Water → 2-(4-(6-fluoro-1H-indol-3-yl)-1H-pyrazol-1-yl)-N-methylethanamine

HRID 2274806Notes

Reaction equation

HRID 2274806 reaction equation
[H-].[H-].[H-].[H-].[Li+].[Al+3].[F:7][C:8]1[CH:16]=[C:15]2[C:11]([C:12]([C:26]3[CH:27]=[N:28][N:29]([CH2:31][CH2:32][NH:33][C:34](=O)OC(C)(C)C)[CH:30]=3)=[CH:13][N:14]2S(C2C=CC=CC=2)(=O)=O)=[CH:10][CH:9]=1.O.[OH-].[Na+]>C1COCC1>[F:7][C:8]1[CH:16]=[C:15]2[C:11]([C:12]([C:26]3[CH:27]=[N:28][N:29]([CH2:31][CH2:32][NH:33][CH3:34])[CH:30]=3)=[CH:13][NH:14]2)=[CH:10][CH:9]=1

Participants

6

Reactant 4

HCID 962Water2×HCID 14798Sodium HydroxideHCID 21226445Aluminium lithium hydrideHCID 118060702tert-butyl 2-(4-(6-fluoro-1-(phenylsulfonyl)-1H-indol-3-yl)-1H-pyrazol-1-yl)ethylcarbamate2×

Product 1

HCID 1180606692-(4-(6-fluoro-1H-indol-3-yl)-1H-pyrazol-1-yl)-N-methylethanamineYield 62%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

To a slurry of LiAlH4 (100 mg; 2.64 mmol) in THF (4 mL) was added a solution of tert-butyl 2-(4-(6-fluoro-1-(phenylsulfonyl)-1H-indol-3-yl)-1H-pyrazol-1-yl)ethylcarbamate (Intermediate 18; 300 mg; 0.62 mmol) in THF (6 mL) dropwise under argon. The reaction mixture was stirred at r.t. overnight and then at reflux for 4 hours. The reaction was added sequentially water (0.1 mL), 10% aqueous NaOH (0.2 mL), water (5 mL), filtered and washed with EtOAc. The filtrate was extracted with EtOAc (30 mL×2). The combined organic layers were dried over anhydrous Na2SO4, filtered, concentrated, and purified by a silica gel chromatography (DCM/MeOH=20/1) to afford the 94 mg (62%) of title compound as a yellow solid.

Workup

  1. temperatureat reflux for 4 hours
  2. filtrationfiltered
  3. washwashed with EtOAc
  4. extractionThe filtrate was extracted with EtOAc (30 mL×2)
  5. dry with materialThe combined organic layers were dried over anhydrous Na2SO4
  6. filtrationfiltered
  7. concentrationconcentrated
  8. custompurified by a silica gel chromatography (DCM/MeOH=20/1)

Sources & evidence

ORD record
ord-880e51c357e7482b8d110bfa221d87c2
Source dataset
uspto-grants-2015_09
Patent number
US09126984B2

Reaction notes

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