2-Bromo-1,5,6,7-tetrahydro-4H-indol-4-one → 2-(3-(tert-butylamino)-2-methylquinoxalin-5-yl)-6,7-dihydro-1H-indol-4(5H)-one

HRID 1056160Notes

Reaction equation

HRID 1056160 reaction equation
[C:1]([NH:5][C:6]1[C:15]([CH3:16])=[N:14][C:13]2[C:8](=[C:9](B3OC(C)(C)C(C)(C)O3)[CH:10]=[CH:11][CH:12]=2)[N:7]=1)([CH3:4])([CH3:3])[CH3:2].Br[C:27]1[NH:28][C:29]2[CH2:30][CH2:31][CH2:32][C:33](=[O:36])[C:34]=2[CH:35]=1>O1CCOCC1.O.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[C:1]([NH:5][C:6]1[C:15]([CH3:16])=[N:14][C:13]2[C:8]([N:7]=1)=[C:9]([C:27]1[NH:28][C:29]3[CH2:30][CH2:31][CH2:32][C:33](=[O:36])[C:34]=3[CH:35]=1)[CH:10]=[CH:11][CH:12]=2)([CH3:2])([CH3:3])[CH3:4]

Participants

6

Reactant 2

HCID 587922772-Bromo-1,5,6,7-tetrahydro-4H-indol-4-oneHCID 89783758N-(tert-butyl)-3-methyl-8-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)quinoxalin-2-amine

Product 1

HCID 717319182-(3-(tert-butylamino)-2-methylquinoxalin-5-yl)-6,7-dihydro-1H-indol-4(5H)-oneYield 77%

Reagents, catalysts & solvents 3

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 962WaterSolvent2×HCID 312751,4-DioxaneSolvent

Conditions

Temperature
105 °C

Procedure

A mixture of N-(tert-butyl)-3-methyl-8-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)quinoxalin-2-amine (174b) (222.6 mg, 0.652 mmol), 2-bromo-6,7-dihydro-1H-indol-4(5H)-one (303a; 209 mg, 0.978 mmol), K2PO4 (415 mg, 1.957 mmol), (Strem Chemicals, Inc., 31.1 mg, 0.065 mmol), and Pd2dba3 (Aldrich, 29.9 mg, 0.033 mmol) in a mixture of dioxane (4.5 mL) and water (0.900 mL) was heated under argon at 105° C. for 1 h. The reaction mixture was subsequently cooled to RT and diluted with water (30 mL). The resulting mixture was extracted with 5% MeOH/DCM (3×30 mL), and the combined extracts were dried over Na2SO4, filtered, and concentrated onto silica gel. Chromatographic purification (silica gel, 0-100% EtOAc/hexanes) furnished 2-(3-(tert-butylamino)-2-methylquinoxalin-5-yl)-6,7-dihydro-1H-indol-4(5H)-one (175 mg, 0.502 mmol, 77% yield) as a yellow solid: 1H NMR (400 MHz, CDCl3) δ ppm 12.52 (1H, br. s.), 7.96 (1H, dd, J=7.6, 1.0 Hz), 7.73 (1H, d, J=7.8 Hz), 7.40 (1H, t, J=7.8 Hz), 7.08 (1H, d, J=2.0 Hz), 4.89 (1H, s), 2.93 (2H, t, J=6.2 Hz), 2.60 (3H, s), 2.51-2.57 (2H, m), 2.23 (2H, quin, J=6.3 Hz), 1.68 (9H, s). m/z (ESI, +ve) 349.2 (M+H)+.

Workup

  1. temperatureThe reaction mixture was subsequently cooled to RT
  2. extractionThe resulting mixture was extracted with 5% MeOH/DCM (3×30 mL)
  3. dry with materialthe combined extracts were dried over Na2SO4
  4. filtrationfiltered
  5. concentrationconcentrated onto silica gel
  6. customChromatographic purification (silica gel, 0-100% EtOAc/hexanes)

Sources & evidence

ORD record
ord-fe09607228bf400e9d67bde659e4d1b3
Source dataset
uspto-grants-2016_07
Patent number
US09394297B2

Reaction notes

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