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【结 构 式】

【分子编号】12123

【品名】5-Bromo-2-pyridinylamine; 5-Bromo-2-pyridinamine; 2-Amino-5-bromopyridine

【CA登记号】1072-97-5

【 分 子 式 】C5H5BrN2

【 分 子 量 】173.01218

【元素组成】C 34.71% H 2.91% Br 46.18% N 16.19%
与该中间体有关的原料药合成路线共 16 条
合成路线1合成路线2合成路线3合成路线4合成路线5合成路线6合成路线7合成路线8合成路线9合成路线10合成路线11合成路线12合成路线13合成路线14合成路线15合成路线16

合成路线1

该中间体在本合成路线中的序号：(XI)

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：(I)

The acetylation of 5-bromopyridine-2-amine (I) with acetic anhydride in AcOH gives the expected amide (II), which is alkylated with ethylene by means of palladium acetate, tri p-tolylphosphine and triethylamine in hot acetonitrile to yield N-(5-vinylpyridin-2-yl)acetamide (III). The regioselective dihydroxylation of the vinyl group of (III) with AD-Mix-B in tert-butanol affords N-[5-(1(R),2-dihydroxyethyl)pyridin-2-yl]acetamide (IV), which is monotosylated with Ts-Cl in cool pyridine to give the tosylate (V). The reaction of (V) with potassium tert.-butoxide in THF yields the epoxide (VI), which is condensed with 2-[4-(2-aminoethoxy)phenyl]-N-methylacetamide (VII) in hot toluene/DMSO to provide the expected addition product (VIII). Finally, this compound is treated with 6N HCl on a steam bath. The intermediate 2-[4-(2-aminoethoxy)phenyl]-N-methylacetamide (VII) has been obtained as follows: The reaction of benzyl chloroformate (IX) with ethanolamine (X) by means of NaHCO3 in water gives the carbamate (XI), which is condensed with 2-(4-hydroxyphenyl)-N-methylacetamide (XII) (obtained by reaction of the corresponding methyl ester (XIII) with methylamine), by means of PPh3 and diisopropyl azodicarboxylate (DIAD) in THF yielding the intermediate (XIV). Finally, this compound is submitted to elimination of the carbamate protecting group by hydrogenation with H2 over Pd/C in methanol to provide the target intermediate (VII).

参考文献 中间体
合成目标
【1】 Dow, R.L. (Pfizer Inc.); beta-Adrenergic agonists to reduce a wasting condition. EP 0887079 .
【2】 Devries, K.M.; Dow, R.L.; Wright, S.W. (Pfizer Inc.); Process for substd. pyridines. EP 0938476; WO 9821184 .
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) 12123 5-Bromo-2-pyridinylamine; 5-Bromo-2-pyridinamine; 2-Amino-5-bromopyridine 1072-97-5 C5H5BrN2 详情 详情
(II) 32490 N-(5-bromo-2-pyridinyl)acetamide C7H7BrN2O 详情 详情
(III) 32491 N-(5-vinyl-2-pyridinyl)acetamide C9H10N2O 详情 详情
(IV) 32492 N-[5-[(1R)-1,2-dihydroxyethyl]-2-pyridinyl]acetamide C9H12N2O3 详情 详情
(V) 32493 (2R)-2-[6-(acetamido)-3-pyridinyl]-2-hydroxyethyl 4-methylbenzenesulfonate C16H18N2O5S 详情 详情
(VI) 32494 N-[5-[(2R)oxiranyl]-2-pyridinyl]acetamide C9H10N2O2 详情 详情
(VII) 32495 2-[4-(2-aminoethoxy)phenyl]-N-methylacetamide C11H16N2O2 详情 详情
(VIII) 32496 2-[4-[2-([(2R)-2-[6-(acetamido)-3-pyridinyl]-2-hydroxyethyl]amino)ethoxy]phenyl]-N-methylacetamide C20H26N4O4 详情 详情
(IX) 10101 Benzyloxycarbonyl chloride; Benzyl chloroformate; 1-[[(Chlorocarbonyl)oxy]methyl]benzene 501-53-1 C8H7ClO2 详情 详情
(X) 10259 Ethanol amine;Ethanolamine;2-Aminoethanol; 2-Amino-1-ethanol；2-Aminoethyl alcohol 141-43-5 C2H7NO 详情 详情
(XI) 32497 benzyl 2-hydroxyethylcarbamate 77987-49-6 C10H13NO3 详情 详情
(XII) 32498 2-(4-hydroxyphenyl)-N-methylacetamide C9H11NO2 详情 详情
(XIII) 15822 Methyl 4-hydroxyphenylacetate; methyl 2-(4-hydroxyphenyl)acetate 14199-15-6 C9H10O3 详情 详情
(XIV) 32499 benzyl 2-[4-[2-(methylamino)-2-oxoethyl]phenoxy]ethylcarbamate C19H22N2O4 详情 详情

合成路线3

该中间体在本合成路线中的序号：(I)

Condensation of 2-amino-5-bromopyridine (I) with 1,1-thiocarbonyl diimidazole (II) furnished the thiocarbonyl derivative (III). Further reaction of (III) with 1-(2-aminoethyl)piperidine (IV) gave the target thiourea.

参考文献 中间体
合成目标
【1】 Mao, C.; Vig, R.; Venkatachalam, T.K.; Sudbeck, E.A.; Uckun, F.M.; Structure-based design of N-[2-(1-piperidinylethyl)]-N'-[2-(5-bromopyridyl)]-thiourea and N-[2-(1-piperazinylethyl)]-N'-[2-(5-bromopyridyl)]-thiourea as potent non-nucleoside inhibitors of HIV-1 reverse transcriptase. Bioorg Med Chem Lett 1998, 8, 16, 2213.
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) 12123 5-Bromo-2-pyridinylamine; 5-Bromo-2-pyridinamine; 2-Amino-5-bromopyridine 1072-97-5 C5H5BrN2 详情 详情
(II) 11990 Di(1H-imidazol-1-yl)methanethione; 1,1'-Thiocarbonyldiimidazole 6160-65-2 C7H6N4S 详情 详情
(III) 24645 N-(5-bromo-2-pyridinyl)-1H-imidazole-1-carbothioamide C9H7BrN4S 详情 详情
(IV) 24646 2-(1-piperidinyl)-1-ethanamine 27578-60-5 C7H16N2 详情 详情

合成路线4

该中间体在本合成路线中的序号：(I)

Condensation of 2-amino-5-bromopyridine (I) with 1,1-thiocarbonyl diimidazole (II) furnished the thiocarbonyl derivative (III). Further reaction of (III) with 1-(2-aminoethyl)piperazine (IV) gave the target thiourea.

参考文献 中间体
合成目标
【1】 Mao, C.; Vig, R.; Venkatachalam, T.K.; Sudbeck, E.A.; Uckun, F.M.; Structure-based design of N-[2-(1-piperidinylethyl)]-N'-[2-(5-bromopyridyl)]-thiourea and N-[2-(1-piperazinylethyl)]-N'-[2-(5-bromopyridyl)]-thiourea as potent non-nucleoside inhibitors of HIV-1 reverse transcriptase. Bioorg Med Chem Lett 1998, 8, 16, 2213.
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) 12123 5-Bromo-2-pyridinylamine; 5-Bromo-2-pyridinamine; 2-Amino-5-bromopyridine 1072-97-5 C5H5BrN2 详情 详情
(II) 11990 Di(1H-imidazol-1-yl)methanethione; 1,1'-Thiocarbonyldiimidazole 6160-65-2 C7H6N4S 详情 详情
(III) 24645 N-(5-bromo-2-pyridinyl)-1H-imidazole-1-carbothioamide C9H7BrN4S 详情 详情
(IV) 24647 2-(1-piperazinyl)-1-ethanamine 140-31-8 C6H15N3 详情 详情

合成路线5

该中间体在本合成路线中的序号：(I)

2-Amino-5-bromopyridine (I) was condensed with 1,1-thiocarbonyldiimidazole (II) in acetonitrile to furnish the precursor thiocarbonyl derivative (III). Further reaction of (III) with 2-chlorophenethylamine (IV) in DMF at 100 C gave the target thiourea.

参考文献 中间体
合成目标
【1】 Vig, R.; Mao, C.; Venkatachalam, T.K.; Tuel-Ahlgren, L.; Sudbeck, E.A.; Uckun, F.M.; Rational design and synthesis of phenethyl-5-bromopyridyl thiourea derivatives as potent non-nucleoside inhibitors of HIV reverse transcriptase. Bioorg Med Chem 1998, 6, 10, 1789.
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) 12123 5-Bromo-2-pyridinylamine; 5-Bromo-2-pyridinamine; 2-Amino-5-bromopyridine 1072-97-5 C5H5BrN2 详情 详情
(II) 11990 Di(1H-imidazol-1-yl)methanethione; 1,1'-Thiocarbonyldiimidazole 6160-65-2 C7H6N4S 详情 详情
(III) 26465 methyl (2S,3R)-3-cyclopropyl-2,3-dihydroxypropanoate C7H12O4 详情 详情
(IV) 31334 2-chlorophenethylamine; 2-(2-chlorophenyl)-1-ethanamine 13078-80-3 C8H10ClN 详情 详情

合成路线6

该中间体在本合成路线中的序号：(I)

2-Amino-5-bromopyridine (I) was condensed with 1,1-thiocarbonyldiimidazole (II) in acetonitrile to furnish the precursor thiocarbonyl derivative (III). Further reaction of (III) with 3-chlorophenethylamine (IV) in DMF at 100 C gave the target thiourea.

参考文献 中间体
合成目标
【1】 Vig, R.; Mao, C.; Venkatachalam, T.K.; Tuel-Ahlgren, L.; Sudbeck, E.A.; Uckun, F.M.; Rational design and synthesis of phenethyl-5-bromopyridyl thiourea derivatives as potent non-nucleoside inhibitors of HIV reverse transcriptase. Bioorg Med Chem 1998, 6, 10, 1789.
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) 12123 5-Bromo-2-pyridinylamine; 5-Bromo-2-pyridinamine; 2-Amino-5-bromopyridine 1072-97-5 C5H5BrN2 详情 详情
(II) 11990 Di(1H-imidazol-1-yl)methanethione; 1,1'-Thiocarbonyldiimidazole 6160-65-2 C7H6N4S 详情 详情
(III) 26465 methyl (2S,3R)-3-cyclopropyl-2,3-dihydroxypropanoate C7H12O4 详情 详情
(IV) 31335 3-chlorophenethylamine; 2-(3-chlorophenyl)-1-ethanamine 13078-79-0 C8H10ClN 详情 详情

合成路线7

该中间体在本合成路线中的序号：(I)

2-Amino-5-bromopyridine (I) was condensed with 1,1-thiocarbonyldiimidazole (II) in acetonitrile to furnish the precursor thiocarbonyl derivative (III). Further reaction of (III) with 2-fluorophenethylamine (IV) in DMF at 100 C gave the target thiourea.

参考文献 中间体
合成目标
【1】 Vig, R.; Mao, C.; Venkatachalam, T.K.; Tuel-Ahlgren, L.; Sudbeck, E.A.; Uckun, F.M.; Rational design and synthesis of phenethyl-5-bromopyridyl thiourea derivatives as potent non-nucleoside inhibitors of HIV reverse transcriptase. Bioorg Med Chem 1998, 6, 10, 1789.
【2】 Uckun, F.M. (Parker Hughes Institute); NNI for treatment of multi-drug resistant HIV. WO 0056736 .
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) 12123 5-Bromo-2-pyridinylamine; 5-Bromo-2-pyridinamine; 2-Amino-5-bromopyridine 1072-97-5 C5H5BrN2 详情 详情
(II) 11990 Di(1H-imidazol-1-yl)methanethione; 1,1'-Thiocarbonyldiimidazole 6160-65-2 C7H6N4S 详情 详情
(III) 26465 methyl (2S,3R)-3-cyclopropyl-2,3-dihydroxypropanoate C7H12O4 详情 详情
(IV) 31333 2-fluorophenethylamine; 2-(2-fluorophenyl)-1-ethanamine C8H10FN 详情 详情

合成路线8

该中间体在本合成路线中的序号：(I)

The reaction of 5-bromopyridin-2-amine (I) with thiocarbonyldiimidazole (II) in acetonitrile gives the thioamide (III), which is finally condensed with 2-(2,5-dimethoxyphenyl)ethylamine (IV) in DMF at 100 C.

参考文献 中间体
合成目标
【1】 Vig, R.; Mao, C.; Venkatachalam, T.K.; Tuel-Ahlgren, L.; Sudbeck, E.A.; Uckun, F.M.; Rational design and synthesis of phenethyl-5-bromopyridyl thiourea derivatives as potent non-nucleoside inhibitors of HIV reverse transcriptase. Bioorg Med Chem 1998, 6, 10, 1789.
【2】 Uckun, F.M. (Parker Hughes Institute); NNI for treatment of multi-drug resistant HIV. WO 0056736 .
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) 12123 5-Bromo-2-pyridinylamine; 5-Bromo-2-pyridinamine; 2-Amino-5-bromopyridine 1072-97-5 C5H5BrN2 详情 详情
(II) 11990 Di(1H-imidazol-1-yl)methanethione; 1,1'-Thiocarbonyldiimidazole 6160-65-2 C7H6N4S 详情 详情
(III) 24645 N-(5-bromo-2-pyridinyl)-1H-imidazole-1-carbothioamide C9H7BrN4S 详情 详情
(IV) 36889 2,5-dimethoxyphenethylamine; 2-(2,5-dimethoxyphenyl)-1-ethanamine 3600-86-0 C10H15NO2 详情 详情

合成路线9

该中间体在本合成路线中的序号：(I)

2-Amino-5-bromopyridine (I) was condensed with 1,1-thiocarbonyldiimidazole (II) in acetonitrile to furnish the precursor thiocarbonyl derivative (III). Further reaction of (III) with 3-fluorophenethylamine (IV) in DMF at 100 C gave the target thiourea.

参考文献 中间体
合成目标
【1】 Vig, R.; Mao, C.; Venkatachalam, T.K.; Tuel-Ahlgren, L.; Sudbeck, E.A.; Uckun, F.M.; Rational design and synthesis of phenethyl-5-bromopyridyl thiourea derivatives as potent non-nucleoside inhibitors of HIV reverse transcriptase. Bioorg Med Chem 1998, 6, 10, 1789.
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) 12123 5-Bromo-2-pyridinylamine; 5-Bromo-2-pyridinamine; 2-Amino-5-bromopyridine 1072-97-5 C5H5BrN2 详情 详情
(II) 11990 Di(1H-imidazol-1-yl)methanethione; 1,1'-Thiocarbonyldiimidazole 6160-65-2 C7H6N4S 详情 详情
(III) 26465 methyl (2S,3R)-3-cyclopropyl-2,3-dihydroxypropanoate C7H12O4 详情 详情
(IV) 31336 3-fluorophenethylamine; 2-(3-fluorophenyl)-1-ethanamine C8H10FN 详情 详情

合成路线10

该中间体在本合成路线中的序号：(XIII)

3-Fluorophenol (I) was converted into propionic ester (II) by treatment with propionyl chloride and pyridine. Fries rearrangement of (II) in the presence of AlCl3 furnished propiophenone (III). The phenolic hydroxyl group of (III) was then protected as the methyl ether (IV) using iodomethane and K2CO3. The keto group of (IV) was subsequently protected as the ethylene ketal (V) by treatment with ethylene glycol and p-toluenesulfonic acid. Lithiation of (V) with n-butyllithium in THF at -65 C, followed by formylation with N,N-dimethylformamide yielded aldehyde (VI). Styrene derivative (VII) was obtained by Wittig reaction of aldehyde (VI) with methylene triphenylphosphorane. Asymmetric cyclopropanation of (VII) with ethyl diazoacetate in the presence of cuprous triflate and the chiral auxiliary (VIII) gave the desired (1S,2R)-cis ester (IX) along with some trans isomer, that was separated by column chromatography. After ketal (IX) hydrolysis with HCl, the resulting keto ester (X) was saponified with LiOH to provide cyclopropanecarboxylic acid (XI). Curtius rearrangement of acid (XI) employing diphenylphosphoryl azide produced isocyanate (XII), which was subsequently condensed with 2-amino-5-bromopyridine (XIII) to afford urea (XIV). The methyl ether group of (XIV) was finally cleaved to the title phenol by means of boron trichloride in CH2Cl2.

参考文献 中间体
合成目标
【1】 Sahlberg, C.; Engelhardt, P.; Hogberg, M.; et al.; Urea-PETT compounds as a new class of HIV-1 reverse transcriptase inhibitors.3.Synthesis and further structure-activity relationship studies of PETT analogues. J Med Chem 1999, 42, 20, 4150.
【2】 Noreen, R.; Hogberg, M.; Engelhardt, P.; Sahlberg, C. (Medivir AB); Antivirals. WO 9936406 .
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) 23809 3-fluorophenol 372-20-3 C6H5FO 详情 详情
(II) 41992 3-fluorophenyl propionate C9H9FO2 详情 详情
(III) 41993 1-(4-fluoro-2-hydroxyphenyl)-1-propanone C9H9FO2 详情 详情
(IV) 41994 1-(4-fluoro-2-methoxyphenyl)-1-propanone C10H11FO2 详情 详情
(V) 41995 2-ethyl-2-(4-fluoro-2-methoxyphenyl)-1,3-dioxolane; 2-(2-ethyl-1,3-dioxolan-2-yl)-5-fluorophenyl methyl ether C12H15FO3 详情 详情
(VI) 41996 3-(2-ethyl-1,3-dioxolan-2-yl)-6-fluoro-2-methoxybenzaldehyde C13H15FO4 详情 详情
(VII) 41997 6-(2-ethyl-1,3-dioxolan-2-yl)-3-fluoro-2-vinylphenyl methyl ether; 2-ethyl-2-(4-fluoro-2-methoxy-3-vinylphenyl)-1,3-dioxolane C14H17FO3 详情 详情
(VIII) 41998 (4R)-4-(tert-butyl)-2-[1-[(4R)-4-(tert-butyl)-4,5-dihydro-1,3-oxazol-2-yl]-1-methylethyl]-4,5-dihydro-1,3-oxazole C17H30N2O2 详情 详情
(IX) 41999 ethyl (1S,2R)-2-[3-(2-ethyl-1,3-dioxolan-2-yl)-6-fluoro-2-methoxyphenyl]cyclopropanecarboxylate C18H23FO5 详情 详情
(X) 42000 ethyl (1S,2R)-2-(6-fluoro-2-methoxy-3-propionylphenyl)cyclopropanecarboxylate C16H19FO4 详情 详情
(XI) 42001 (1S,2R)-2-(6-fluoro-2-methoxy-3-propionylphenyl)cyclopropanecarboxylic acid C14H15FO4 详情 详情
(XII) 42002 1-[4-fluoro-3-[(1S,2S)-2-isocyanatocyclopropyl]-2-methoxyphenyl]-1-propanone C14H14FNO3 详情 详情
(XIII) 12123 5-Bromo-2-pyridinylamine; 5-Bromo-2-pyridinamine; 2-Amino-5-bromopyridine 1072-97-5 C5H5BrN2 详情 详情
(XIV) 42003 N-(5-bromo-2-pyridinyl)-N'-[(1S,2S)-2-(6-fluoro-2-methoxy-3-propionylphenyl)cyclopropyl]urea C19H19BrFN3O3 详情 详情

合成路线11

该中间体在本合成路线中的序号：(I)

Treatment of 2-amino-5-bromopyridine (I) with 2-(1-cyclohexenyl)ethyl isothiocyanate (II) in hot N-methylpyrrolidinone produced the target thiourea.

参考文献 中间体
合成目标
【1】 Lind, P.T.; Noreen, R.; Ternansky, R.J.; Morin, J.M. Jr. (Medivir AB); Cpds. and methods for inhibition of HIV and related viruses. WO 9303022 .
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) 12123 5-Bromo-2-pyridinylamine; 5-Bromo-2-pyridinamine; 2-Amino-5-bromopyridine 1072-97-5 C5H5BrN2 详情 详情
(II) 36901 2-(1-cyclohexen-1-yl)ethyl isothiocyanate; 1-(2-isothiocyanatoethyl)-1-cyclohexene C9H13NS 详情 详情

合成路线12

该中间体在本合成路线中的序号：(I)

Alternatively, 2-amino-5-bromopyridine (I) was reacted with 1,1'-thiocarbonyldiimidazole (III) in acetonitrile yielding thioimidazolide (IV), which was then condensed with 2-(1-cyclohexenyl)ethylamine (V) in hot DMF.

参考文献 中间体
合成目标
【1】 Maher, D.; Mao, C.; Pendergrass, S.; Venkatachalam, T.K.; Zhu, D.; Tuel-Ahlgren, L.; Uckun, F.M.; N-[2-(1-Cyclohexenyl)ethyl]-N'-[2-(5-bromopyridyl)]-thiourea and N'-[2-(1-cyclohexenyl)ethyl]-N'-[2-(5-chloropyridyl)]-thiourea as potent inhibitors of multidrug-resistant human immunodeficiency virus-1. Bioorg Med Chem Lett 1999, 9, 18, 2721.
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) 12123 5-Bromo-2-pyridinylamine; 5-Bromo-2-pyridinamine; 2-Amino-5-bromopyridine 1072-97-5 C5H5BrN2 详情 详情
(III) 11990 Di(1H-imidazol-1-yl)methanethione; 1,1'-Thiocarbonyldiimidazole 6160-65-2 C7H6N4S 详情 详情
(IV) 24645 N-(5-bromo-2-pyridinyl)-1H-imidazole-1-carbothioamide C9H7BrN4S 详情 详情
(V) 36902 2-(1-cyclohexen-1-yl)ethylamine; 2-(1-cyclohexen-1-yl)-1-ethanamine; 2-(1-Cyclohexenyl)ethylamine 3399-73-3 C8H15N 详情 详情

合成路线13

该中间体在本合成路线中的序号：(I)

Reaction of 2-amino-5-bromopyridine (I) with thiocarbonyl diimidazole (II) provided the thioimidazolide (III). This was then coupled with 2-(2-thienyl)ethyl amine (IV) to furnish the target thiourea.

参考文献 中间体
合成目标
【1】 Maher, D.; Mao, C.; Tuel-Ahlgren, L.; Uckun, F.M.; Zhu, D.; Pendergrass, S.; Venkatachalam, T.K.; N'-[2-(2-Thiophene)ethyl]-N'-[2-(5-bromopyridyl)] thiourea as a potent inhibitor of NNI-resistant and multidrug-resistant human immunodeficiency virus-1. Bioorg Med Chem Lett 1999, 9, 24, 3411.
【2】 Ventatachalam, T.K.; Uckun, F.M. (Parker Hughes Institute); Thiophene-ethyl thiourea cpds. and use. US 6124324; WO 0078755 .
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) 12123 5-Bromo-2-pyridinylamine; 5-Bromo-2-pyridinamine; 2-Amino-5-bromopyridine 1072-97-5 C5H5BrN2 详情 详情
(II) 11990 Di(1H-imidazol-1-yl)methanethione; 1,1'-Thiocarbonyldiimidazole 6160-65-2 C7H6N4S 详情 详情
(III) 24645 N-(5-bromo-2-pyridinyl)-1H-imidazole-1-carbothioamide C9H7BrN4S 详情 详情
(IV) 35253 2-(2-thienyl)ethylamine; 2-(2-thienyl)-1-ethanamine; 2-Thiophene ethylamine 30433-91-1 C6H9NS 详情 详情

合成路线14

该中间体在本合成路线中的序号：(I)

Reaction of 2-amino-5-bromopyridine (I) with thiocarbonyldiimidazole (II) afforded the thioimidazolide (III). This was then condensed with 4-methylphenetylamine (IV) in hot DMF to produce the required thiourea.

参考文献 中间体
合成目标
【2】 Ventalachalam, T.K.; Uckum, F.M. (Parker Hughes Institute); Phenethyl-thiourea cpds. and use. US 6207688 .
【1】 Uckun, F.M.; Zhu, D.; Pendergrass, S.; Mao, C.; Tuel-Ahlgren, L.; Venkatachalam, T.K.; Maher, D.; N-[2-(4-Methylphenyl)ethyl]-N'-[2-(5-bromopyridyl)]thiourea as a potent inhibitor of NNRTI-resistant and multidrug-resistant human immunodeficiency virus type 1. Antivir Chem Chemother 2000, 11, 2, 135.
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) 12123 5-Bromo-2-pyridinylamine; 5-Bromo-2-pyridinamine; 2-Amino-5-bromopyridine 1072-97-5 C5H5BrN2 详情 详情
(II) 11990 Di(1H-imidazol-1-yl)methanethione; 1,1'-Thiocarbonyldiimidazole 6160-65-2 C7H6N4S 详情 详情
(III) 24645 N-(5-bromo-2-pyridinyl)-1H-imidazole-1-carbothioamide C9H7BrN4S 详情 详情
(IV) 46291 4-methylphenethylamine; 2-(4-methylphenyl)-1-ethanamine C9H13N 详情 详情

合成路线15

该中间体在本合成路线中的序号：(I)

Condensation of 2-amino-5-bromopyridine (I) with thiocarbonyl diimidazole (II) gave rise to thioimidazolide (III), which was then condensed with (R)-1-phenylethylamine (IV) to yield the title thiourea.

参考文献 中间体
合成目标
【1】 Mao, C.; Venkatachalam, T.K.; Uckun, F.M.; Sudbeck, E.A.; Stereochemistry of halopyridyl and thiazolyl thiourea compounds is a major determinant of their potency as nonnucleoside inhibitors of HIV-1 reverse transcriptase. Bioorg Med Chem Lett 2000, 10, 18, 2071.
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) 12123 5-Bromo-2-pyridinylamine; 5-Bromo-2-pyridinamine; 2-Amino-5-bromopyridine 1072-97-5 C5H5BrN2 详情 详情
(II) 11990 Di(1H-imidazol-1-yl)methanethione; 1,1'-Thiocarbonyldiimidazole 6160-65-2 C7H6N4S 详情 详情
(III) 24645 N-(5-bromo-2-pyridinyl)-1H-imidazole-1-carbothioamide C9H7BrN4S 详情 详情
(IV) 10039 (1R)-1-Phenylethylamine; (1R)-1-Phenyl-1-ethanamine.; L-alpha-Phenylethylamine 3886-69-9 C8H11N 详情 详情

合成路线16

该中间体在本合成路线中的序号：(II)

Condensation between 2-bromo-4'-(dimethylamino)acetophenone (I) and 2-amino-5-bromopyridine (II) gives rise to the imidazopyridine (III). Subsequent palladium-catalyzed stannylation of (III) affords the tributyltin derivative (IV). The target radio-iodinated compound is then obtained by iododstannylation of (IV) with [125I] iodide in the presence of H2O2 (1,2)

参考文献 中间体
合成目标
【1】 Zhuang, Z.-P.; Kung, M.-P.; Wilson, A.; Lee, C.-W.; Plossl, K.; Hou, C.; Holtzman, D.M.; Kung, H.F.; Structure-activity relationship of imidazo[1,2-a]pyridines as ligands for detecting beta-amyloid plaques in the brain. J Med Chem 2003, 46, 2, 237.
【2】 Kung, H.; Kung, M.-P.; Zhuang, Z.-P. (University of Pennsylvania); Amyloid plaque aggregation inhibitors and diagnostic imaging agents. CA 2444214; EP 1381604; US 2003059369; WO 0285903 .
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) 63545 2-bromo-1-[4-(dimethylamino)phenyl]-1-ethanone C10H12BrNO 详情 详情
(II) 12123 5-Bromo-2-pyridinylamine; 5-Bromo-2-pyridinamine; 2-Amino-5-bromopyridine 1072-97-5 C5H5BrN2 详情 详情
(III) 63546 4-(6-bromoimidazo[1,2-a]pyridin-2-yl)-N,N-dimethylaniline; N-[4-(6-bromoimidazo[1,2-a]pyridin-2-yl)phenyl]-N,N-dimethylamine C15H14BrN3 详情 详情
(IV) 63547 N,N-dimethyl-4-[6-(tributylstannyl)imidazo[1,2-a]pyridin-2-yl]aniline; N,N-dimethyl-N-{4-[6-(tributylstannyl)imidazo[1,2-a]pyridin-2-yl]phenyl}amine C27H41N3Sn 详情 详情
Extended Information