-Drug Synthesis Database

【结构式】

【药物名称】

【化学名称】7(R)-Isopropyl-5-methyl-2-(4-methylpentyl)-4,5,7,8-tetrahydro-3H-imidazo[2,1-b]purin-4-one

【CA登记号】

【分子式】C₁₇H₂₇N₅O

【分子量】317.43764

【开发单位】Schering-Plough (Originator)

【药理作用】CARDIOVASCULAR DRUGS, Heart Failure Therapy, Hypertension, Treatment of, Phosphodiesterase I Inhibitors, Phosphodiesterase V (PDE5A) Inhibitors

合成路线1

The acylation of 6-amino-5-(benzylamino)-2-methylpyrimidine-2,4(1H,3H)-dione (I) with 5-methylhexanoic acid (II) by means of EDCI and DMAP gives the amide (III), which is cyclized by means of hot POCl3 affording the chloropurin-6-one (IV). The condensation of (IV) with the chiral aminoalcohol (V) by means of DIEA and NMP yields intermediate (VI), which is cyclized by means of SOCl2 in dichloromethane providing the imidazo-purine (VII). Finally, this compound is debenzylated with ammonium formate and Pd(OH)2.

参考文献中间体

【1】 Ho, G.D.; Silverman, L.; Bercovivi, A.; Puchalski, C.; Tulshian, D.; Xia, Y.; Czarniecki, M.; Green, M.; Cleven, R.; Zhang, H.; Fawzi, A.; Synthesis and evaluation of potent and selective c-GMP phosphodiesterase inhibitors. Bioorg Med Chem Lett 1999, 9, 1, 7.

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)	27648	6-amino-5-(benzylamino)-3-methyl-2,4(1H,3H)-pyrimidinedione		C₁₂H₁₄N₄O₂	详情	详情
(II)	27649	5-methylhexanoic acid	628-46-6	C₇H₁₄O₂	详情	详情
(III)	27650	N-(6-amino-3-methyl-2,4-dioxo-1,2,3,4-tetrahydro-5-pyrimidinyl)-N-benzyl-5-methylhexanamide		C₁₉H₂₆N₄O₃	详情	详情
(IV)	27651	7-benzyl-2-chloro-1-methyl-8-(4-methylpentyl)-1,7-dihydro-6H-purin-6-one		C₁₉H₂₃ClN₄O	详情	详情
(V)	27652	(2R)-2-amino-3-methyl-1-butanol; (R-(-))-Valinol; D-Valinol	4276-09-9	C₅H₁₃NO	详情	详情
(VI)	27653	7-benzyl-2-[[(1R)-1-(hydroxymethyl)-2-methylpropyl]amino]-1-methyl-8-(4-methylpentyl)-1,7-dihydro-6H-purin-6-one		C₂₄H₃₅N₅O₂	详情	详情
(VII)	27654	(7R)-3-benzyl-7-isopropyl-5-methyl-2-(4-methylpentyl)-7,8-dihydro-3H-imidazo[2,1-b]purin-4(5H)-one		C₂₄H₃₃N₅O	详情	详情

Extended Information

Drug NewChemical Entity Original Patent(1)