3-methoxy-2-phenyl-4-quinolinecarboxylic acid -Drug Synthesis Database

【结构式】

【分子编号】23642

【品名】3-methoxy-2-phenyl-4-quinolinecarboxylic acid

【CA登记号】

【分子式】C₁₇H₁₃NO₃

【分子量】279.29516

【元素组成】C 73.11% H 4.69% N 5.02% O 17.19%

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：(III)

Condensation of isatin (I) with 2-methoxyacetophenone (II) in the presence of KOH afforded quinolinecarboxylic acid (III). Subsequent demethylation of the ether function of (III) with refluxing 57% HI gave (IV), which was then condensed with (S)-1-phenylpropyl amine (V) using DCC and HOBt to yield the title amide.

参考文献中间体

合成目标

【1】 Giardina, G.A.M.; et al.; Discovery of a novel class of selective non-peptid. J Med Chem 1999, 42, 6, 1053.

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)	14098	2,3-Indolinedione; 1H-Indole-2,3-dione; Isatin	91-56-5	C₈H₅NO₂	详情	详情
(II)	23641	2-methoxy-1-phenyl-1-ethanone	4079-52-1	C₉H₁₀O₂	详情	详情
(III)	23642	3-methoxy-2-phenyl-4-quinolinecarboxylic acid		C₁₇H₁₃NO₃	详情	详情
(IV)	23643	3-hydroxy-2-phenyl-4-quinolinecarboxylic acid	485-89-2	C₁₆H₁₁NO₃	详情	详情
(V)	23644	(1S)-1-phenylpropylamine; (1S)-1-phenyl-1-propanamine	3789-59-1	C₉H₁₃N	详情	详情

合成路线2

该中间体在本合成路线中的序号：(III)

The quinolinecarboxylic acid (III) was obtained by the Pfitzinger reaction of isatin (I) with 2-methoxyacetophenone (II) in ethanolic KOH at 80 C. Subsequent methyl ether cleavage in (III) using concentrated HI provided 3-hydroxy-2-phenylquinoline-4-carboxylic acid (IV). Coupling of acid (IV) with (S)-1-phenylpropylamine (V) by means of DCC and HOBt gave amide (VI). Ester (VIII) was then obtained by alkylation of the 3-hydroxy quinoline (VI) with ethyl bromoacetate (VII) in the presence of K2CO3 and KI. Finally, hydrolysis of the ethyl ester (VIII) with refluxing HCl afforded the corresponding carboxylic acid.

参考文献中间体

合成目标

【1】 Giardina, G.A.M.; et al.; Discovery of a novel class of selective non-peptid. J Med Chem 1999, 42, 6, 1053.
【2】 Giardina, G.A.M.; Grugni, M.; Raveglia, L.F.; Farino, C. (GlaxoSmithKline plc); Quinoline derivs.. EP 0876347; JP 2000501104; US 6277862; WO 9721680 .

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)	14098	2,3-Indolinedione; 1H-Indole-2,3-dione; Isatin	91-56-5	C₈H₅NO₂	详情	详情
(II)	23641	2-methoxy-1-phenyl-1-ethanone	4079-52-1	C₉H₁₀O₂	详情	详情
(III)	23642	3-methoxy-2-phenyl-4-quinolinecarboxylic acid		C₁₇H₁₃NO₃	详情	详情
(IV)	23643	3-hydroxy-2-phenyl-4-quinolinecarboxylic acid	485-89-2	C₁₆H₁₁NO₃	详情	详情
(V)	23644	(1S)-1-phenylpropylamine; (1S)-1-phenyl-1-propanamine	3789-59-1	C₉H₁₃N	详情	详情
(VI)	58526	3-hydroxy-2-phenyl-N-[(1S)-1-phenylpropyl]-4-quinolinecarboxamide		C₂₅H₂₂N₂O₂	详情	详情
(VII)	16640	Ethyl 2-bromoacetate; Ethyl bromoacetate	105-36-2	C₄H₇BrO₂	详情	详情
(VIII)	58527	ethyl 2-{[2-phenyl-4-({[(1S)-1-phenylpropyl]amino}carbonyl)-3-quinolinyl]oxy}acetate		C₂₉H₂₈N₂O₄	详情	详情

Extended Information