Citric Acid → N-[3-{2-[(5-chloropyrimidin-2-yl)oxy]ethoxy}-1-methyl-4-(4-methylphenyl)-1H-pyrazol-5-yl]-5-methylpyridine-2-sulphonamide

HRID 1368599ノート

反応式

HRID 1368599 の反応式
[OH:1][CH2:2][CH2:3][O:4][C:5]1[C:9]([C:10]2[CH:15]=[CH:14][C:13]([CH3:16])=[CH:12][CH:11]=2)=[C:8]([NH:17][S:18]([C:21]2[CH:26]=[CH:25][C:24]([CH3:27])=[CH:23][N:22]=2)(=[O:20])=[O:19])[N:7]([CH3:28])[N:6]=1.[H-].[Na+].[Cl:31][C:32]1[CH:33]=[N:34][C:35](S(C)(=O)=O)=[N:36][CH:37]=1.C(O)(=O)CC(CC(O)=O)(C(O)=O)O>O1CCCC1>[Cl:31][C:32]1[CH:33]=[N:34][C:35]([O:1][CH2:2][CH2:3][O:4][C:5]2[C:9]([C:10]3[CH:15]=[CH:14][C:13]([CH3:16])=[CH:12][CH:11]=3)=[C:8]([NH:17][S:18]([C:21]3[CH:26]=[CH:25][C:24]([CH3:27])=[CH:23][N:22]=3)(=[O:19])=[O:20])[N:7]([CH3:28])[N:6]=2)=[N:36][CH:37]=1

参加物

6

反応物 4

HCID 311Citric AcidHCID 24758Sodium hydride2 回HCID 27277255-Chloro-2-methanesulfonylpyrimidine2 回HCID 22281909N-[3-(2-hydroxyethoxy)-1-methyl-4-(4-methylphenyl)-1H-pyrazol-5-yl]-5-methylpyridine-2-sulphonamide

生成物 1

HCID 22282045N-[3-{2-[(5-chloropyrimidin-2-yl)oxy]ethoxy}-1-methyl-4-(4-methylphenyl)-1H-pyrazol-5-yl]-5-methylpyridine-2-sulphonamide収率 78.9%

試薬・触媒・溶媒 1

HCID 8028Tetrahydrofuran溶媒2 回

実験手順

To N-[3-(2-hydroxyethoxy)-1-methyl-4-(4-methylphenyl)-1H-pyrazol-5-yl]-2-pyridine sulphonamide (Example 50) (100 mg) in dry tetrahydrofuran (5 ml) at room temperature was added sodium hydride (80% dispersion in oil, 20 mg) the mixture was stirred for 20 minutes. A solution of 5-chloro-2-methylsulphonylpyrimidine (72 mg) in dry tetrahydrofuran (2.5 ml) was then added and the mixture was stirred for a further 16 hours. The mixture was then treated with further sodium hydride (80% dispersion in oil, 20 mg) and after 15 minutes stirring further 5-chloro-2-methylsulphonylpyrimidine (84 mg) was also added. The mixture was stirred for 4 hours. The reaction was treated with citric acid (10% aq.) and extracted with ethyl acetate (50 ml). The organic fraction was washed with brine (50 ml), dried over magnesium sulfate, filtered and concentrated under reduced pressure. The residue was purified by column chromatography on silica (10 g) eluted with a solvent gradient of pentane:ethyl acetate (8:2 to 0:1) to yield the tile compound as a yellow solid (101 mg).

後処理

  1. stirringthe mixture was stirred for a further 16 hours
  2. additionwas also added
  3. stirringThe mixture was stirred for 4 hours
  4. extractionextracted with ethyl acetate (50 ml)
  5. washThe organic fraction was washed with brine (50 ml)
  6. dry with materialdried over magnesium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated under reduced pressure
  9. customThe residue was purified by column chromatography on silica (10 g)
  10. washeluted with a solvent gradient of pentane:ethyl acetate (8:2 to 0:1)

出典と根拠

ORDレコード
ord-8313f680b7d4461fa60539a16336b898
出典データセット
uspto-grants-2003_06
特許番号
US06573270B1

反応ノート

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