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 1368650노트

반응식

HRID 1368650 반응식
[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]

참가 물질

8

반응물 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

생성물 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]benzenesulfonamide수율 71.9%

시약·촉매·용매 3

HCID 3283Diethyl Ether용매HCID 6228Dimethylformamide용매HCID 8028Tetrahydrofuran용매

실험 절차

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).

후처리

  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

출처 및 근거

ORD 기록
ord-dc272c57d25c4c76a422e593d49ec019
출처 데이터셋
uspto-grants-2003_06
특허 번호
US06573270B1

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