy-4-(ethoxycarbonyl)phenyl]acetic acid | C13H16O5 | 详情 | 详情 | |
| (IX) | 15316 | ethyl 2-ethoxy-4-(2-[[(1S)-3-methyl-1-(2-piperidinophenyl)butyl]amino]-2-oxoethyl)benzoate | C29H40N2O4 | 详情 | 详情 |