6-Bromonicotinic acid → HCID 58484741、化合物

HRID 1804090ノート

反応式

HRID 1804090 の反応式
[Br:1][C:2]1[CH:10]=[CH:9][C:5]([C:6]([OH:8])=O)=[CH:4][N:3]=1.[CH:11]1([C:14]2[CH:19]=[C:18]([CH:20]3[CH2:22][CH2:21]3)[CH:17]=[CH:16][C:15]=2[N:23]2[CH2:28][CH2:27][NH:26][CH2:25][CH2:24]2)[CH2:13][CH2:12]1>>[Br:1][C:2]1[N:3]=[CH:4][C:5]([C:6]([N:26]2[CH2:27][CH2:28][N:23]([C:15]3[CH:16]=[CH:17][C:18]([CH:20]4[CH2:21][CH2:22]4)=[CH:19][C:14]=3[CH:11]3[CH2:13][CH2:12]3)[CH2:24][CH2:25]2)=[O:8])=[CH:9][CH:10]=1

参加物

3

反応物 2

HCID 2389326-Bromonicotinic acidHCID 67381204HCID 67381204、化合物

生成物 1

HCID 58484741HCID 58484741、化合物収率 100%

実験手順

A mixture of 1-(2,4-dichlorophenyl)piperazine (3 g), di-tert-butyl dicarbonate (3.23 g), triethylamine (5.5 mL) and methanol (30 mL) was stirred at room temperature for 5 hr. Water and ethyl acetate were added for partitioning, the organic layer was washed with saturated brine, and the solvent was evaporated. The residue was purified by column chromatography (hexane:ethyl acetate) to give 4-(2,4-dichlorophenyl)piperazine-1-carboxylic acid tert-butyl ester (3.3 g). To a solution of 4-(2,4-dichlorophenyl)piperazine-1-carboxylic acid tert-butyl ester (3.3 g) in tetrahydrofuran (15 mL) were added 2-dicyclohexylphosphino-2′,6′-dimethoxybiphenyl (809 mg), palladium acetate (442 mg), tripotassium phosphate (11 g) and cyclopropylboronic acid (2.54 g), and the mixture was refluxed for 7 hr. After cooling, the mixture was extracted with ethyl acetate, washed with saturated brine, and the solvent was evaporated. The residue was purified by column chromatography (hexane:ethyl acetate) to give 4-(2,4-dicyclopropylphenyl)piperazine-1-carboxylic acid tert-butyl ester (3.3 g). 4-(2,4-Dicyclopropylphenyl)piperazine-1-carboxylic acid tert-butyl ester (3.3 g) was dissolved in dichloromethane (20 mL), 4N hydrogen chloride/dioxane (10 mL) was added, and the mixture was stirred at room temperature for 3.5 hr. Diethyl ether (100 mL) was added, and the precipitate was collected by filtration. To the obtained precipitate were added ethyl acetate and 1N aqueous sodium hydroxide solution, and the mixture was extracted with ethyl acetate and washed with saturated brine. The solvent was evaporated to give 1-(2,4-dicyclopropylphenyl)piperazine (1.6 g). By reaction and treatment in the same manner as in Preparation Example 27 and using 6-bromonicotinic acid (237 mg) and 1-(2,4-dicyclopropylphenyl)piperazine (300 mg), the title compound (500 mg) was obtained.

後処理

  1. customBy reaction and treatment in the same manner
  2. customas in Preparation Example 27

出典と根拠

ORDレコード
ord-b70abf4b36354f9fa9e896ab60d55682
出典データセット
uspto-grants-2013_01
特許番号
US08354401B2

反応ノート

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