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

HRID 1874729노트

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HRID 1874729 반응식
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

참가 물질

4

반응물 2

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

생성물 1

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

시약·촉매·용매 1

HCID 8028Tetrahydrofuran용매2회

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온도
0 °C

실험 절차

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)+.

후처리

  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

출처 및 근거

ORD 기록
ord-4c530350573f4f7cbf413d69f643aabe
출처 데이터셋
uspto-grants-2012_11
특허 번호
US08304446B2

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