Boc-nipecotic acid -Drug Synthesis Database

【结构式】

【分子编号】57078

【品名】Boc-nipecotic acid

【CA登记号】

【分子式】C₁₁H₁₉NO₄

【分子量】229.2762

【元素组成】C 57.63% H 8.35% N 6.11% O 27.91%

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：(II)

Acylation of 6,7-dimethoxy-1,2,3,4-tetrahydroisoquinoline (I) with N-Boc-nipecotic acid (II) by means of EDC/HOBt gives amide (III). Subsequent acidic cleavage of the Boc protecting group yields amine (IV). 3,4-Methylenedioxyaniline (V) is acylated by acryloyl chloride in the presence of Et3N to produce the acrylanilide (VI). Then, Michael addition of piperidine (IV) to the acrylanilide (VI) in boiling toluene provides the title compound.

参考文献中间体

合成目标

【1】 Kakefuda, A.; Okazaki, T.; Watanabe, T.; et al.; Structure-activity relationships of novel 1,2,3,4-tetrahydroisoquinolin derivatives as bradycardic agents. Drugs Fut 2002, 27, Suppl. A.
【2】 Okazaki, T.; Watanabe, T.; Wada, K.; Kakefuda, A.; Masuda, N. (Yamanouchi Pharmaceutical Co., Ltd.); Novel isoquinoline derivs. or salts thereof. EP 1186601; WO 0075133 .

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)	25859	6,7-dimethoxy-1,2,3,4-tetrahydroisoquinoline; 6-methoxy-1,2,3,4-tetrahydro-7-isoquinolinyl methyl ether		C₁₁H₁₅NO₂	详情	详情
(II)	57078	Boc-nipecotic acid		C₁₁H₁₉NO₄	详情	详情
(III)	58821	tert-butyl 3-{[6,7-dimethoxy-3,4-dihydro-2(1H)-isoquinolinyl]carbonyl}-1-piperidinecarboxylate		C₂₂H₃₂N₂O₅	详情	详情
(IV)	58822	[6,7-dimethoxy-3,4-dihydro-2(1H)-isoquinolinyl](3-piperidinyl)methanone		C₁₇H₂₄N₂O₃	详情	详情
(V)	10984	1,3-Benzodioxol-5-amine; 1,3-Benzodioxol-5-ylamine.; 3,4-(Methylenedioxy)aniline	14268-66-7	C₇H₇NO₂	详情	详情
(VI)	58823	N-(1,3-benzodioxol-5-yl)acrylamide		C₁₀H₉NO₃	详情	详情

合成路线2

该中间体在本合成路线中的序号：(I)

Condensation between N-Boc-nipecotic acid (I) and 2,3-di-O-benzyl ascorbic acid (II) using DCC in the presence of DMAP leads to ester (III). Subsequent removal of the N-Boc group of (III) with trifluoroacetic acid gives the N-deprotected nipecotate (IV). This is finally debenzylated by catalytic hydrogenolysis over Pd/C to furnish the title compound.

参考文献中间体

合成目标

【1】 Manfredini, S.; Pavan, B.; Vertuani, S.; et al.; Design, synthesis and activity of ascorbic acid prodrugs of nipecotic, kynurenic and diclophenamic acids, liable to increase neurotropic activity. J Med Chem 2002, 45, 3, 559.
【2】 Manfredini, S. (Università di Ferrara); Prodrugs derivs. of the ascorbic acid suitable to the passage of the hematoencephalic barrier. WO 0270499 .

中间体序号	中间体编号	品名	分子式	供应商	用于合成
(I)	57078	Boc-nipecotic acid	C₁₁H₁₉NO₄	详情	详情
(II)	57075	(5R)-3,4-bis(benzyloxy)-5-[(1S)-1,2-dihydroxyethyl]-2(5H)-furanone	C₂₀H₂₀O₆	详情	详情
(III)	57076	3-{(2S)-2-[(2R)-3,4-bis(benzyloxy)-5-oxo-2,5-dihydro-2-furanyl]-2-hydroxyethyl} 1-(tert-butyl) 1,3-piperidinedicarboxylate	C₃₁H₃₇NO₉	详情	详情
(IV)	57077	(2S)-2-[(2R)-3,4-bis(benzyloxy)-5-oxo-2,5-dihydro-2-furanyl]-2-hydroxyethyl 3-piperidinecarboxylate	C₂₆H₂₉NO₇	详情	详情

Extended Information