Citric Acid → 4-(tert-butyl)-N-[1-(2-{[tert-butyl(dimethyl)silyl]oxy}ethyl)-3-(2-[{5-chloro-2-pyrimidinyl}oxy]ethoxy)-4-(4-methylphenyl)-1H-pyrazol-5-yl]benzenesulfonamide

HRID 1368650ノート

反応式

HRID 1368650 の反応式
[H-].[Na+].[C:3]([C:7]1[CH:12]=[CH:11][C:10]([S:13]([NH:16][C:17]2[N:21]([CH2:22][CH2:23][O:24][Si:25]([C:28]([CH3:31])([CH3:30])[CH3:29])([CH3:27])[CH3:26])[N:20]=[C:19]([O:32][CH2:33][CH2:34][OH:35])[C:18]=2[C:36]2[CH:41]=[CH:40][C:39]([CH3:42])=[CH:38][CH:37]=2)(=[O:15])=[O:14])=[CH:9][CH:8]=1)([CH3:6])([CH3:5])[CH3:4].[Cl:43][C:44]1[CH:45]=[N:46][C:47](S(C)(=O)=O)=[N:48][CH:49]=1.C(O)(=O)CC(CC(O)=O)(C(O)=O)O>C1COCC1.CCOCC.CN(C=O)C>[C:3]([C:7]1[CH:8]=[CH:9][C:10]([S:13]([NH:16][C:17]2[N:21]([CH2:22][CH2:23][O:24][Si:25]([C:28]([CH3:31])([CH3:30])[CH3:29])([CH3:27])[CH3:26])[N:20]=[C:19]([O:32][CH2:33][CH2:34][O:35][C:47]3[N:48]=[CH:49][C:44]([Cl:43])=[CH:45][N:46]=3)[C:18]=2[C:36]2[CH:37]=[CH:38][C:39]([CH3:42])=[CH:40][CH:41]=2)(=[O:14])=[O:15])=[CH:11][CH:12]=1)([CH3:4])([CH3:5])[CH3:6]

参加物

8

反応物 4

HCID 311Citric AcidHCID 24758Sodium hydrideHCID 27277255-Chloro-2-methanesulfonylpyrimidineHCID 234003144-(tert-butyl)-N-[1-(2-{[tert-butyl(dimethyl)silyl]oxy}ethyl)-3-(2-hydroxyethoxy)-4-(4-methylphenyl)-1H-pyrazol-5-yl]benzenesulfonamide

生成物 1

HCID 234003224-(tert-butyl)-N-[1-(2-{[tert-butyl(dimethyl)silyl]oxy}ethyl)-3-(2-[{5-chloro-2-pyrimidinyl}oxy]ethoxy)-4-(4-methylphenyl)-1H-pyrazol-5-yl]benzenesulfonamide収率 71.9%

試薬・触媒・溶媒 3

HCID 3283Diethyl Ether溶媒HCID 6228Dimethylformamide溶媒HCID 8028Tetrahydrofuran溶媒

実験手順

Sodium hydride (16 mg, 60% suspension in mineral oil) was added to a stirred solution of 4-(tert-butyl)-N-[1-(2-{[tert-butyl(dimethyl)silyl]oxy}ethyl)-3-(2-hydroxyethoxy)-4-(4-methylphenyl)-1H-pyrazol-5-yl]benzenesulfonamide (105 mg) (Preparation 28) in anhydrous THF (5 ml) at room temperature under a nitrogen atmosphere and the resulting mixture was stirred for 10 minutes at room temperature. DMF (2 ml) was added to the reaction mixture, followed by 5-chloro-2-(methylsulphonyl)pyrimidine (39 mg) and the resulting mixture was stirred at room temperature overnight. The reaction mixture was poured into an aqueous solution of 1.0M citric acid (50 ml) and ether (50 ml) and the aqueous phase was separated. The organic phase was washed with water (30 ml) and then dried over magnesium sulfate, filtered and concentrated under pressure. The orange/brown residue was purified by chromatography on a Biotage Flash 12i cartridge at 10 psi using 20% ethyl acetate/hexane as eluant to give the title compound as a pale yellow oil (90 mg).

後処理

  1. stirringthe resulting mixture was stirred at room temperature overnight
  2. customthe aqueous phase was separated
  3. washThe organic phase was washed with water (30 ml)
  4. dry with materialdried over magnesium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated under pressure
  7. customThe orange/brown residue was purified by chromatography on a Biotage Flash 12i cartridge at 10 psi

出典と根拠

ORDレコード
ord-dc272c57d25c4c76a422e593d49ec019
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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