Hydroxyamine hydrochloride → 2-[3-(tert-butylamino)-2-[(E)-hydroxyiminomethyl]quinoxalin-5-yl]-1,5,6,7-tetrahydropyrrolo[3,2-c]pyridin-4-one

HRID 1056171Notes

Reaction equation

HRID 1056171 reaction equation
[C:1]([NH:5][C:6]1[C:7]([CH:26]=O)=[N:8][C:9]2[C:14]([N:15]=1)=[C:13]([C:16]1[NH:24][C:23]3[CH2:22][CH2:21][NH:20][C:19](=[O:25])[C:18]=3[CH:17]=1)[CH:12]=[CH:11][CH:10]=2)([CH3:4])([CH3:3])[CH3:2].Cl.[NH2:29][OH:30].CO.C(Cl)Cl>CO.C([O-])(O)=O.[Na+]>[C:1]([NH:5][C:6]1[C:7](/[CH:26]=[N:29]/[OH:30])=[N:8][C:9]2[C:14]([N:15]=1)=[C:13]([C:16]1[NH:24][C:23]3[CH2:22][CH2:21][NH:20][C:19](=[O:25])[C:18]=3[CH:17]=1)[CH:12]=[CH:11][CH:10]=2)([CH3:3])([CH3:4])[CH3:2]

Participants

6

Reactant 3

HCID 443297Hydroxyamine hydrochlorideHCID 21226129Dichloromethane methanolHCID 897835263-(tert-butylamino)-5-(4-oxo-4,5,6,7-tetrahydro-1H-pyrrolo[3,2-c]pyridin-2-yl)quinoxaline-2-carbaldehyde

Product 1

HCID 1362179662-[3-(tert-butylamino)-2-[(E)-hydroxyiminomethyl]quinoxalin-5-yl]-1,5,6,7-tetrahydropyrrolo[3,2-c]pyridin-4-oneYield 68.3%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 516892Sodium BicarbonateSolvent

Procedure

A solution of 3-(tert-butylamino)-5-(4-oxo-4,5,6,7-tetrahydro-1H-pyrrolo[3,2-c]pyridin-2-yl)quinoxaline-2-carbaldehyde (307b) (44.0 mg, 0.12 mmol), hydroxylamine hydrochloride (11.7 mg, 0.17 mmol), and TEA (0.024 mL, 0.17 mmol) in MeOH (5.0 mL) was stirred at 60° C. for 1.5 h. The reaction mixture was subsequently cooled to RT, diluted with saturated aq. NaHCO3 (20 mL), and extracted with 5% MeOH/DCM (2×30 mL). The combined extracts were sequentially washed with water (30 mL) and brine (20 mL), dried over Na2SO4, filtered, and concentrated onto silica gel. Chromatographic purification (silica gel, 0-100% EtOAc/hexanes, then 0-10% MeOH/DCM) furnished (E)-3-(tert-butylamino)-5-(4-oxo-4,5,6,7-tetrahydro-1H-pyrrolo[3,2-c]pyridin-2-yl)quinoxaline-2-carbaldehyde oxime (31.0 mg, 0.082 mmol, 68% yield) as an orange solid: 1H NMR (400 MHz, DMSO-d6) δ ppm 12.34 (1H, br. s.), 11.86 (1H, br. s.), 8.34 (1H, s), 8.31 (1H, s), 7.91 (1H, dd, J=7.3, 1.1 Hz), 7.67 (1H, dd, J=8.0, 1.0 Hz), 7.40 (1H, t, J=7.8 Hz), 7.09 (1H, d, J=2.2 Hz), 6.95 (1H, br. s.), 3.43 (2H, td, J=6.8, 2.2 Hz), 2.86 (2H, t, J=6.8 Hz), 1.57 (9H, s). m/z (ESI, +ve) 379.1 (M+H)+.

Workup

  1. extractionextracted with 5% MeOH/DCM (2×30 mL)
  2. washThe combined extracts were sequentially washed with water (30 mL) and brine (20 mL)
  3. dry with materialdried over Na2SO4
  4. filtrationfiltered
  5. concentrationconcentrated onto silica gel
  6. customChromatographic purification (silica gel, 0-100% EtOAc/hexanes

Sources & evidence

ORD record
ord-ff3d15317378462a90aa7e4d5a57a77d
Source dataset
uspto-grants-2016_07
Patent number
US09394297B2

Reaction notes

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