Sodium hydride → 1-(1-Amino-4-bromo-isoquinolin-6-yl)-3,6,6-trimethyl-1,5,6,7-tetrahydro-indol-4-one

HRID 2244069Notes

Reaction equation

HRID 2244069 reaction equation
[NH2:1][C:2]1[C:11]2[C:6](=[CH:7][C:8](F)=[CH:9][CH:10]=2)[C:5]([Br:13])=[CH:4][N:3]=1.[CH3:14][C:15]1[C:23]2[C:22](=[O:24])[CH2:21][C:20]([CH3:26])([CH3:25])[CH2:19][C:18]=2[NH:17][CH:16]=1.[H-].[Na+].[NH4+].[Cl-]>CN(C=O)C>[NH2:1][C:2]1[C:11]2[C:6](=[CH:7][C:8]([N:17]3[C:18]4[CH2:19][C:20]([CH3:25])([CH3:26])[CH2:21][C:22](=[O:24])[C:23]=4[C:15]([CH3:14])=[CH:16]3)=[CH:9][CH:10]=2)[C:5]([Br:13])=[CH:4][N:3]=1

Participants

6

Reactant 4

HCID 24758Sodium hydrideHCID 25517Ammonium ChlorideHCID 248207983,6,6-trimethyl-6,7-dihydro-1H-indol-4(5H)-oneHCID 250594381-Amino-4-bromo-6-fluoro-isoquinoline

Product 1

HCID 250609791-(1-Amino-4-bromo-isoquinolin-6-yl)-3,6,6-trimethyl-1,5,6,7-tetrahydro-indol-4-oneYield 25%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of 1-amino-4-bromo-6-fluoro-isoquinoline (0.029 g, 0.12 mmol) in DMF (1 mL) are added 3,6,6-Trimethyl-1,5,6,7-tetrahydro-indol-4-one (0.042 g, 0.24 mmol) and NaH (0.01 g, 0.24 mmol). The reaction mixture is microwaved at 120° C. for 40 min, cooled to RT, and treated with NH4Cl (satd. aq, 2 mL). The aqueous phase is extracted with EtOAc (2×). The combined organic layers are washed with brine, and dried over MgSO4. The solvent is evaporated and the residue is dried under vacuum. Purification of the crude material using a Biotage column (0-10% MeOH/CH2Cl2) affords 0.0118 g (25%) of 1-(1-Amino-4-bromo-isoquinolin-6-yl)-3,6,6-trimethyl-1,5,6,7-tetrahydro-indol-4-one. LC/MS m/z=399 [M+H]+.

Workup

  1. customThe reaction mixture is microwaved at 120° C. for 40 min
  2. extractionThe aqueous phase is extracted with EtOAc (2×)
  3. washThe combined organic layers are washed with brine
  4. dry with materialdried over MgSO4
  5. customThe solvent is evaporated
  6. customthe residue is dried under vacuum
  7. customPurification of the crude material

Sources & evidence

ORD record
ord-a2f1fef9ac4e42659afc6f04e0e6cd49
Source dataset
uspto-grants-2010_03
Patent number
US07678803B2

Reaction notes

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