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【结 构 式】 
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【药物名称】BTA-243, CL-316243(former code) 【化学名称】(R,R)-5-[2-[2-(3-Chlorophenyl)-2-hydroxyethylamino]propyl]-1,3-benzodioxole-2,2-dicarboxylic acid disodium salt 【CA登记号】138908-40-4, 138908-41-5 ((S, S)-isomer), 151126-84-0 (CL-316243), 139014-45-2 (racemate) 【 分 子 式 】C20H18ClNNa2O7 【 分 子 量 】465.80156 |
【开发单位】Wyeth Pharmaceuticals (Originator) 【药理作用】Antidiabetic Drugs, Antiobesity Drugs, ENDOCRINE DRUGS, METABOLIC DRUGS, Treatment of Nutritional Disorders, Type 2 Diabetes Mellitus, Agents for, beta3-Adrenoceptor Agonists |
合成路线1
The chiral synthesis of CL 316,243 is described: The chiral epoxide (IV) was prepared in a three-step procedure starting from 3-chloroacetophenone. Monochlorination followed by asymmetric reduction gave the chiral chlorohydrin (III), which was treated with base to give the epoxide. The chiral amine was prepared in a six step sequence starting from L-DOPA. Protection of the amine followed by permethylation and ester reduction gave the alcohol (VIII). Conversion to the mesylate followed by catalytic hydrogenation gave enantiomerically pure amine (X). Reaction of the epoxide (IV) with the amine (X) gave the phenethanolamine (XI). Protection as the oxazolidinone (XII) followed by demethylation and subsequent malonation with diethyl dibromomalonate yielded the protected diester (XIV). Basic hydrolysis followed by reverse phase chromatography gave CL 316,243.
| 【1】 Bloom, J.D.; Claus, T.H.; CL 316,243. Drugs Fut 1994, 19, 1, 23. |
| 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) | 15268 | m-chloroacetophenone; 1-(3-chlorophenyl)-1-ethanone | 99-02-5 | C8H7ClO | 详情 | 详情 |
| (II) | 15269 | 2-chloro-1-(3-chlorophenyl)-1-ethanone | C8H6Cl2O | 详情 | 详情 | |
| (III) | 15270 | (1R)-2-chloro-1-(3-chlorophenyl)-1-ethanol | C8H8Cl2O | 详情 | 详情 | |
| (IV) | 15271 | (R)-(+)-3-Chlorostyrene oxide; (2R)-2-(3-Chlorophenyl)oxirane | 62600-71-9 | C8H7ClO | 详情 | 详情 |
| (V) | 15272 | (2S)-2-amino-3-(3,4-dihydroxyphenyl)propionic acid; 3-hydroxy-L-tyrosine; Levodopa | 59-92-7 | C9H11NO4 | 详情 | 详情 |
| (VI) | 15273 | (2S)-2-[(tert-butoxycarbonyl)amino]-3-(3,4-dihydroxyphenyl)propionic acid | C14H19NO6 | 详情 | 详情 | |
| (VII) | 15274 | methyl (2S)-2-[(tert-butoxycarbonyl)amino]-3-(3,4-dimethoxyphenyl)propanoate | C17H25NO6 | 详情 | 详情 | |
| (VIII) | 15275 | tert-butyl N-[(1S)-1-(3,4-dimethoxybenzyl)-2-hydroxyethyl]carbamate | C16H25NO5 | 详情 | 详情 | |
| (IX) | 15276 | tert-butyl N-((1S)-1-(3,4-dimethoxybenzyl)-2-[[methyl(dimethylene)-lambda(6)-sulfanyl]oxy]ethyl)carbamate | C19H31NO5S | 详情 | 详情 | |
| (X) | 15277 | (1R)-2-(3,4-dimethoxyphenyl)-1-methylethylamine; (2R)-1-(3,4-dimethoxyphenyl)-2-propanamine | C11H17NO2 | 详情 | 详情 | |
| (XI) | 15278 | (1R)-1-(3-chlorophenyl)-2-[[(1R)-2-(3,4-dimethoxyphenyl)-1-methylethyl]amino]-1-ethanol | C19H24ClNO3 | 详情 | 详情 | |
| (XII) | 15279 | (5R)-5-(3-chlorophenyl)-3-[(1R)-2-(3,4-dimethoxyphenyl)-1-methylethyl]-1,3-oxazolan-2-one | C20H22ClNO4 | 详情 | 详情 | |
| (XIII) | 15280 | (5R)-5-(3-chlorophenyl)-3-[(1R)-2-(3,4-dihydroxyphenyl)-1-methylethyl]-1,3-oxazolan-2-one | C18H18ClNO4 | 详情 | 详情 | |
| (XIV) | 15281 | diethyl 5-[(2R)-2-[(5R)-5-(3-chlorophenyl)-2-oxo-1,3-oxazolan-3-yl]propyl]-1,3-benzodioxole-2,2-dicarboxylate | C25H26ClNO8 | 详情 | 详情 |