Diisopropylethylamine → 8-(2,6-dichloro-3,5-dimethoxy-phenyl)-quinoxaline-5-carboxylic acid [1-(2-trimethylsilanyl-ethoxymethyl)-1H-imidazol-2-yl]-amide

HRID 1189745Notes

Reaction equation

HRID 1189745 reaction equation
[Cl:1][C:2]1[C:7]([O:8][CH3:9])=[CH:6][C:5]([O:10][CH3:11])=[C:4]([Cl:12])[C:3]=1[C:13]1[C:22]2[N:21]=[CH:20][CH:19]=[N:18][C:17]=2[C:16]([C:23](O)=[O:24])=[CH:15][CH:14]=1.[CH3:26][Si:27]([CH3:39])([CH3:38])[CH2:28][CH2:29][O:30][CH2:31][N:32]1[CH:36]=[CH:35][N:34]=[C:33]1[NH2:37].CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.[B-](F)(F)(F)F.CCN(C(C)C)C(C)C>CN(C=O)C.CCOC(C)=O.O>[CH3:26][Si:27]([CH3:39])([CH3:38])[CH2:28][CH2:29][O:30][CH2:31][N:32]1[CH:36]=[CH:35][N:34]=[C:33]1[NH:37][C:23]([C:16]1[C:17]2[N:18]=[CH:19][CH:20]=[N:21][C:22]=2[C:13]([C:3]2[C:4]([Cl:12])=[C:5]([O:10][CH3:11])[CH:6]=[C:7]([O:8][CH3:9])[C:2]=2[Cl:1])=[CH:14][CH:15]=1)=[O:24]

Participants

8

Reactant 4

HCID 81531DiisopropylethylamineHCID 2733207O-(Benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborateHCID 592928388-(2,6-Dichloro-3,5-dimethoxy-phenyl)quinoxaline-5-carboxylic acidHCID 669145481-(2-trimethylsilanyl-ethoxymethyl)-1H-imidazol-2-ylamine

Product 1

HCID 866411408-(2,6-dichloro-3,5-dimethoxy-phenyl)-quinoxaline-5-carboxylic acid [1-(2-trimethylsilanyl-ethoxymethyl)-1H-imidazol-2-yl]-amideYield 85.1%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

A mixture of 8-(2,6-dichloro-3,5-dimethoxy-phenyl)quinoxaline-5-carboxylic acid (Step 1.1) (0.400 g, 1.06 mmol), 1-(2-trimethylsilanyl-ethoxymethyl)-1H-imidazol-2-ylamine (Step 14.2) (0.270 g, 1.27 mmol, 1.2 equiv), TBTU (408 mg, 1.27 mmol, 1.2 equiv), DIEA (0.74 mL, 4.23 mmol, 4.0 equiv) in DMF (5 mL) was stirred for 2 h at rt, diluted with EtOAc and H2O, and extracted with EtOAc.washed with a saturated aqueous solution of NaHCO3, H2O, and brine. The organic phase was washed with H2O and brine, dried (Na2SO4), filtered and concentrated. The residue was purified by silica gel column chromatography (DCM/MeOH, 95:5) to afford 0.518 g of the title compound as a yellow foam: ES-MS: 573.8/575.8 [M+H]+; tR=5.03 min (System 1); Rf=0.19 (DCM2/MeOH, 95:5).

Workup

  1. extractionextracted with EtOAc
  2. washwashed with a saturated aqueous solution of NaHCO3, H2O, and brine
  3. washThe organic phase was washed with H2O and brine
  4. dry with materialdried (Na2SO4)
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customThe residue was purified by silica gel column chromatography (DCM/MeOH, 95:5)

Sources & evidence

ORD record
ord-f0d7cfafb2f945efaa029f981b7a7d41
Source dataset
uspto-grants-2014_03
Patent number
US08674099B2

Reaction notes

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