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【结 构 式】 
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【分子编号】44623 【品名】 【CA登记号】 |
【 分 子 式 】C7H6O2 【 分 子 量 】122.12344 【元素组成】C 68.85% H 4.95% O 26.2% |
合成路线1
该中间体在本合成路线中的序号：(II)A new synthesis of 13C- or 14C-labeled SKF-86466 has been described: The Friedel Craft's condensation of labeled benzene (I) with oxalyl chloride by means of AlCl3 in CS2 yields benzoic acid (II), which is chlorinated by means of cupric chloride and thallium (III) trifluoroacetate in trifluoroacetic acid to give 2-chlorobenzoic acid (III). The reduction of (III) by means of borane/THF complex in THF affords 2-chlorobenzyl alcohol (IV), which is treated with hot concentrated HCl to afford 2-chlorobenzyl chloride (V). The Grignard condensation of (V) with N-methyloxazolidine (VI) by means of Mg in ether gives N-[2-(2-chlorophenyl)ethyl]-N-methyl-2-hydroxyethylamine (VII), which is finally cyclized by treatment with PCl5 in hot trichlorobenzene followed by addition of AlCl3 and heating at 215-25 C.
| 【1】 Etzkorn, F.; Villani, A.J.; Rotert, G.A.; Heys, J.R.; Synthesis of 13C, 14C and 2H13C labeled adrenoceptor antagonists: 6-c hloro-2,3,4,5-tetrahydro-3-methyl-1H-3-benzazepine hydrochloride and its N-desmethyl analog. J Label Compd Radiopharm 1988, 25, 12, 1339. |
| 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) | 13364 | Benzene | 71-43-2 | C6H6 | 详情 | 详情 |
| (I) | 44622 | C6H6 | 详情 | 详情 | ||
| (II) | 10202 | Benzoic acid | 65-85-0 | C7H6O2 | 详情 | 详情 |
| (II) | 44623 | C7H6O2 | 详情 | 详情 | ||
| (III) | 10203 | o-Chlorobenzoic acid; 2-Chlorobenzoic acid | 118-91-2 | C7H5ClO2 | 详情 | 详情 |
| (III) | 44624 | C7H5ClO2 | 详情 | 详情 | ||
| (IV) | 10204 | 2-Chlorobenzyl alcohol; (2-Chlorophenyl)methanol | 17849-38-6 | C7H7ClO | 详情 | 详情 |
| (IV) | 44625 | C7H7ClO | 详情 | 详情 | ||
| (V) | 10205 | 1-Chloro-2-(chloromethyl)benzene; 2-Chlorobenzyl chloride | 611-19-8 | C7H6Cl2 | 详情 | 详情 |
| (V) | 44626 | C7H6Cl2 | 详情 | 详情 | ||
| (VI) | 10206 | 3-Methyl-1,3-oxazolane | C4H9NO | 详情 | 详情 | |
| (VII) | 10207 | 2-[(2-Chlorophenethyl)(methyl)amino]-1-ethanol | C11H16ClNO | 详情 | 详情 | |
| (VII) | 44627 | C11H16ClNO | 详情 | 详情 |
合成路线2
该中间体在本合成路线中的序号：(I)The reaction of [benzene-U-13C]benzoic acid (I) with SOCl2 gives the corresponding acyl chloride (II), which is cyclized with the ethanolamine (III) to yield the oxazoline (IV).The chlorination of (IV) with sec-BuLi and hexachloroethane in toluene affords the 2-chlorophenyl derivative (V), which is methylated with MeI to provide the oxazolinium salt (VI). The reduction of (VI) with NaBH4 in ethanol yields the oxazolidine (VII), which is hydrolyzed with HCl to afford the labeled 2-chlorobenzaldehyde (VIII). The condensation of aldehyde (VIII) with the tetrahydrothienopyridine (IX) by means of acetone cyanohydrine in hot toluene affords the substituted acetonitrile (X), which is hydrolyzed to the substituted acetamide (XI) with HCl in methanol. Finally, this compound is treated with H2SO4 in refluxing methanol to afford the target labeled methyl ester as a racemic mixture.
| 【1】 Kashimura, S.; Kuwata, F.; Ishige, O.; Uyama, H.; Shono, T.; Yamaguchi, Y.; Formation of a novel acyl anion equivalent by the electroreduction of oxazolinium salts. Chem Lett 1987, 1511. |
| 【2】 Burgos, A.; Simpson, I.; Herbert, J.M.; Ortho-metalation/chlorination of benzoic acid derivatives: Preparation of [benzene-U-C-13]-rac-clopidogrel ([benzene-U-C-13]-rac-SR25990C). J Label Compd Radiopharm 2000, 43, 9, 891. |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| 63476 | methyl 2-(2-chlorophenyl)-2-[6,7-dihydrothieno[3,2-c]pyridin-5(4H)-yl]acetate | C16H16ClNO2S | 详情 | 详情 | ||
| 63477 | methyl 2-(2-chlorophenyl)-2-[6,7-dihydrothieno[3,2-c]pyridin-5(4H)-yl]acetate | C16H16ClNO2S | 详情 | 详情 | ||
| (I) | 10202 | Benzoic acid | 65-85-0 | C7H6O2 | 详情 | 详情 |
| (I) | 44623 | C7H6O2 | 详情 | 详情 | ||
| (II) | 10463 | Benzoyl chloride | 98-88-4 | C7H5ClO | 详情 | 详情 |
| (II) | 45137 | C7H5ClO | 详情 | 详情 | ||
| (III) | 21513 | 2-amino-2-methyl-1-propanol；Karl Fischer;2-Amino-2-methyl-propan-1-ol；2-amino-2-methyl-1-propanol | 124-68-5 | C4H11NO | 详情 | 详情 |
| (IV) | 44072 | 4,4-dimethyl-2-phenyl-4,5-dihydro-1,3-oxazole | 19312-06-2 | C11H13NO | 详情 | 详情 |
| (IV) | 45138 | C11H13NO | 详情 | 详情 | ||
| (V) | 44073 | 2-(2-chlorophenyl)-4,4-dimethyl-4,5-dihydro-1,3-oxazole | C11H12ClNO | 详情 | 详情 | |
| (V) | 45139 | C11H12ClNO | 详情 | 详情 | ||
| (VI) | 44074 | 2-(2-chlorophenyl)-3,4,4-trimethyl-4,5-dihydro-1,3-oxazol-3-ium iodide | C12H15ClINO | 详情 | 详情 | |
| (VI) | 45140 | C12H15ClINO | 详情 | 详情 | ||
| (VII) | 44075 | 2-(2-chlorophenyl)-3,4,4-trimethyl-1,3-oxazolidine | C12H16ClNO | 详情 | 详情 | |
| (VII) | 45141 | C12H16ClNO | 详情 | 详情 | ||
| (VIII) | 24114 | 2-chlorobenzaldehyde | 89-98-5 | C7H5ClO | 详情 | 详情 |
| (VIII) | 45142 | C7H5ClO | 详情 | 详情 | ||
| (IX) | 34011 | 4,5,6,7-tetrahydrothieno[3,2-c]pyridine | 54903-50-3 | C7H9NS | 详情 | 详情 |
| (X) | 44076 | 2-(2-chlorophenyl)-2-[6,7-dihydrothieno[3,2-c]pyridin-5(4H)-yl]acetonitrile | C15H13ClN2S | 详情 | 详情 | |
| (X) | 45143 | C15H13ClN2S | 详情 | 详情 | ||
| (XI) | 44077 | 2-(2-chlorophenyl)-2-[6,7-dihydrothieno[3,2-c]pyridin-5(4H)-yl]acetamide | C15H15ClN2OS | 详情 | 详情 | |
| (XI) | 45144 | C15H15ClN2OS | 详情 | 详情 |