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【结 构 式】 
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【分子编号】62010 【品名】dimethyl (E)-2-phenoxy-2-butenedioate 【CA登记号】 |
【 分 子 式 】C12H12O5 【 分 子 量 】236.22428 【元素组成】C 61.01% H 5.12% O 33.86% |
合成路线1
该中间体在本合成路线中的序号：(III)The reaction of uniformly 14C-labeled phenol (I) with acetylenedicarboxylic acid dimethyl ester (II) gives the adduct (III), which is reduced with ammonium formate and Pd/C to yield the 2-phenoxysuccinic acid dimethyl ester (IV). The hydrolysis of (IV) in acidic medium (HCl) affords the succinic acid derivative (V), which is cyclized by means of P2O5 to provide 4-oxo-3,4-dihydro-2H-1-benzopyran-2-carboxylic acid (VI). The reduction of (VI) by means of Ph3SiH and TFA gives 3,4-dihydro-2H-1-benzopyran-2-carboxylic acid (VII), which is condensed with 1(R)-phenylethylamine (VIII) by means of CDI to yield the corresponding amide (IX) as a diastereomeric mixture. The reduction of (IX) by means of NaAlH2(OC2H4OMe)2 affords the secondary amine (X), also as a diastereomeric mixture, which is resolved by chromatography. The desired isomer (XI) is condensed with the butyl bromide derivative (XII) by means of NaHCO3 and KI to provide the tertiary amine (XIII), which is finally debenzylated by hydrogenation with H2 over Pd/C to furnish the target labeled Repinotan.
| 【1】 Seidel, D.; et al.; Synthesis of [14C]-labelled repinotan hydrochloride and its major metabolite M-6. J Label Compd Radiopharm 2002, 45, 13, 1115. |
| 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) | 23540 | Phenol | 108-95-2 | C6H6O | 详情 | 详情 |
| (II) | 24551 | Dimethyl acetylenedicarboxylate; Dimethyl 2-butynedioate;Acetylenedicarboxylic acid dimethyl ester | 762-42-5 | C6H6O4 | 详情 | 详情 |
| (III) | 62010 | dimethyl (E)-2-phenoxy-2-butenedioate | C12H12O5 | 详情 | 详情 | |
| (IV) | 62011 | dimethyl 2-phenoxysuccinate | C12H14O5 | 详情 | 详情 | |
| (V) | 62012 | 2-phenoxysuccinic acid | C10H10O5 | 详情 | 详情 | |
| (VI) | 62013 | 4-oxo-2-chromanecarboxylic acid | C10H8O4 | 详情 | 详情 | |
| (VII) | 17037 | 2-chromanecarboxylic acid | C10H10O3 | 详情 | 详情 | |
| (VIII) | 10039 | (1R)-1-Phenylethylamine; (1R)-1-Phenyl-1-ethanamine.; L-alpha-Phenylethylamine | 3886-69-9 | C8H11N | 详情 | 详情 |
| (IX) | 17040 | (2R)-N-[(1S)-1-phenylethyl]-3,4-dihydro-2H-chromene-2-carboxamide | C18H19NO2 | 详情 | 详情 | |
| (X) | 17041 | (1S)-N-[(2R)-3,4-dihydro-2H-chromen-2-ylmethyl]-1-phenyl-1-ethanamine; N-[(2R)-3,4-dihydro-2H-chromen-2-ylmethyl]-N-[(1S)-1-phenylethyl]amine | C18H21NO | 详情 | 详情 | |
| (XI) | 62014 | (1R)-N-[(2R)-3,4-dihydro-2H-chromen-2-ylmethyl]-1-phenyl-1-ethanamine; N-[(2R)-3,4-dihydro-2H-chromen-2-ylmethyl]-N-[(1R)-1-phenylethyl]amine | C18H21NO | 详情 | 详情 | |
| (XII) | 17043 | 2-(4-bromobutyl)-1H-1,2-benzisothiazole-1,1,3(2H)-trione | C11H12BrNO3S | 详情 | 详情 | |
| (XIII) | 62015 | 2-(4-{[(2R)-3,4-dihydro-2H-chromen-2-ylmethyl][(1R)-1-phenylethyl]amino}butyl)-1H-1,2-benzisothiazole-1,1,3(2H)-trione | C29H32N2O4S | 详情 | 详情 |