Water → Tert-butyl (2-((8-(2-bromoacetyl)-3-methylquinoxalin-2-yl)amino)-2-methylpropyl)carbamate

HRID 1056215Notes

Reaction equation

HRID 1056215 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]([CH3:33])([CH3:32])[CH2:23][NH:24][C:25](=[O:31])[O:26][C:27]([CH3:30])([CH3:29])[CH3:28])[C:17]([CH3:34])=[N:16]2)=[CH2:10])(C(C)(C)C)(C)C.[Br:35]N1C(=O)CCC1=O.O>C1COCC1.C(Cl)Cl>[Br:35][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]([CH3:33])([CH3:32])[CH2:23][NH:24][C:25](=[O:31])[O:26][C:27]([CH3:30])([CH3:29])[CH3:28])[C:17]([CH3:34])=[N:16]2)=[O:10]

Participants

6

Reactant 3

HCID 962WaterHCID 67184N-bromobutanimideHCID 89793770Tert-butyl (2-((8-(1-((tert-butyldimethylsilyl)oxy)vinyl)-3-methylquinoxalin-2-yl)amino)-2-methylpropyl)carbamate

Product 1

HCID 89793771Tert-butyl (2-((8-(2-bromoacetyl)-3-methylquinoxalin-2-yl)amino)-2-methylpropyl)carbamateYield 52%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 8028TetrahydrofuranSolvent

Procedure

A solution of tert-butyl (2-((8-(1-((tert-butyldimethylsilyl)oxy)vinyl)-3-methylquinoxalin-2-yl)amino)-2-methylpropyl)carbamate (339b), 1-bromopyrrolidine-2,5-dione (0.41 g, 2.30 mmol), and water (0.60 mL, 33.5 mmol) in THF (21 mL) was stirred at 0° C. and warmed to RT and stir for 30 min when product was observed via lcms. The reaction mixture was diluted with DCM (100 mL), added to a separatory funnel, and washed with saturated aq. NaHCO3 (100 mL); 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 10-40% EtOAc in hexanes to give tert-butyl (2-((8-(2-bromoacetyl)-3-methylquinoxalin-2-yl)amino)-2-methylpropyl)carbamate (339c) (0.49 g, 1.08 mmol, 52% yield) as a yellow amorphous solid. 1H NMR (400 MHz, CDCl3) δ ppm 1.48 (s, 9H) 1.57 (s, 6H) 2.55 (s, 3H) 3.32 (d, J=6.85 Hz, 2H) 5.00 (s, 2H) 5.11 (dd, J=7.63, 5.09 Hz, 1H) 6.73 (s, 1H) 7.36 (t, J=7.73 Hz, 1H) 7.85 (d, J=7.24 Hz, 1H) 7.93 (d, J=8.02 Hz, 1H). MS (ESI, pos. ion) m/z: 451.2/453.2 (M+1).

Workup

  1. additionadded to a separatory funnel
  2. washwashed with saturated aq. NaHCO3 (100 mL)
  3. customthe organic layer was separated
  4. dry with materialdried over Na2SO4
  5. concentrationconcentrated
  6. customwas purified

Sources & evidence

ORD record
ord-024c21eb4ec54c099091b531bd85221a
Source dataset
uspto-grants-2016_07
Patent number
US09394297B2

Reaction notes

Loading…