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【结 构 式】

【分子编号】12124

【品名】6-Bromoimidazo[1,2-a]pyridine

【CA登记号】6188-23-4

【 分 子 式 】C7H5BrN2

【 分 子 量 】197.03418

【元素组成】C 42.67% H 2.56% Br 40.55% N 14.22%

与该中间体有关的原料药合成路线共 2 条

合成路线1

该中间体在本合成路线中的序号:(XII)

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.

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:(I)

1) The condensation of 6-bromoimidazo[1,2-a]-pyridine (I) with 2-(chloromethyl)propene (II) by means of Mg and ethyl bromide in THF gives 6-(2-methyl-2-propenyl)imidazo[1,2-a]pyridine (III), which is ozonolyzed with O3 yielding 1-(imidazo[1,2-a]-pyridin-6-yl)-2-propanone (IV). The condensation of (IV) with dimethylformamide dimethylketal (V) in hot DMF affords 4-(dimethylamino)-3-(imidazo[1,2-a]-pyridin-6-yl)-3-buten-2-one (IV), which is finally cyclized with 2-cyanoacetamide (VII) by means of sodium methoxide in hot DMF.

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
(I) 12124 6-Bromoimidazo[1,2-a]pyridine 6188-23-4 C7H5BrN2 详情 详情
(II) 12127 3-Chloro-2-methyl-1-propene; Isobutenyl chloride 563-47-3 C4H7Cl 详情 详情
(III) 12128 6-(2-Methyl-2-propenyl)imidazo[1,2-a]pyridine C11H12N2 详情 详情
(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
Extended Information