QF-2004B, -Drug Synthesis Database

【结构式】

【药物名称】QF-2004B

【化学名称】2-[4-(6-Fluorobenzisoxazol-3-yl)piperidin-1-ylmethyl]-2,3,4,9-tetrahydro-1H-carbazol-4-one

【CA登记号】

【分子式】C₂₅H₂₄FN₃O₂

【分子量】417.48733

【开发单位】Universidad de Santiago de Compostela (Originator)

【药理作用】Antipsychotic Drugs, PSYCHOPHARMACOLOGIC DRUGS, 5-HT2A Antagonists, Dopamine D2 Antagonists

合成路线1 合成路线2

合成路线1

The reduction of 3,5-dimethoxybenzoic acid (I) first with Li in liquid NH3 and methanol, and then with LiAlH4 in THF gives 3,5-dimethoxy-1,4-dihydrobenzyl alcohol (II), which is cyclized with phenylhydrazine (III) in refluxing 4% sulfuric acid yielding 2-(hydroxymethyl)-1,2,3,4-tetrahydrocarbazol-4-one (IV). The reaction of (IV) with tosyl chloride in pyridine affords the corresponding tosylate (V), which is finally condensed with 4-(6-fluoro-1,2-benzisoxazol-3-yl)piperidine (VI) in N-methyl-2-pyrrolidone.

参考文献中间体

【1】 Masaguer, C.F.; Formoso, E.; Raviña, E.; Tristán, H.; Loza, M.I.; Rivas, E.; Fontenla, J.A.; Butyrophenone analogues in the carbazole series: Synthesis and determination of affinities at D2 and 5-HT2A receptors. Bioorg Med Chem Lett 1998, 8, 24, 3571.

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)	22761	3,5-dimethoxybenzoic acid	1132-21-4	C₉H₁₀O₄	详情	详情
(II)	25566	(3,5-dimethoxy-2,5-cyclohexadien-1-yl)methanol		C₉H₁₄O₃	详情	详情
(III)	11818	Phenyl hydrazine; 1-Phenylhydrazine	100-63-0	C₆H₈N₂	详情	详情
(IV)	25567	2-(hydroxymethyl)-1,2,3,9-tetrahydro-4H-carbazol-4-one		C₁₃H₁₃NO₂	详情	详情
(V)	25568	(4-oxo-2,3,4,9-tetrahydro-1H-carbazol-2-yl)methyl 4-methylbenzenesulfonate		C₂₀H₁₉NO₄S	详情	详情
(VI)	17910	6-fluoro-3-(4-piperidinyl)-1,2-benzisoxazole		C₁₂H₁₃FN₂O	详情	详情

合成路线2

The condensation of 3,5-dimethoxybenzoic acid (I) with 4-(6-fluoro-1,2-benzisoxazol-3-yl)piperidine (II) by means of DCC and HOBT in DMF gives the piperidide (III), which is reduced with LiAlH4 in THF to yield 1-(3,5-dimethoxybenzyl)-4-(6-fluoro-1,2-benzisoxazol-3-yl)piperidine (IV). The reduction of (IV) with Li in liquid ammonia affords the 1,4-dihydro derivative (V), which is finally cyclized with phenylhydrazine (VI) in refluxing aqueous sulfuric acid to provide the target tetrahydrocarbazolone.

参考文献中间体

【1】 Masaguer, C.F.; Loza, M.I.; Fontenla, J.A.; Brea, J.; Raviña, E.; Tristan, H.; Butyrophenone analogues in the carbazole series as potential atypical antipsychotics: Synthesis and determination of affinities at D2, 5-HT2A, 5-HT2B and 5-HT2C receptors. Eur J Med Chem 2000, 35, 1, 83.

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)	22761	3,5-dimethoxybenzoic acid	1132-21-4	C₉H₁₀O₄	详情	详情
(II)	17910	6-fluoro-3-(4-piperidinyl)-1,2-benzisoxazole		C₁₂H₁₃FN₂O	详情	详情
(III)	51420	(3,5-dimethoxyphenyl)[4-(6-fluoro-1,2-benzisoxazol-3-yl)-1-piperidinyl]methanone		C₂₁H₂₁FN₂O₄	详情	详情
(IV)	51418	3-[1-(3,5-dimethoxybenzyl)-4-piperidinyl]-6-fluoro-1,2-benzisoxazole; 3-[[4-(6-fluoro-1,2-benzisoxazol-3-yl)-1-piperidinyl]methyl]-5-methoxyphenyl methyl ether		C₂₁H₂₃FN₂O₃	详情	详情
(V)	51419	3-[[4-(6-fluoro-1,2-benzisoxazol-3-yl)-1-piperidinyl]methyl]-5-methoxy-1,4-cyclohexadien-1-yl methyl ether; 3-[1-[(3,5-dimethoxy-2,5-cyclohexadien-1-yl)methyl]-4-piperidinyl]-6-fluoro-1,2-benzisoxazole		C₂₁H₂₅FN₂O₃	详情	详情
(VI)	11818	Phenyl hydrazine; 1-Phenylhydrazine	100-63-0	C₆H₈N₂	详情	详情

Extended Information

Drug NewChemical Entity Original Patent(1)