Sodium Hydroxide → 5-Chloro-N-[1-[(4-{[2-(dimethylamino)ethyl]oxy}phenyl)methyl]-4-(methyloxy)-1H-indazol-3-yl]-2-thiophenesulfonamide

HRID 1874725ノート

反応式

HRID 1874725 の反応式
[Cl:1][C:2]1[S:6][C:5]([S:7]([N:10](S(C2SC(Cl)=CC=2)(=O)=O)[C:11]2[C:19]3[C:14](=[CH:15][CH:16]=[CH:17][C:18]=3[O:20][CH3:21])[N:13]([CH2:22][C:23]3[CH:28]=[CH:27][C:26]([O:29][CH2:30][CH2:31][N:32]([CH3:34])[CH3:33])=[CH:25][CH:24]=3)[N:12]=2)(=[O:9])=[O:8])=[CH:4][CH:3]=1.[OH-].[Na+]>CO>[Cl:1][C:2]1[S:6][C:5]([S:7]([NH:10][C:11]2[C:19]3[C:14](=[CH:15][CH:16]=[CH:17][C:18]=3[O:20][CH3:21])[N:13]([CH2:22][C:23]3[CH:24]=[CH:25][C:26]([O:29][CH2:30][CH2:31][N:32]([CH3:33])[CH3:34])=[CH:27][CH:28]=3)[N:12]=2)(=[O:8])=[O:9])=[CH:4][CH:3]=1

参加物

4

反応物 2

HCID 14798Sodium HydroxideHCID 580545145-Chloro-N-[(5-chloro-2-thienyl)sulfonyl]-N-[1-[(4-{[2-(dimethylamino)ethyl]oxy}phenyl)methyl]-4-(methyloxy)-1H-indazol-3-yl]-2-thiophenesulfonamide

生成物 1

HCID 594560635-Chloro-N-[1-[(4-{[2-(dimethylamino)ethyl]oxy}phenyl)methyl]-4-(methyloxy)-1H-indazol-3-yl]-2-thiophenesulfonamide収率 64%

試薬・触媒・溶媒 1

HCID 887Methanol溶媒

反応条件

温度
70 °C

実験手順

A solution of 5-chloro-N-[(5-chloro-2-thienyl)sulfonyl]-N-[1-[(4-{[2-(dimethylamino)ethyl]oxy}phenyl)methyl]-4-(methyloxy)-1H-indazol-3-yl]-2-thiophenesulfonamide (for a preparation see Intermediate 18) (91 mg, 0.13 mmol) in MeOH (5 mL) was treated with a 2M aq. NaOH solution (1 mL) and the mixture was heated to 70° C. for 2 h, and then allowed to stand at RT over the weekend. The solvents evaporated by this time and the white solid residue was diluted with water and 2M HCl solution (1 mL) and extracted with ethyl acetate. The organic solution was washed with brine, dried (MgSO4) and evaporated to dryness (72 mg). The residue was dissolved in 1:1 MeOH:DMSO (1 mL) and purified by MDAP on Xbridge column using acetonitrile-water with an ammonium carbonate modifier. The solvent was evaporated in vacuo to give the title compound (43 mg, 64%) as a colourless gum. LCMS (System C) RT=2.20 min, ES+ve m/z 521/523 (M+H)+.

後処理

  1. customto stand at RT over the weekend
  2. customThe solvents evaporated by this time
  3. additionthe white solid residue was diluted with water and 2M HCl solution (1 mL)
  4. extractionextracted with ethyl acetate
  5. washThe organic solution was washed with brine
  6. dry with materialdried (MgSO4)
  7. customevaporated to dryness (72 mg)
  8. dissolutionThe residue was dissolved in 1:1 MeOH
  9. customDMSO (1 mL) and purified by MDAP on Xbridge column
  10. customThe solvent was evaporated in vacuo

出典と根拠

ORDレコード
ord-67a4934480c24d179d7fa1dae67ffb10
出典データセット
uspto-grants-2012_11
特許番号
US08304446B2

反応ノート

読み込み中…