3-cyano-4-hydroxybenzohydrazide -Drug Synthesis Database

【结构式】

【分子编号】60848

【品名】3-cyano-4-hydroxybenzohydrazide

【CA登记号】

【分子式】C₈H₇N₃O₂

【分子量】177.1626

【元素组成】C 54.24% H 3.98% N 23.72% O 18.06%

与该中间体有关的原料药合成路线共 3 条

合成路线1 合成路线2 合成路线3

合成路线1

该中间体在本合成路线中的序号：(IV)

Alkylation of the sodium salt of indole-4-carbaldehyde (I) with 2,3,5,6-tetramethylbenzyl chloride (II) affords the N-alkylated indole aldehyde (III). Subsequent condensation of aldehyde (III) with 3-cyano-4-hydroxybenzoic acid hydrazide (IV) in DMSO in the presence of an acidic catalyst yields the target acyl hydrazone.

参考文献中间体

合成目标

【1】 Madsen, P.; Ling, A.; Plewe, M.; et al.; Optimization of alkylidene hydrazide based human glucagon receptor antagonists. Discovery of the highly potent orally available 3-cyano-4-hydroxybenzoic acid [1-(2,3,5,6-tetramethylbenzyl)-1H-indol-4-ylmethylene]hydrazide. J Med Chem 2002, 45, 26, 5755.
【2】 Lau, J.; Madsen, P.; Truesdale, L.K.; Sams, C.; Feng, J.; Kiel, D.; Ling, A.; Kukl, A.; Shi, S.; Plewe, M.B.; May, J. (Agouron Pharmaceuticals, Inc.; Novo Nordisk A/S); Glucagon antagonists/inverse agonists. JP 2002533439; WO 0039088 .

中间体序号	中间体编号	品名	分子式	供应商	用于合成
(I)	62816	1H-indole-4-carbaldehyde	C₉H₇NO	详情	详情
(II)	62817	3-(chloromethyl)-1,2,4,5-tetramethylbenzene	C₁₁H₁₅Cl	详情	详情
(III)	62818	1-(2,3,5,6-tetramethylbenzyl)-1H-indole-4-carbaldehyde	C₂₀H₂₁NO	详情	详情
(IV)	60848	3-cyano-4-hydroxybenzohydrazide	C₈H₇N₃O₂	详情	详情

合成路线2

该中间体在本合成路线中的序号：(VI)

Methyl 4-hydroxybenzoate (I) is iodinated by means of iodine monochloride in hot AcOH, producing (II). Displacement of the aryl iodide (II) with CuCN gives nitrile (III). Then, ester group saponification in (III) leads to 3-cyano-4-hydroxybenzoic acid (IV). Coupling of (IV) with tert-butyl carbazate produces the N-Boc hydrazide (V), which is further deprotected to (VI) by treatment with trifluoroacetic acid

参考文献中间体

合成目标

【1】 Ling, A.; Plewe, M.; Gonzalez, J.; et al.; Human glucagon receptor antagonists based on alkylidene hydrazides. Bioorg Med Chem Lett 2002, 12, 4, 663.
【2】 Gonzales, J.; Sams, C.; Teng, M. (Alanex Corp.; Novo Nordisk A/S); Glucagon antagonists/inverse agonists. EP 0994848; WO 9901423 .

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)	10251	methyl 4-hydroxybenzoate; Methyl p-hydroxybenzoate	99-76-3	C₈H₈O₃	详情	详情
(II)	60844	methyl 4-hydroxy-3-iodobenzoate		C₈H₇IO₃	详情	详情
(III)	60845	methyl 3-cyano-4-hydroxybenzoate		C₉H₇NO₃	详情	详情
(IV)	60846	3-cyano-4-hydroxybenzoic acid		C₈H₅NO₃	详情	详情
(V)	60847	tert-butyl 2-(3-cyano-4-hydroxybenzoyl)-1-hydrazinecarboxylate		C₁₃H₁₅N₃O₄	详情	详情
(VI)	60848	3-cyano-4-hydroxybenzohydrazide		C₈H₇N₃O₂	详情	详情

合成路线3

该中间体在本合成路线中的序号：(VI)

Alkylation of 4-hydroxy-3,5-dimethoxybenzaldehyde (VII) with 4-isopropylbenzyl chloride (VIII) affords the benzyloxy benzaldehyde (IX). Then, condensation of aldehyde (IX) with hydrazide (VI) furnishes the target N-acyl hydrazone

参考文献中间体

合成目标

【1】 Ling, A.; Plewe, M.; Gonzalez, J.; et al.; Human glucagon receptor antagonists based on alkylidene hydrazides. Bioorg Med Chem Lett 2002, 12, 4, 663.
【2】 Gonzales, J.; Sams, C.; Teng, M. (Alanex Corp.; Novo Nordisk A/S); Glucagon antagonists/inverse agonists. EP 0994848; WO 9901423 .

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
(VI)	60848	3-cyano-4-hydroxybenzohydrazide		C₈H₇N₃O₂	详情	详情
(VII)	49243	3,5-Dimethoxy-4-hydroxybenzaldehyde; 4-Hydroxy-3,5-dimethoxybenzaldehyde; Syringaldehyde	134-96-3	C₉H₁₀O₄	详情	详情
(VIII)	33769	1-(chloromethyl)-4-isopropylbenzene	2051-18-5	C₁₀H₁₃Cl	详情	详情
(IX)	60849	4-[(4-isopropylbenzyl)oxy]-3,5-dimethoxybenzaldehyde		C₁₉H₂₂O₄	详情	详情

Extended Information