SL-65.0155, SL-650155, -Drug Synthesis Database

【结构式】

【药物名称】SL-65.0155, SL-650155

【化学名称】5-(8-Amino-7-chloro-2,3-dihydro-1,4-benzodioxin-5-yl)-3-[1-(2-phenylethyl)piperidin-4-yl]-1,3,4-oxadiazol-2(3H)-one hydrochloride

【CA登记号】191023-43-5

【分子式】C₂₃H₂₆Cl₂N₄O₄

【分子量】493.39407

【开发单位】Sanofi-synthélabo (Originator)

【药理作用】Alzheimer's Dementia, Treatment of , Cognition Disorders, Treatment of, NEUROLOGIC DRUGS, 5-HT4 Partial Agonists

合成路线1 合成路线2

合成路线1

4-Amino-benzodioxan-1-carboxylic acid (I) is esterified to (II) employing SOCl2 in EtOH. Subsequent chlorination of benzodioxan (II) with N-chlorosuccinimide furnishes (III). The ethyl ester group of (III) is then displaced by hydrazine hydrate to produce the corresponding hydrazide (IV). Cyclization of hydrazide (IV) with phosgene, followed by quenching with benzyl alcohol leads to the oxadiazole derivative (V). This is then coupled with N-Boc-4-piperidinol (VI) under Mitsunobu conditions to yield the piperidinyl oxadiazole (VII). Selective cleavage of the N-Boc protecting group of (VII) by means of trifluoroacetic acid in CH2Cl2 gives rise to piperidine (VIII).

参考文献中间体

【1】 Jegham, S.; Lochead, A.; Galli, F.; Nedelec, A.; Solignac, A.; De Cruz, L. (Sanofi-Synthélabo); 5-Phenyl-3-(piperidin-4-yl)-1,3,4-oxadiazol-2(3H)-one derivs. for use as 5-HT4 or H3 receptor ligands. EP 0863897; FR 2741069; FR 2741070; JP 2000500125; US 5929089; WO 9717345 .

中间体序号	中间体编号	品名	分子式	供应商	用于合成
(I)	63653	8-amino-2,3-dihydro-1,4-benzodioxine-5-carboxylic acid	C₉H₉NO₄	详情	详情
(II)	63654	ethyl 8-amino-2,3-dihydro-1,4-benzodioxine-5-carboxylate	C₁₁H₁₃NO₄	详情	详情
(III)	63655	ethyl 8-amino-7-chloro-2,3-dihydro-1,4-benzodioxine-5-carboxylate	C₁₁H₁₂ClNO₄	详情	详情
(IV)	63656	8-amino-7-chloro-2,3-dihydro-1,4-benzodioxine-5-carbohydrazide	C₉H₁₀ClN₃O₃	详情	详情
(V)	63657	benzyl 6-chloro-8-(5-oxo-4,5-dihydro-1,3,4-oxadiazol-2-yl)-2,3-dihydro-1,4-benzodioxin-5-ylcarbamate	C₁₈H₁₄ClN₃O₆	详情	详情
(VI)	18625	tert-butyl 4-hydroxy-1-piperidinecarboxylate	C₁₀H₁₉NO₃	详情	详情
(VII)	63658	tert-butyl 4-[5-(8-{[(benzyloxy)carbonyl]amino}-7-chloro-2,3-dihydro-1,4-benzodioxin-5-yl)-2-oxo-1,3,4-oxadiazol-3(2H)-yl]-1-piperidinecarboxylate	C₂₈H₃₁ClN₄O₈	详情	详情
(VIII)	63659	benzyl 6-chloro-8-[5-oxo-4-(4-piperidinyl)-4,5-dihydro-1,3,4-oxadiazol-2-yl]-2,3-dihydro-1,4-benzodioxin-5-ylcarbamate	C₂₃H₂₃ClN₄O₆	详情	详情

合成路线2

Piperidine (VIII) is alkylated with phenethyl bromide (IX) to furnish (X). The benzyloxycarbonyl protecting group of (X) is finally removed by treatment with HBr in AcOH to provide the title compound.

参考文献中间体

【1】 Jegham, S.; Lochead, A.; Galli, F.; Nedelec, A.; Solignac, A.; De Cruz, L. (Sanofi-Synthélabo); 5-Phenyl-3-(piperidin-4-yl)-1,3,4-oxadiazol-2(3H)-one derivs. for use as 5-HT4 or H3 receptor ligands. EP 0863897; FR 2741069; FR 2741070; JP 2000500125; US 5929089; WO 9717345 .

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
(VIII)	63659	benzyl 6-chloro-8-[5-oxo-4-(4-piperidinyl)-4,5-dihydro-1,3,4-oxadiazol-2-yl]-2,3-dihydro-1,4-benzodioxin-5-ylcarbamate		C₂₃H₂₃ClN₄O₆	详情	详情
(IX)	20730	1-(2-bromoethyl)benzene；1-Bromo-2-phenylethane;(2-Bromoethyl)benzene;Phenethyl bromide	103-63-9	C₈H₉Br	详情	详情
(X)	63660	benzyl 6-chloro-8-[5-oxo-4-(1-phenethyl-4-piperidinyl)-4,5-dihydro-1,3,4-oxadiazol-2-yl]-2,3-dihydro-1,4-benzodioxin-5-ylcarbamate		C₃₁H₃₁ClN₄O₆	详情	详情

Extended Information

Drug NewChemical Entity Original Patent(1)