Hydrochloric Acid → ethyl 4-[2-chloro-5-(3,4-dihydroquinolin-1(2H)-yl sulfonyl)phenylamino]pyrimidine-5-carboxylate

HRID 1513038ノート

反応式

HRID 1513038 の反応式
Cl[C:2]1[C:7]([C:8]([O:10][CH2:11][CH3:12])=[O:9])=[CH:6][N:5]=[CH:4][N:3]=1.[Cl:13][C:14]1[CH:20]=[CH:19][C:18]([S:21]([N:24]2[C:33]3[C:28](=[CH:29][CH:30]=[CH:31][CH:32]=3)[CH2:27][CH2:26][CH2:25]2)(=[O:23])=[O:22])=[CH:17][C:15]=1[NH2:16].[H-].[Na+].Cl>CN1CCCC1=O>[Cl:13][C:14]1[CH:20]=[CH:19][C:18]([S:21]([N:24]2[C:33]3[C:28](=[CH:29][CH:30]=[CH:31][CH:32]=3)[CH2:27][CH2:26][CH2:25]2)(=[O:22])=[O:23])=[CH:17][C:15]=1[NH:16][C:2]1[C:7]([C:8]([O:10][CH2:11][CH3:12])=[O:9])=[CH:6][N:5]=[CH:4][N:3]=1

参加物

6

反応物 4

HCID 313Hydrochloric AcidHCID 24758Sodium hydrideHCID 12684326Ethyl 4-chloropyrimidine-5-carboxylateHCID 231200411-(3-Amino-4-chlorobenzenesulfonyl)-1,2,3,4-tetrahydroquinoline

生成物 1

HCID 68514819ethyl 4-[2-chloro-5-(3,4-dihydroquinolin-1(2H)-yl sulfonyl)phenylamino]pyrimidine-5-carboxylate収率 41.5%

試薬・触媒・溶媒 1

HCID 13387N-methyl-2-pyrrolidone溶媒

反応条件

温度
100 °C

実験手順

A mixture of ethyl 4-chloropyrimidine-5-carboxylate (0.4 g), 2-chloro-5-(3,4-dihydroquinolin-1(2H)-ylsulfonyl)aniline (0.69 g) and sodium hydride (55%, 98 mg) in 1-methyl-2-pyrrolidone (8 mL) was stirred at 100° C. for 2 hours. The reaction mixture was poured into 0.5 mol/L hydrochloric acid, and the resulting mixture was extracted with ethyl acetate. The extract was washed with water and brine, and dried over anhydrous magnesium sulfate. The solvent was removed under reduced pressure, and the residue was purified by column chromatography on silica gel (eluent: n-hexane/ethyl acetate=3/1−2/1) to give ethyl 4-[2-chloro-5-(3,4-dihydroquinolin-1(2H)-yl sulfonyl)phenylamino]pyrimidine-5-carboxylate (0.42 g). To this material were added ethanol (8 mL), tetrahydrofuran (2 mL) and 5 mol/L aqueous sodium hydroxide solution (1.77 mL), and the mixture was stirred at room temperature for 3 days. The reaction mixture was acidified by adding 1 mol/L hydrochloric acid, and the precipitated crystals were collected by filtration. The crystals were washed with water, and dried under reduced pressure to give 4-[2-chloro-5-(3,4-dihydroquinolin-1(2H)-ylsulfonyl)phenylamino]pyrimidine-5-carboxylic acid (0.37 g). The obtained 4-[2-chloro-5-(3,4-dihydroquinolin-1(2H)-ylsulfonyl)phenylamino]pyrimidine-5-carboxylic acid (0.1 g) was dissolved in 1,4-dioxane (2 mL). To the solution were added triethylamine (0.094 mL) and diphenylphosphoryl azide (0.058 mL), and the mixture was stirred at 100° C. for 3 hours. The reaction mixture was poured into water, and the resulting mixture was extracted with ethyl acetate. The extract was washed with water and brine, and dried over anhydrous magnesium sulfate. The solvent was removed under reduced pressure, and the residue was purified by column chromatography on silica gel (eluent: n-hexane/ethyl acetate=1/2−ethyl acetate) to give the title compound (80 mg).

後処理

  1. extractionthe resulting mixture was extracted with ethyl acetate
  2. washThe extract was washed with water and brine
  3. dry with materialdried over anhydrous magnesium sulfate
  4. customThe solvent was removed under reduced pressure
  5. customthe residue was purified by column chromatography on silica gel (eluent: n-hexane/ethyl acetate=3/1−2/1)

出典と根拠

ORDレコード
ord-ba56537c00ac4e76862af8322923ac2e
出典データセット
uspto-grants-2012_07
特許番号
US08217069B2

反応ノート

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