Water → 2-Bromo-1-(2-methyl-3-((2-methyl-4-(methylsulfonyl)butan-2-yl)amino)quinoxalin-5-yl)ethanone
Reaction equation
[Si]([O:8][C:9]([C:11]1[CH:12]=[CH:13][CH:14]=[C:15]2[C:20]=1[N:19]=[C:18]([NH:21][C:22]([CH3:30])([CH2:24][CH2:25][S:26]([CH3:29])(=[O:28])=[O:27])[CH3:23])[C:17]([CH3:31])=[N:16]2)=[CH2:10])(C(C)(C)C)(C)C.[Br:32]N1C(=O)CCC1=O.O>C1COCC1.C(Cl)Cl>[Br:32][CH2:8][C:9]([C:11]1[CH:12]=[CH:13][CH:14]=[C:15]2[C:20]=1[N:19]=[C:18]([NH:21][C:22]([CH3:30])([CH2:24][CH2:25][S:26]([CH3:29])(=[O:28])=[O:27])[CH3:23])[C:17]([CH3:31])=[N:16]2)=[O:10]Participants
Reactant 3
Product 1
Reagents, catalysts & solvents 2
Procedure
A solution of 8-(1-((tert-butyldimethylsilyl)oxy)vinyl)-3-methyl-N-(2-methyl-4-(methylsulfonyl)butan-2-yl)quinoxalin-2-amine (338d), 1-bromopyrrolidine-2,5-dione (0.26 g, 1.46 mmol), and water (0.42 mL, 23.49 mmol) in THF (14.68 mL) was stirred at 0° C. for 15 min before it was warmed to RT and stir for 2 h when product was observed via lcms. The reaction mixture was diluted with DCM (150 mL), added to a separatory funnel, and washed with saturated aq. NaHCO3 (75 mL) before the organic layer was separated, dried over Na2SO4, and concentrated. The crude product was adsorbed onto silica and was purified via automated flash chromatography (silica gel) with 100% DCM followed by 3% 2 M NH3 in MeOH/DCM to give 2-bromo-1-(2-methyl-3-((2-methyl-4-(methylsulfonyl)butan-2-yl)amino)quinoxalin-5-yl)ethanone (338e, 306 mg, 0.71 mmol, 49% yield) as a red oil. MS (ESI, pos. ion) m/z: 428.2/430.2 (M+1).
Workup
- additionadded to a separatory funnel
- washwashed with saturated aq. NaHCO3 (75 mL) before the organic layer
- customwas separated
- dry with materialdried over Na2SO4
- concentrationconcentrated
- customwas purified
Sources & evidence
- ORD record
- ord-69c0d83355a74b92a5b086858cba0616
- Source dataset
- uspto-grants-2016_07
- Patent number
- US09394297B2
Reaction notes
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