Traxoprodil, CO-98113(racemate), CP-101606, -Drug Synthesis Database

【结构式】

【药物名称】Traxoprodil, CO-98113(racemate), CP-101606

【化学名称】(+)-(1S,2S)-1-(4-Hydroxyphenyl)-2-(4-hydroxy-4-phenylpiperidin-1-yl)propan-1-ol

【CA登记号】134234-12-1, 134234-13-2 ([R-(R*,R*)]-isomer), 134138-41-3 (racemic, (R*,R*)-isomer)

【分子式】C₂₀H₂₅NO₃

【分子量】327.42715

【开发单位】Pfizer (Originator), Emory University (Codevelopment), Finch Univ. Health Sci./Chicago Med Sch. (Codevelopment)

【药理作用】Antiparkinsonian Drugs, Cerebrovascular Diseases, Treatment of, Extrapyramidal Disorders, Treatment of, NEUROLOGIC DRUGS, Stroke, Treatment of, NR2B Antagonists

合成路线1 合成路线2

合成路线1

4-Hydroxypropiophenone (I) was protected as the triisopropylsilyl ether (II) and subsequently brominated with elemental bromine in CCl4 . The resultant bromo ketone (III) was subsequently coupled with 4-hydroxy-4-phenylpiperidine (IV) to afford the racemic amino ketone (V). This was stereoselectively reduced with NaBH4 in EtOH yielding the threo-amino alcohol (VI). Then, desilylation of (VI) with tetrabutylammonium fluoride furnished the racemic phenol compound. Resolution into the enantiomers has been reported by formation of the corresponding D-tartaric acid salts

参考文献中间体

【1】 Chenard, B.L.; et al.; (1S,2S)-1-(4-Hydroxyphenyl)-2-(4-hydroxy-4-phenylpiperidino)-1-propanol: A potent new neuroprotectant which blocks N-methyl-D-aspartate responses. J Med Chem 1995, 38, 16, 3138.
【2】 Chenard, B.L. (Pfizer Inc.); 2-Piperidino-1-alkanol derivs. as antiischemic agents. US 5272160 .
【3】 Walinsky, S.W.; Rainville, J.P.; Sinay, T.G. Jr. (Pfizer Products Inc.); Process for the preparation of the mesylate salt trihydrate of 1-(4-hydroxyphenyl)-2-(4-hydroxy-4-phenylpiperidin-1-yl)-1-propanol. EP 1151995 .

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)	58982	4'-Hydroxypropiophenone; 4-Hydroxypropiophenone; Ethyl 4-Hydroxyphenyl ktone; p-Hydroxypropiophenone; Paroxypropione	70-70-2	C₉H₁₀O₂	详情	详情
(II)	62505	1-{4-[(triisopropylsilyl)oxy]phenyl}-1-propanone		C₁₈H₃₀O₂Si	详情	详情
(III)	62506	2-bromo-1-{4-[(triisopropylsilyl)oxy]phenyl}-1-propanone		C₁₈H₂₉BrO₂Si	详情	详情
(IV)	28021	4-phenyl-4-piperidinol; 4-Hydroxy-4-phenylpiperidine; 4-(4-Phenyl)-4-hydroxypiperidine	40807-61-2	C₁₁H₁₅NO	详情	详情
(V)	62507	2-(4-hydroxy-4-phenyl-1-piperidinyl)-1-{4-[(triisopropylsilyl)oxy]phenyl}-1-propanone		C₂₉H₄₃NO₃Si	详情	详情
(VI)	62508	1-((1S,2S)-2-hydroxy-1-methyl-2-{4-[(triisopropylsilyl)oxy]phenyl}ethyl)-4-phenyl-4-piperidinol		C₂₉H₄₅NO₃Si	详情	详情

合成路线2

In a related process, the racemic piperidinyl ketone (VII) was initially resolved employing D-tartaric acid. The target (2S)-piperidinyl propanone (VIII) was then diastereoselectively reduced to the (1S,2S)-alcohol (IX) employing LiBH4 in EtOH. Finally, debenzylation of (IX) by catalytic hydrogenolysis yielded the title compound

参考文献中间体

【1】 Walinsky, S.W.; Rainville, J.P.; Sinay, T.G. Jr. (Pfizer Products Inc.); Process for the preparation of the mesylate salt trihydrate of 1-(4-hydroxyphenyl)-2-(4-hydroxy-4-phenylpiperidin-1-yl)-1-propanol and intermediates useful therefor. EP 1149831 .

中间体序号	中间体编号	品名	分子式	供应商	用于合成
(VIIII)	62512	(2S)-1-[4-(benzyloxy)phenyl]-2-(4-hydroxy-4-phenyl-1-piperidinyl)-1-propanone	C₂₇H₂₉NO₃	详情	详情
(VII)	62510	1-[4-(benzyloxy)phenyl]-2-(4-hydroxy-4-phenyl-1-piperidinyl)-1-propanone	C₂₇H₂₉NO₃	详情	详情
(IX)	62511	1-{(1S,2S)-2-[4-(benzyloxy)phenyl]-2-hydroxy-1-methylethyl}-4-phenyl-4-piperidinol	C₂₇H₃₁NO₃	详情	详情

Extended Information