Sodium hydride → 4-(tert-butyl)-N-[3-{2-[(5-fluoro-2-pyrimidinyl)oxy]ethoxy}-1-methyl-4-(4-methylphenyl)-1H-pyrazol-5-yl]benzenesulfonamide

HRID 1368588ノート

反応式

HRID 1368588 の反応式
[C:1]([C:5]1[CH:10]=[CH:9][C:8]([S:11]([NH:14][C:15]2[N:19]([CH3:20])[N:18]=[C:17]([O:21][CH2:22][CH2:23][OH:24])[C:16]=2[C:25]2[CH:30]=[CH:29][C:28]([CH3:31])=[CH:27][CH:26]=2)(=[O:13])=[O:12])=[CH:7][CH:6]=1)([CH3:4])([CH3:3])[CH3:2].[H-].[Na+].Cl[C:35]1[N:40]=[CH:39][C:38]([F:41])=[CH:37][N:36]=1.[Cl-].[NH4+]>O1CCCC1.CC(N(C)C)=O.C(OCC)(=O)C>[C:1]([C:5]1[CH:6]=[CH:7][C:8]([S:11]([NH:14][C:15]2[N:19]([CH3:20])[N:18]=[C:17]([O:21][CH2:22][CH2:23][O:24][C:35]3[N:40]=[CH:39][C:38]([F:41])=[CH:37][N:36]=3)[C:16]=2[C:25]2[CH:30]=[CH:29][C:28]([CH3:31])=[CH:27][CH:26]=2)(=[O:12])=[O:13])=[CH:9][CH:10]=1)([CH3:4])([CH3:3])[CH3:2]

参加物

8

反応物 4

HCID 24758Sodium hydrideHCID 25517Ammonium ChlorideHCID 5834662-Chloro-5-fluoropyrimidineHCID 222820434-(tert-butyl)-N-[3-(2-hydroxyethoxy)-1-methyl-4-(4-methylphenyl)-1H-pyrazol-5-yl]benzenesulfonamide

生成物 1

HCID 222819924-(tert-butyl)-N-[3-{2-[(5-fluoro-2-pyrimidinyl)oxy]ethoxy}-1-methyl-4-(4-methylphenyl)-1H-pyrazol-5-yl]benzenesulfonamide収率 12.4%

試薬・触媒・溶媒 3

HCID 8028Tetrahydrofuran溶媒HCID 8857Ethyl Acetate溶媒HCID 31374Dimethylacetamide溶媒

実験手順

To 4-(tert-butyl)-N-[3-(2-hydroxyethoxy)-1-methyl-4-(4-methylphenyl)-1H-pyrazol-5-yl]benzenesulfonamide (Example 2, 126 mg) in tetrahydrofuran (5 ml) at room temperature under an atmosphere of nitrogen was added sodium hydride (60% dispersion in oil, 34 mg) and the reaction mixture was stirred for 5 minutes. To the reaction mixture was added a solution of 2-chloro-5-fluoropyrimidine (50 mg) in dimethyl acetamide (1 ml) and the reaction was stirred for a further 16 hours. The reaction was poured cautiously into a stirred mixture of saturated aqueous ammonium chloride solution (10 ml) and ethyl acetate (10 ml). The organic fraction was separated, dried over magnesium sulphate, filtered and concentrated under reduced pressure. The residue was purified by preparative HPLC on a 5μ ODS Phenomenex Magellen™ column with gradient elution of acetonitrile (5% to 95%) and 0.1M NH4OAc (95% to 5%) to yield the title compound as a white solid (19 mg).

後処理

  1. stirringthe reaction was stirred for a further 16 hours
  2. customThe organic fraction was separated
  3. dry with materialdried over magnesium sulphate
  4. filtrationfiltered
  5. concentrationconcentrated under reduced pressure
  6. customThe residue was purified by preparative HPLC on a 5μ ODS Phenomenex Magellen™ column with gradient elution of acetonitrile (5% to 95%) and 0.1M NH4OAc (95% to 5%)

出典と根拠

ORDレコード
ord-dacec9378b374855bfed9fbc6fe518fa
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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