KF-72926, -Drug Synthesis Database

【结构式】

【药物名称】KF-72926

【化学名称】2-Cyclopentyl-4-propyl-8(R)-(pyridin-4-ylmethyl)-4,5,7,8-tetrahydro-1H-imidazo[2,1-i]purin-5-one D-tartrate

【CA登记号】349554-69-4, 348165-49-1 (free base)

【分子式】C₂₅H₃₂N₆O₇

【分子量】528.56979

【开发单位】Kyowa Hakko (Originator)

【药理作用】Antidiabetic Drugs, ENDOCRINE DRUGS, Type 2 Diabetes Mellitus, Agents for, Insulin Secretagogues

合成路线1 合成路线2

合成路线1

N-Boc-L-(4-Pyridyl)alanine (I) is deprotected and esterified by means of a methanolic solution of SOCl2 to produce amino ester (II). Subsequent acylation of (II) with benzoyl chloride affords benzamide (III). Ester group reduction in (III) by means of NaBH4 yields alcohol (IV). The amide function of (IV) is then hydrolyzed under acidic conditions to furnish (S)-2-amino-3-(4-pyridyl)-1-propanol (V). Coupling of amino alcohol (V) with the known 6-(methylthio)purine (VI) in hot pyridine leads to adduct (VII). Intramolecular cyclization of the purine alcohol (VII) employing thionyl chloride produces the target tricyclic compound, which is finally isolated as the corresponding D-tartrate salt.

参考文献中间体

【1】 Ueno, K.; et al.; A new class of antidiabetic drugs; insulin secretion potentiator: Synthesis and biological activity of imidazopurine derivatives. 22nd Symp Med Chem (Nov 27 2002, Shizuoka) 2002, Abst 2P-05.
【2】 Nomoto, Y.; Nakanishi, S.; Ohta, Y.; Ogawa, A.; Suzuki, C.; Ueno, K.; Yano, H.; Kusaka, H.; Takasaki, K. (Kyowa Hakko Kogyo Co., Ltd.); Fused purine derivs.. EP 1251130; WO 0147931 .

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)	51044	Boc-D-4-Pyridylalanine; Boc-D-4-Pyridylala	37535-58-3	C₁₃H₁₈N₂O₄	详情	详情
(II)	61411	methyl (2R)-2-amino-3-(4-pyridinyl)propanoate		C₉H₁₂N₂O₂	详情	详情
(III)	61412	methyl (2R)-2-(benzoylamino)-3-(4-pyridinyl)propanoate		C₁₆H₁₆N₂O₃	详情	详情
(IV)	61413	N-[(1R)-2-hydroxy-1-(4-pyridinylmethyl)ethyl]benzamide		C₁₅H₁₆N₂O₂	详情	详情
(V)	61414	(2R)-2-amino-3-(4-pyridinyl)-1-propanol		C₈H₁₂N₂O	详情	详情
(VI)	61415	8-cyclopentyl-6-(methylsulfanyl)-3-propyl-3,7-dihydro-2H-purin-2-one		C₁₄H₂₀N₄OS	详情	详情
(VII)	61416	8-cyclopentyl-6-{[(1R)-2-hydroxy-1-(4-pyridinylmethyl)ethyl]amino}-3-propyl-3,7-dihydro-2H-purin-2-one		C₂₁H₂₈N₆O₂	详情	详情

合成路线2

In a related method, the purine thioether (I) is oxidized to sulfone (II) by means of oxone under phase-transfer conditions. Coupling of sulfone (II) with the pyridyl amino alcohol (III) yields adduct (IV), which is finally cyclized to the target tricyclic compound upon treatment with thionyl chloride.

参考文献中间体

【1】 Nomoto, Y.; Nakanishi, S.; Ohta, Y.; Ogawa, A.; Suzuki, C.; Ueno, K.; Yano, H.; Kusaka, H.; Takasaki, K. (Kyowa Hakko Kogyo Co., Ltd.); Fused purine derivs.. EP 1251130; WO 0147931 .

中间体序号	中间体编号	品名	分子式	供应商	用于合成
(I)	61415	8-cyclopentyl-6-(methylsulfanyl)-3-propyl-3,7-dihydro-2H-purin-2-one	C₁₄H₂₀N₄OS	详情	详情
(II)	61417	8-cyclopentyl-6-(methylsulfonyl)-3-propyl-3,7-dihydro-2H-purin-2-one	C₁₄H₂₀N₄O₃S	详情	详情
(III)	61414	(2R)-2-amino-3-(4-pyridinyl)-1-propanol	C₈H₁₂N₂O	详情	详情
(IV)	61416	8-cyclopentyl-6-{[(1R)-2-hydroxy-1-(4-pyridinylmethyl)ethyl]amino}-3-propyl-3,7-dihydro-2H-purin-2-one	C₂₁H₂₈N₆O₂	详情	详情

Extended Information

Drug NewChemical Entity Original Patent(2)