Sodium hydride → N-[3-{2-[(5-bromo-2-pyrimidinyl)oxy]ethoxy}-1-methyl-4-(4-methylphenyl)-1H-pyrazol-5-yl]-5-isopropyl-2-pyridinesulfonamide

HRID 1368594ノート

反応式

HRID 1368594 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]([CH:27]([CH3:29])[CH3:28])=[CH:23][N:22]=2)(=[O:20])=[O:19])[N:7]([CH3:30])[N:6]=1.[H-].[Na+].[Br:33][C:34]1[CH:35]=[N:36][C:37](Cl)=[N:38][CH:39]=1>C1COCC1.CC(N(C)C)=O>[Br:33][C:34]1[CH:35]=[N:36][C:37]([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]([CH:27]([CH3:28])[CH3:29])=[CH:23][N:22]=3)(=[O:19])=[O:20])[N:7]([CH3:30])[N:6]=2)=[N:38][CH:39]=1

参加物

6

反応物 3

HCID 24758Sodium hydrideHCID 6066655-Bromo-2-chloropyrimidineHCID 22282040N-[3-(2-hydroxyethoxy)-1-methyl-4-(4-methylphenyl)-1H-pyrazol-5-yl]-5-isopropyl-2-pyridinesulfonamide

生成物 1

HCID 9829887N-[3-{2-[(5-bromo-2-pyrimidinyl)oxy]ethoxy}-1-methyl-4-(4-methylphenyl)-1H-pyrazol-5-yl]-5-isopropyl-2-pyridinesulfonamide収率 45.8%

試薬・触媒・溶媒 2

HCID 8028Tetrahydrofuran溶媒HCID 31374Dimethylacetamide溶媒

実験手順

To a solution of N-[3-(2-hydroxyethoxy)-1-methyl-4-(4-methylphenyl)-1H-pyrazol-5-yl]-5-isopropyl-2-pyridinesulfonamide (Example 40) (1.00 g) in anhydrous THF (10 ml) at 0° C. and under an atmosphere of nitrogen was added sodium hydride (60% dispersion in oil, 195 mg) and the mixture was stirred for 5 minutes. To the mixture was added 5-bromo-2-chloropyrimidine (Liquid Crystals, 1993, 14(3), 741) (1.12 g) in dimethylacetamide (3 ml). After stirring for 1 hr, the reaction mixture was partitioned between ethyl acetate (100 ml) and saturated ammonium chloride solution (100 ml). The organic fraction was washed with brine (100 ml), followed by drying over magnesium sulfate, filtering and concentration under reduced pressure. Purification of the residue by preparative HPLC on a Phenomenex Magellen column using a 0.1M ammonium acetate:acetonitrile gradient (95:5 to 50:50 over 5 minutes) afforded the title compound as a white solid (625 mg).

後処理

  1. stirringAfter stirring for 1 hr
  2. customthe reaction mixture was partitioned between ethyl acetate (100 ml) and saturated ammonium chloride solution (100 ml)
  3. washThe organic fraction was washed with brine (100 ml)
  4. dry with materialby drying over magnesium sulfate
  5. filtrationfiltering
  6. concentrationconcentration under reduced pressure
  7. customPurification of the residue by preparative HPLC on a Phenomenex Magellen column

出典と根拠

ORDレコード
ord-faffc185120f428a9e3a7ee6e95d6aa3
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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