Potassium Carbonate → 2-(3-(tert-butylamino)-2-ethynylquinoxalin-5-yl)-6,7-dihydro-1H-pyrrolo[3,2-c]pyridin-4(5H)-one

HRID 1056170Notes

Reaction equation

COP([C:7](=[N+:11]=[N-])[C:8](=O)[CH3:9])(=O)OC.[C:13]([NH:17][C:18]1C(C=O)=N[C:21]2[C:26]([N:27]=1)=[C:25]([C:28]1[NH:36][C:35]3[CH2:34][CH2:33][NH:32][C:31](=[O:37])[C:30]=3[CH:29]=1)[CH:24]=[CH:23][CH:22]=2)([CH3:16])([CH3:15])[CH3:14].C([O-])([O-])=O.[K+].[K+].CO.C(Cl)Cl>CO.CCOCC>[C:13]([NH:17][C:18]1[C:7]([C:8]#[CH:9])=[N:11][C:21]2[C:26]([N:27]=1)=[C:25]([C:28]1[NH:36][C:35]3[CH2:34][CH2:33][NH:32][C:31](=[O:37])[C:30]=3[CH:29]=1)[CH:24]=[CH:23][CH:22]=2)([CH3:16])([CH3:14])[CH3:15]

Participants

Conditions

Temperature: 23 °C

Procedure

Dimethyl(1-diazo-2-oxopropyl)phosphonate (Anichem, Inc., North Brunswick, N.J.; 8.63 μl, 0.06 mmol) was added to a suspension of 3-(tert-butylamino)-5-(4-oxo-4,5,6,7-tetrahydro-1H-pyrrolo[3,2-c]pyridin-2-yl)quinoxaline-2-carbaldehyde (307b) (19.0 mg, 0.05 mmol) and K2CO3 (28.9 mg, 0.21 mmol) in MeOH (1.0 mL) and the resulting mixture was stirred at 23° C. for 16 h. Additional dimethyl(1-diazo-2-oxopropyl)phosphonate (20 μl, 0.13 mmol) was added, and the resulting mixture was stirred at 23° C. for 17 h. The reaction mixture was subsequently concentrated onto silica gel and chromatographically purified (silica gel, 0-100% EtOAc/hexanes, then 0-10% MeOH/DCM) to provide 2-(3-(tert-butylamino)-2-ethynylquinoxalin-5-yl)-6,7-dihydro-1H-pyrrolo[3,2-c]pyridin-4(5H)-one (2.8 mg, 7.79 μmol, 15% yield) as a yellow solid (following trituration with Et2O (0.5 mL)): 1H NMR (400 MHz, CDCl3) δ ppm 12.39 (1H, br. s.), 8.14 (1H, d, J=7.4 Hz), 8.10 (1H, d, J=8.0 Hz), 8.04 (1H, d, J=3.9 Hz), 7.72 (1H, t, J=7.8 Hz), 6.82 (1H, d, J=3.7 Hz), 5.49 (1H, br. s.), 3.81-3.86 (1H, m), 3.68-3.75 (2H, m), 3.06 (2H, t, J=6.9 Hz), 1.96 (9H, s). m/z (ESI, +ve) 360.2 (M+H)+.

Workup

stirringthe resulting mixture was stirred at 23° C. for 17 h
concentrationThe reaction mixture was subsequently concentrated onto silica gel
customchromatographically purified (silica gel, 0-100% EtOAc/hexanes

Sources & evidence

ORD record: ord-2d9914df86564764b75d75ce33448e62
Source dataset: uspto-grants-2016_07
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09394297B2

Reaction notes

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