Boc-D-4-Pyridylalanine; Boc-D-4-Pyridylala -Drug Synthesis Database

【结构式】

【分子编号】51044

【品名】Boc-D-4-Pyridylalanine; Boc-D-4-Pyridylala

【CA登记号】37535-58-3

【分子式】C₁₃H₁₈N₂O₄

【分子量】266.297

【元素组成】C 58.63% H 6.81% N 10.52% O 24.03%

与该中间体有关的原料药合成路线共 2 条

合成路线1 合成路线2

合成路线1

该中间体在本合成路线中的序号：(I)

Coupling of N-Boc-D-pyridylalanine (I) to glycine methyl ester (II) produced the protected dipeptide (III). Subsequent catalytic hydrogenation of the pyridine ring of (III) over PtO2 gave piperidine (IV), which was then treated with the guanylating reagent (V) to afford the guanidine derivative (VI). Acid cleavage of the Boc protecting group of (VI) provided amine (VII). This was condensed with benzylsulfonyl chloride to give sulfonamide (VIII). After basic hydrolysis of the methyl ester of (VIII), the resultant carboxylic acid (IX) was coupled to nitroargininal ethyl aminal (X), yielding amide (XI).

参考文献中间体

合成目标

【1】 Levy, O.E.; Uong, T.H.; Tamura, S.Y.; et al.; Guanylpiperidine peptidomimetics: Potent and selective bis-cation inhibitors of factor Xa. Bioorg Med Chem Lett 2000, 10, 8, 745.

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)	17568	methyl 2-aminoacetate		C₃H₇NO₂	详情	详情
(III)	51045	methyl 2-[[(2R)-2-[(tert-butoxycarbonyl)amino]-3-(4-pyridinyl)propanoyl]amino]acetate		C₁₆H₂₃N₃O₅	详情	详情
(IV)	51046	methyl 2-[[(2R)-2-[(tert-butoxycarbonyl)amino]-3-(4-piperidinyl)propanoyl]amino]acetate		C₁₆H₂₉N₃O₅	详情	详情
(V)	32861	benzyl (E)-[[(benzyloxy)carbonyl]amino](methylsulfanyl)methylidenecarbamate		C₁₈H₁₈N₂O₄S	详情	详情
(VI)	51047	methyl 2-([(2R)-3-[1-([[(benzyloxy)carbonyl]amino][[(benzyloxy)carbonyl]imino]methyl)-4-piperidinyl]-2-[(tert-butoxycarbonyl)amino]propanoyl]amino)acetate		C₃₃H₄₃N₅O₉	详情	详情
(VII)	51048	methyl 2-([(2R)-2-amino-3-[1-([[(benzyloxy)carbonyl]amino][[(benzyloxy)carbonyl]imino]methyl)-4-piperidinyl]propanoyl]amino)acetate		C₂₈H₃₅N₅O₇	详情	详情
(VIII)	51049	methyl 2-([(2R)-3-[1-([[(benzyloxy)carbonyl]amino][[(benzyloxy)carbonyl]imino]methyl)-4-piperidinyl]-2-[(benzylsulfonyl)amino]propanoyl]amino)acetate		C₃₅H₄₁N₅O₉S	详情	详情
(IX)	51050	2-([(2R)-3-[1-([[(benzyloxy)carbonyl]amino][[(benzyloxy)carbonyl]imino]methyl)-4-piperidinyl]-2-[(benzylsulfonyl)amino]propanoyl]amino)acetic acid		C₃₄H₃₉N₅O₉S	详情	详情
(X)	29388	3(S)-Amino-2-ethoxy-N2-nitropiperidine-1-carboxamidine		C₈H₁₇N₅O₃	详情	详情
(XI)	51051			C₄₂H₅₄N₁₀O₁₁S	详情	详情

合成路线2

该中间体在本合成路线中的序号：(I)

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

合成目标

【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

Extended Information