CI-1030, PD-172760, -Drug Synthesis Database

【结构式】

【药物名称】CI-1030, PD-172760

【化学名称】7-[4-(4-Chlorophenyl)piperazin-1-ylmethyl]-3,4-dihydro-2H-1,4-benzoxazin-3-one

【CA登记号】200195-01-3

【分子式】C₁₉H₂₀ClN₃O₂

【分子量】357.84315

【开发单位】Pfizer (Originator)

【药理作用】Antipsychotic Drugs, PSYCHOPHARMACOLOGIC DRUGS, Dopamine D4 Antagonists

合成路线1 合成路线2

合成路线1

3-Hydroxy-4-nitrobenzaldehyde (I) was treated with 1,3-propanediol (II) in the presence of p-toluenesulfonic acid to afford the corresponding acetal (III). Catalytic hydrogenation of the nitro group of (III) over Raney-Ni gave aniline (IV), which was then acylated with chloroacetyl chloride (V) in the presence of NaHCO3 to the chloroacetamide (VI). The acetal function of (VI) was hydrolyzed with HCl in aqueous MeOH, and subsequent cyclization of the chloroacetamide (VII) using K2CO3 in acetonitrile produced the formylbenzoxazinone (VIII). The target compound was then prepared by reductive condensation of aldehyde (VIII) with N-(4-chlorophenyl)piperazine (IX) in the presence of sodium triacetoxyborohydride and AcOH.

参考文献中间体

【1】 Brink, W.A.; Wustrow, D.J.; Belliotti, T.R.; et al.; A series of 6- and 7-piperazinyl- and -piperidinylmethylbenzoxazinones with dopamine D4 antagonist activity: Discovery of a potential atypical antipsychotic agent. J Med Chem 1999, 42, 25, 5181.
【2】 Belliotti, T.; Wise, L.D.; Wustrow, D.J. (Pfizer Inc.); Benzoxazinone dopamine D4 receptor antagonists. EP 0906294; WO 9745419 .

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)	21032	3-hydroxy-4-nitrobenzaldehyde		C₇H₅NO₄	详情	详情
(III)	21034	5-(1,3-dioxan-2-yl)-2-nitrophenol		C₁₀H₁₁NO₅	详情	详情
(IV)	21035	(rac)-2-amino-5-(1,3-dioxan-2-yl)phenol		C₁₀H₁₃NO₃	详情	详情
(V)	11296	2-Chloroacetyl chloride; Chloroacetic chloride	79-04-9	C₂H₂Cl₂O	详情	详情
(VI)	21037	2-chloro-N-[4-(1,3-dioxan-2-yl)-2-hydroxyphenyl]acetamide		C₁₂H₁₄ClNO₄	详情	详情
(VII)	21038	2-chloro-N-(4-formyl-2-hydroxyphenyl)acetamide		C₉H₈ClNO₃	详情	详情
(VIII)	21039	3-oxo-3,4-dihydro-2H-1,4-benzoxazine-7-carbaldehyde		C₉H₇NO₃	详情	详情

合成路线2

The reduction of 3-oxo-3,4-dihydro-2H-1,4-benzoxazine-7-carbaldehyde (I) with NaBH4 in methanol gives the corresponding carbinol (II), which is acylated with TsCl in pyridine yielding the tosylate (III). Finally, this compound is condensed with 1-(4-chlorophenyl)piperazine (IV) by means of K2CO3 in refluxing acetonitrile.

参考文献中间体

【1】 Brink, W.A.; Wustrow, D.J.; Belliotti, T.R.; et al.; A series of 6- and 7-piperazinyl- and -piperidinylmethylbenzoxazinones with dopamine D4 antagonist activity: Discovery of a potential atypical antipsychotic agent. J Med Chem 1999, 42, 25, 5181.

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)	21039	3-oxo-3,4-dihydro-2H-1,4-benzoxazine-7-carbaldehyde		C₉H₇NO₃	详情	详情
(II)	36522	7-(hydroxymethyl)-2H-1,4-benzoxazin-3(4H)-one		C₉H₉NO₃	详情	详情
(III)	36523	(3-oxo-3,4-dihydro-2H-1,4-benzoxazin-7-yl)methyl 4-methylbenzenesulfonate		C₁₆H₁₅NO₅S	详情	详情
(IV)	33593	1-(4-chlorophenyl)piperazine	38869-46-4	C₁₀H₁₃ClN₂	详情	详情

Extended Information

Drug NewChemical Entity Original Patent(1)