Aluminium lithium hydride → N-{[3-({4-(Methyloxy)-3-[(2-thienylsulfonyl)amino]-1H-indazol-1-yl}methyl)phenyl]methyl}acetamide

HRID 1808623ノート

反応式

HRID 1808623 の反応式
Cl[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]=[C:25]([CH2:29][NH:30][C:31](=[O:33])[CH3:32])[CH:26]=[CH:27][CH:28]=3)[N:12]=2)(=[O:9])=[O:8])=[CH:4][CH:3]=1.[H-].[Al+3].[Li+].[H-].[H-].[H-]>C1COCC1>[CH3:21][O:20][C:18]1[CH:17]=[CH:16][CH:15]=[C:14]2[C:19]=1[C:11]([NH:10][S:7]([C:5]1[S:6][CH:2]=[CH:3][CH:4]=1)(=[O:8])=[O:9])=[N:12][N:13]2[CH2:22][C:23]1[CH:24]=[C:25]([CH2:29][NH:30][C:31](=[O:33])[CH3:32])[CH:26]=[CH:27][CH:28]=1

参加物

4

反応物 2

HCID 21226445Aluminium lithium hydrideHCID 59456102N-[(3-{[3-{[(5-Chloro-2-thienyl)sulfonyl]amino}-4-(methyloxy)-1H-indazol-1-yl]methyl}phenyl)methyl]acetamide

生成物 1

HCID 59456004N-{[3-({4-(Methyloxy)-3-[(2-thienylsulfonyl)amino]-1H-indazol-1-yl}methyl)phenyl]methyl}acetamide収率 64%

試薬・触媒・溶媒 1

HCID 8028Tetrahydrofuran溶媒2 回

反応条件

温度
0 °C

実験手順

To a cooled (ice/water bath) solution of N-[(3-{[3-{[(5-chloro-2-thienyl)sulfonyl]amino}-4-(methyloxy)-1H-indazol-1-yl]methyl}phenyl)methyl]acetamide (for a preparation see Example 1) (30 mg, 0.06 mmol) in THF (1 mL) was added dropwise 2M lithium aluminium hydride in THF (0.074 mL, 0.149 mmol), and the suspension was stirred 10 min at 0° C. and then at room temperature for one hour. Reaction was quenched with 4 drops of water and then with aqueous solution of sodium hydroxide (2M, 0.5 mL). After stirring for 30 min, solid was removed and washed with THF (10 mL). The filtrate was concentrated under reduced pressure and the residue was dissolved in 1:1 MeOH-DMSO (1 mL) and purified by Mass Directed AutoPrep on Sunfire C18 column using Acetonitrile Water with a TFA modifier (Method B). The solvent from appropriate fractions was evaporated under a stream of nitrogen in a Radleys blowdown apparatus to give the title compound (18 mg, 64%). LCMS (System A) RT=0.89 min, ES+ve m/z 471 (M+H)+.

後処理

  1. waitat room temperature for one hour
  2. customReaction
  3. customwas quenched with 4 drops of water
  4. stirringAfter stirring for 30 min
  5. customsolid was removed
  6. washwashed with THF (10 mL)
  7. concentrationThe filtrate was concentrated under reduced pressure
  8. dissolutionthe residue was dissolved in 1:1 MeOH-DMSO (1 mL)
  9. custompurified by Mass Directed AutoPrep on Sunfire C18 column
  10. customThe solvent from appropriate fractions was evaporated under a stream of nitrogen in a Radleys blowdown apparatus

出典と根拠

ORDレコード
ord-326972fbb3504f288f0818d3dfe0f021
出典データセット
uspto-grants-2013_01
特許番号
US08357716B2

反応ノート

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