Trifluoroacetic acid → 2-(2-methyl-3-((2,2,2-trifluoroethyl)amino)quinoxalin-5-yl)-6,7-dihydro-1H-pyrrolo[3,2-c]pyridin-4(5H)-one

HRID 1056207Notes

Reaction equation

HRID 1056207 reaction equation
Br[CH2:2][C:3]([C:5]1[CH:14]=[CH:13][CH:12]=[C:11]2[C:6]=1[N:7]=[C:8]([NH:16][CH2:17][C:18]([F:21])([F:20])[F:19])[C:9]([CH3:15])=[N:10]2)=O.[NH:22]1[CH2:27][CH2:26][C:25](=O)[CH2:24][C:23]1=[O:29].CC#[N:32].O.C(O)(C(F)(F)F)=O>CCO.CS(C)=O>[CH3:15][C:9]1[C:8]([NH:16][CH2:17][C:18]([F:21])([F:20])[F:19])=[N:7][C:6]2[C:11](=[CH:12][CH:13]=[CH:14][C:5]=2[C:3]2[NH:32][C:25]3[CH2:26][CH2:27][NH:22][C:23](=[O:29])[C:24]=3[CH:2]=2)[N:10]=1

Participants

7

Reactant 4

HCID 6422Trifluoroacetic acidHCID 108878632,4-PiperidinedioneHCID 18373917Acetonitrile--water (1/1)HCID 897820082-Bromo-1-(2-methyl-3-((2,2,2-trifluoroethyl)amino)quinoxalin-5-yl)ethanone

Product 1

HCID 717303682-(2-methyl-3-((2,2,2-trifluoroethyl)amino)quinoxalin-5-yl)-6,7-dihydro-1H-pyrrolo[3,2-c]pyridin-4(5H)-oneYield 6%

Reagents, catalysts & solvents 2

HCID 679Dimethyl SulfoxideSolventHCID 702EthanolSolvent

Procedure

A solution of 2-bromo-1-(2-methyl-3-((2,2,2-trifluoroethyl)amino)quinoxalin-5-yl)ethanone (616) (40 mg, 0.11 mmol), piperidine-2,4-dione (Inogent, Hyderabad, India) (24.99 mg, 0.22 mmol), and NH4OAc (42.6 mg, 0.55 mmol) in EtOH (1.1 mL) was stirred at 40° C. for 2.5 d. The crude product was adsorbed onto silica and was purified via automated flash chromatography (silica gel) with 100% DCM to 4% 2 M NH3 in MeOH/DCM to give impure product. The crude product was dissolved in DMSO (˜20 mg/mL) and injected (1×1.0 mL) onto the Shimadzu preparatory LC (Phenomenex Gemini C18, 10 μm, 150×30 mm; 10-100% MeCN/water with 0.1% TFA); the pure fraction was concentrated via rotary evaporation to give 2-(2-methyl-3-((2,2,2-trifluoroethyl)amino)quinoxalin-5-yl)-6,7-dihydro-1H-pyrrolo[3,2-c]pyridin-4(5H)-one (336) (4 mg, 6% yield) as a brick red solid. 1H NMR (400 MHz, MeOH) δ ppm 2.66 (s, 3H) 2.99 (t, J=7.04 Hz, 2H) 3.65 (t, J=7.24 Hz, 2H) 4.38 (q, J=9.52 Hz, 2H) 7.09 (s, 1H) 7.48 (t, J=7.82 Hz, 1H) 7.70 (d, J=8.02 Hz, 1H) 7.98 (d, J=7.24 Hz, 1H) 11.98 (br. s., 1H). 19F NMR (377 MHz, MeOH) δ ppm −77.59 (br. s., 6F) −72.18 (s, 3F). MS (ESI, pos. ion) m/z: 376.1 (M+1).

Workup

  1. customwas purified
  2. customto give impure product
  3. concentrationthe pure fraction was concentrated via rotary evaporation

Sources & evidence

ORD record
ord-aadb219f43a44d0385ae25af32336c46
Source dataset
uspto-grants-2016_07
Patent number
US09394297B2

Reaction notes

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