Udenafil, DA-8159, Zydena, -Drug Synthesis Database

【结构式】

【药物名称】Udenafil, DA-8159, Zydena

【化学名称】3-(1-Methyl-7-oxo-3-propyl-6,7-dihydro-1H-pyrazolo[4,3-d]pyrimidin-5-yl)-N-[2-(1-methylpyrrolidin-2-yl)ethyl]-4-propoxybenzenesulfonamide

【CA登记号】268203-93-6, 319491-68-4

【分子式】C₂₅H₃₆N₆O₄S

【分子量】516.66747

【开发单位】Dong-A (Originator)

【药理作用】RENAL-UROLOGIC DRUGS, Treatment of Erectile Dysfunction, Treatment of Male Sexual Dysfunction, Phosphodiesterase V (PDE5A) Inhibitors

合成路线1 合成路线2

合成路线1

The reaction of 2-propoxybenzoic acid (I) with SOCl2 in refluxing dichloromethane gives the acyl chloride (II), which is condensed with 4-amino-1-methyl-3-propyl-1H-pyrazole-5-carboxamide (III) by means of TEA and DMAP in dichloromethane to yield the carboxamide (IV). The sulfonation of (IV) with chlorosulfonic acid affords the benzenesulfonyl chloride (V), which is treated with 2-(1-methylpyrrolidin-2-yl)ethylamine (VI) in dichloromethane to afford the sulfonamide (VII). Finally, this compound is cyclized by means of tBu-OK in refluxing tert-butanol to provide the target pyrazolo-pyrimidininone.

参考文献中间体

【1】 Kim, S.-H.; Chang, M.-S.; Kim, D.-S.; Yoo, M.-H.; Kim, W.-B.; Bae, C.-J.; Kim, Y.-D.; Kim, E.-H. (Dong-A Pharmaceutical Co., Ltd.); A process for preparing pyrazolopyrimidinone derivs. for the treatment of impotence. WO 0198304 .

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)	53952	2-n-Propoxybenzoic acid	2100-31-4	C₁₀H₁₂O₃	详情	详情
(II)	53953	2-propoxybenzoyl chloride		C₁₀H₁₁ClO₂	详情	详情
(III)	15627	4-amino-1-methyl-3-propyl-1H-pyrazole-5-carboxamide; 4-amino-1-methyl-3-propyl-5-pyrazolecarboxamide	139756-02-8	C₈H₁₄N₄O	详情	详情
(IV)	50253	1-methyl-4-[(2-propoxybenzoyl)amino]-3-propyl-1H-pyrazole-5-carboxamide		C₁₈H₂₄N₄O₃	详情	详情
(V)	50254	3-([[5-(aminocarbonyl)-1-methyl-3-propyl-1H-pyrazol-4-yl]amino]carbonyl)-4-propoxybenzenesulfonyl chloride		C₁₈H₂₃ClN₄O₅S	详情	详情
(VI)	53954	2-(2-Aminoethyl)-1-methylpyrrolidine	n/a	C₇H₁₆N₂	详情	详情
(VII)	53955	1-methyl-4-{[5-({[2-(1-methyl-2-pyrrolidinyl)ethyl]amino}sulfonyl)-2-propoxybenzoyl]amino}-3-propyl-1H-pyrazole-5-carboxamide		C₂₅H₃₈N₆O₅S	详情	详情

合成路线2

The reaction of 5-(chlorosulfonyl)-2-propoxybenzoic acid (I) with 2-(1-methylpyrrolidin-2-yl)ethylamine (II) in acetone gives the sulfonamide (III), which is treated with 2,4,6-trichlorobenzozyl chloride (IV) and TEA to afford the active mixed anhydride (V). The condensation of (V) with 4-amino-1-methyl-3-propyl-1H-pyrazole-5-carboxamide (VI) in dichloromethane provides the corresponding carboxamide (VII). Finally, this compound is cyclized by means of tBu-OK in refluxing tert-butanol to furnish the target pyrrolo-pyrimidinone.

参考文献中间体

【1】 Kim, S.; Kim, H.; Kim, D.S.; Chang, M.S.; Yoo, M.; Lim, J.I.; Ahn, B.O.; Kim, W.; Kim, I.Y.; Lim, T.K.; Kang, K.K.; Son, M.; Doh, M.; Shim, H.; Oh, T.; Kim, D.G. (Dong-A Pharmaceutical Co., Ltd.); Pyrazolopyrimidinone derivs. for the treatment of impotence. EP 1129093; WO 0027848 .

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)	53956	5-(chlorosulfonyl)-2-propoxybenzoic acid		C₁₀H₁₁ClO₅S	详情	详情
(II)	53954	2-(2-Aminoethyl)-1-methylpyrrolidine	n/a	C₇H₁₆N₂	详情	详情
(III)	53957	5-({[2-(1-methyl-2-pyrrolidinyl)ethyl]amino}sulfonyl)-2-propoxybenzoic acid	n/a	C₁₇H₂₆N₂O₅S	详情	详情
(IV)	25718	2,4,6-trichlorobenzoyl chloride	4136-95-2	C₇H₂Cl₄O	详情	详情
(V)	53958	5-({[2-(1-methyl-2-pyrrolidinyl)ethyl]amino}sulfonyl)-2-propoxy-1-benzenecarboxylic 2,4,6-trichloro-1-benzenecarboxylic anhydride	n/a	C₂₄H₂₇Cl₃N₂O₆S	详情	详情
(VI)	15627	4-amino-1-methyl-3-propyl-1H-pyrazole-5-carboxamide; 4-amino-1-methyl-3-propyl-5-pyrazolecarboxamide	139756-02-8	C₈H₁₄N₄O	详情	详情
(VII)	53955	1-methyl-4-{[5-({[2-(1-methyl-2-pyrrolidinyl)ethyl]amino}sulfonyl)-2-propoxybenzoyl]amino}-3-propyl-1H-pyrazole-5-carboxamide		C₂₅H₃₈N₆O₅S	详情	详情

Extended Information

Drug NewChemical Entity Original Patent(3)