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Potassium Carbonate → N-[1-{[4-(Aminosulfonyl)phenyl]methyl}-4-(methyloxy)-1H-indazol-3-yl]-5-chloro-2-thiophenesulfonamide

HRID 1874714
ノート
印刷プレビュー

反応式

HRID 1874714 の反応式
[Cl:1][C:2]1[S:6][C:5]([S:7]([N:10]([C:19]2[C:27]3[C:22](=[CH:23][CH:24]=[CH:25][C:26]=3[O:28][CH3:29])[NH:21][N:20]=2)COCC[Si](C)(C)C)(=[O:9])=[O:8])=[CH:4][CH:3]=1.Br[CH2:31][C:32]1[CH:37]=[CH:36][C:35]([S:38]([NH2:41])(=[O:40])=[O:39])=[CH:34][CH:33]=1.C(=O)([O-])[O-].[K+].[K+]>CN(C=O)C>[NH2:41][S:38]([C:35]1[CH:36]=[CH:37][C:32]([CH2:31][N:21]2[C:22]3[C:27](=[C:26]([O:28][CH3:29])[CH:25]=[CH:24][CH:23]=3)[C:19]([NH:10][S:7]([C:5]3[S:6][C:2]([Cl:1])=[CH:3][CH:4]=3)(=[O:9])=[O:8])=[N:20]2)=[CH:33][CH:34]=1)(=[O:39])=[O:40]
参加物実験手順後処理出典と根拠反応ノート

参加物

5

反応物 3

HCID 11430Potassium Carbonate2 回HCID 131545004-BromomethylbenzenesulfonamideHCID 580544435-chloro-N-[4-(methyloxy)-1H-indazol-3-yl]-N-({[2-(trimethylsilyl)ethyl]oxy}methyl)-2-thiophenesulfonamide2 回

生成物 1

HCID 59456048N-[1-{[4-(Aminosulfonyl)phenyl]methyl}-4-(methyloxy)-1H-indazol-3-yl]-5-chloro-2-thiophenesulfonamide収率 10%

試薬・触媒・溶媒 1

HCID 6228
Dimethylformamide
溶媒

実験手順

5-Chloro-N-[4-(methyloxy)-1H-indazol-3-yl]-N-({[2-(trimethylsilyl)ethyl]oxy}methyl)-2-thiophenesulfonamide (for a preparation see Intermediate 8) (1.734 g, 3.66 mmol) was dissolved in DMF (2.4 mL) and an aliquot (0.1 mL, 0.15 mmol) added to 4-(bromomethyl)benzenesulfonamide (APAC Pharm) (0.15 mmol) and potassium carbonate (0.15 mmol) added last. The tubes were capped and shaken. Stood at room temperature for 18 h, more potassium carbonate (excess) added and reshaken the tubes. Filtered through alltech tube to remove inorganic solids, and washed tubes with MeOH (1 mL) and blown to dryness under a stream of nitrogen in a Radley's blow down unit. Redissolved in DCM (0.5 mL) and applied to a 10 g silica cartridge, and purified by chromatography on Flashmaster using a gradient of 0-100% DCM-(DCM with 20% EtOAc) over 20 min. The appropriate fractions were combined and evaporated in vacuo using the Genevac. The residue was dissolved in TBAF (1M, 0.5 mL) and heated in a microwave oven (50 Watts, 10 min, at approx 110° C. The sample was purified by MDAP on Atlantis column using Acetonitrile Water with a Formic acid modifier. The solvent was evaporated in vacuo using the Genevac to give the title compound (7.9 mg, 10%) LCMS (System A) RT=0.92 min, ES+ve m/z 513/515 (M+H)+

後処理

  1. additionadded last
  2. customThe tubes were capped
  3. filtrationFiltered through alltech tube
  4. customto remove inorganic solids
  5. washwashed tubes with MeOH (1 mL)
  6. dissolutionRedissolved in DCM (0.5 mL)
  7. custompurified by chromatography on Flashmaster
  8. customover 20 min
  9. customevaporated in vacuo
  10. dissolutionThe residue was dissolved in TBAF (1M, 0.5 mL)
  11. temperatureheated in a microwave oven (50 Watts, 10 min
  12. customat approx 110° C
  13. customThe sample was purified by MDAP on Atlantis column
  14. customThe solvent was evaporated in vacuo

出典と根拠

ORDレコード
ord-ed065d8e36804dfb94c5add9154e6974
出典データセット
uspto-grants-2012_11
DOI
10.6084/m9.figshare.5104873.v1
特許番号
US08304446B2

反応ノート

読み込み中…

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