Imidazo[1,2-a]pyridine-6-carbaldehyde -Drug Synthesis Database

【结构式】

【分子编号】12116

【品名】Imidazo[1,2-a]pyridine-6-carbaldehyde

【CA登记号】

【分子式】C₈H₆N₂O

【分子量】146.14852

【元素组成】C 65.75% H 4.14% N 19.17% O 10.95%

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：(IV)

Three related new synthetic routes for E-1020 have been reported: 1) The cyclization of 2-bromoacetaldehyde diethylacetal (I) with 2-aminopyridine-5-carboxylic acid methyl ester (II) by means of HCl in hot water gives imidazo[1,2-a]pyridine-6-carboxylic acid methyl ester (III), which is reduced with dibutylaluminum hydride in dichloromethane to the corresponding aldehyde (IV). The condensation of (IV) with nitroethane (V) by means of butylamine in refluxing ethanol affords 6-(2-nitro-1-propenyl)imidazo[1,2-a]pyridine (VI), which is treated with Fe-FeCl2-HCl in hot ethanol-water to give 1-(imidazo[1,2-a]pyridyl-6-yl)-2-propanone (VII). The condensation of (VII) with dimethylformamide dimethylacetal (VIII) in hot DMF yields 4-(dimethylamino)-3-(imidazo[1,2-a]pyridin-6-yl)-3-buten-2-one (IX), which is finally cyclized with cyanacetamide (X) by means of sodium methoxide in hot DMF. 2) The cyclization of acetal (I) with 2-amino-5-bromopyridine (XI) as before gives 6-bromoimidazo[1,2-a]pyridine (XII), which is condensed with potassium acetylacetonate (XIII) by means of KI and Cu2I2 in hot DMF yielding the adduct (XIV). The cleavage of (XIV) with NaOH and then with HCl gives the propanone (VII), already obtained. 3) The condensation of the bromo derivative (XII) with 3-chloro-2-methylpropene (XV) by means of ethylmagnesium bromide in hot THF gives 6-isobutenylimidazo[1,2-a]pyridine (XVI), which is ozonolyzed with O3 in methanol-water-HCl to yield the propanone (VII), already obtained.

参考文献中间体

合成目标

【1】 Yamanaka, M.; Miyake, K.; Suda, S.; Ohhara, H.; Ogawa, T.; Imidazo[1,2-a]pyridines. I. Synthesis and inotropic activity of new 5-imidazo[1,2-a]pyridinyl-2(1H)-pyridinone derivatives. Chem Pharm Bull 1991, 39, 6, 1556-67.

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)	12113	2-Bromo-1-ethoxyethyl ethyl ether; 2-Bromo-1,1-diethoxyethane; Bromoacetaldehyde diethylacetal	2032-35-1	C₆H₁₃BrO₂	详情	详情
(II)	12114	methyl 6-aminonicotinate		C₇H₈N₂O₂	详情	详情
(III)	12115	methyl imidazo[1,2-a]pyridine-6-carboxylate		C₉H₈N₂O₂	详情	详情
(IV)	12116	Imidazo[1,2-a]pyridine-6-carbaldehyde		C₈H₆N₂O	详情	详情
(V)	12117	Nitroethane; 1-Nitroethane	79-24-3	C₂H₅NO₂	详情	详情
(VI)	12118	6-[(E)-2-Nitro-1-propenyl]imidazo[1,2-a]pyridine		C₁₀H₉N₃O₂	详情	详情
(VII)	12119	1-Imidazo[1,2-a]pyridin-6-ylacetone		C₁₀H₁₀N₂O	详情	详情
(VIII)	11984	N-(Dimethoxymethyl)-N,N-dimethylamine;dimethylformamide dimethylacetal;1,1-dimethoxy-N,N-dimethylmethanamine； Dimethoxy-N,N-dimethylmethanamine; N,N-Dimethylformamide dimethyl acetal	4637-24-5	C₅H₁₃NO₂	详情	详情
(IX)	12121	(Z)-4-(Dimethylamino)-3-imidazo[1,2-a]pyridin-6-yl-3-buten-2-one		C₁₃H₁₅N₃O	详情	详情
(X)	12122	Cyanoacetamide; 2-Cyanoacetamide	107-91-5	C₃H₄N₂O	详情	详情
(XI)	12123	5-Bromo-2-pyridinylamine; 5-Bromo-2-pyridinamine; 2-Amino-5-bromopyridine	1072-97-5	C₅H₅BrN₂	详情	详情
(XII)	12124	6-Bromoimidazo[1,2-a]pyridine	6188-23-4	C₇H₅BrN₂	详情	详情
(XIII)	12125	[2-Methoxy-1-(methoxycarbonyl)-2-oxoethyl]potassium		C₅H₇KO₄	详情	详情
(XIV)	12126	3-Imidazo[1,2-a]pyridin-6-yl-2,4-pentanedione		C₁₂H₁₂N₂O₂	详情	详情
(XV)	12127	3-Chloro-2-methyl-1-propene; Isobutenyl chloride	563-47-3	C₄H₇Cl	详情	详情
(XVI)	12128	6-(2-Methyl-2-propenyl)imidazo[1,2-a]pyridine		C₁₁H₁₂N₂	详情	详情

合成路线2

该中间体在本合成路线中的序号：(VIII)

2) The condensation of imidazo[1,2-a]pyridine-6-carboxaldehyde (VIII) with nitroethane (IX) by means of butylamine in refluxing ethanol gives 6-(2-nitro-1-propenyl)imidazo[1,2-a]pyridine (X), which is treated with FeCl2 and concentrated HCl in refluxing ethanol to afford propanone (IV), already obtained.

参考文献中间体

合成目标

【1】 Miyake, K.; Ohhara, H.; Suda, S.; Toshiaki, O.; Yamanaka, M. (Eisai Co., Ltd.); 5-(6-Imidazo[1,2-a]pyridyl)pyridine derivs.. EP 0199127; ES 8706146; ES 8708230; ES 8708231; ES 8801654; ES 8801655; JP 1986218589; US 4751227 .
【2】 Prous, J.; Castaner, J.; E-1020. Drugs Fut 1988, 13, 6, 514.

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
(IV)	12119	1-Imidazo[1,2-a]pyridin-6-ylacetone		C₁₀H₁₀N₂O	详情	详情
(V)	11984	N-(Dimethoxymethyl)-N,N-dimethylamine;dimethylformamide dimethylacetal;1,1-dimethoxy-N,N-dimethylmethanamine； Dimethoxy-N,N-dimethylmethanamine; N,N-Dimethylformamide dimethyl acetal	4637-24-5	C₅H₁₃NO₂	详情	详情
(VI)	12121	(Z)-4-(Dimethylamino)-3-imidazo[1,2-a]pyridin-6-yl-3-buten-2-one		C₁₃H₁₅N₃O	详情	详情
(VII)	12122	Cyanoacetamide; 2-Cyanoacetamide	107-91-5	C₃H₄N₂O	详情	详情
(VIII)	12116	Imidazo[1,2-a]pyridine-6-carbaldehyde		C₈H₆N₂O	详情	详情
(IX)	12117	Nitroethane; 1-Nitroethane	79-24-3	C₂H₅NO₂	详情	详情
(X)	12118	6-[(E)-2-Nitro-1-propenyl]imidazo[1,2-a]pyridine		C₁₀H₉N₃O₂	详情	详情

Extended Information