Sodium Carbonate → 2-(2-methyl-3-(o-tolyl)quinoxalin-5-yl)-6,7-dihydro-1H-pyrrolo[3,2-c]pyridin-4(5H)-one

HRID 1056306Notes

Reaction equation

HRID 1056306 reaction equation
Cl[C:2]1[C:3]([CH3:22])=[N:4][C:5]2[C:10]([N:11]=1)=[C:9]([C:12]1[NH:20][C:19]3[CH2:18][CH2:17][NH:16][C:15](=[O:21])[C:14]=3[CH:13]=1)[CH:8]=[CH:7][CH:6]=2.[C:23]1([CH3:32])[CH:28]=[CH:27][CH:26]=[CH:25][C:24]=1B(O)O.C([O-])([O-])=O.[Na+].[Na+].CO.C(Cl)Cl>O1CCOCC1.O.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[CH3:22][C:3]1[C:2]([C:24]2[CH:25]=[CH:26][CH:27]=[CH:28][C:23]=2[CH3:32])=[N:11][C:10]2[C:5](=[CH:6][CH:7]=[CH:8][C:9]=2[C:12]2[NH:20][C:19]3[CH2:18][CH2:17][NH:16][C:15](=[O:21])[C:14]=3[CH:13]=2)[N:4]=1

Participants

8

Reactant 4

HCID 10340Sodium CarbonateHCID 27332672-Methylphenyl boronic acidHCID 21226129Dichloromethane methanolHCID 897835202-(3-chloro-2-methylquinoxalin-5-yl)-6,7-dihydro-1H-pyrrolo[3,2-c]pyridin-4(5H)-one

Product 1

HCID 897834382-(2-methyl-3-(o-tolyl)quinoxalin-5-yl)-6,7-dihydro-1H-pyrrolo[3,2-c]pyridin-4(5H)-oneYield 92%

Reagents, catalysts & solvents 3

HCID 178418397HCID 178418397, compoundCatalystHCID 962WaterSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
100 °C

Procedure

A solution of 2-(3-chloro-2-methylquinoxalin-5-yl)-6,7-dihydro-1H-pyrrolo[3,2-c]pyridin-4(5H)-one (Example 425; 50.3 mg, 0.161 mmol), o-tolylboronic acid (Aldrich; 32.8 mg, 0.241 mmol), Na2CO3 (51.1 mg, 0.482 mmol), and Pd(PPh3)4 (Strem Chemicals, Inc.; 9.29 mg, 8.04 μmol) in a mixture of 1,4-dioxane (1.5 mL) and water (0.500 mL) was stirred under argon at 100° C. for 45 min. The mixture was concentrated onto silica gel and chromatographically purified (silica gel, 50-100% EtOAc/hexanes, then 0-10% MeOH/DCM) to provide 2-(2-methyl-3-(o-tolyl)quinoxalin-5-yl)-6,7-dihydro-1H-pyrrolo[3,2-c]pyridin-4(5H)-one (54.6 mg, 0.148 mmol, 92% yield) as a brown solid. 1H NMR (400 MHz, CDCl3) δ ppm 12.12 (1H, br. s.), 8.11 (1H, dd, J=7.4, 0.8 Hz), 7.90 (1H, dd, J=8.3, 0.9 Hz), 7.77 (1H, t, J=8.0 Hz), 7.31-7.49 (4H, m), 7.25 (1H, d, J=2.2 Hz), 5.38 (1H, br. s.), 3.58 (2H, td, J=6.7, 2.1 Hz), 2.85 (2H, t, J=6.8 Hz), 2.59 (3H, s), 2.21 (3H, s). m/z (ESI, +ve) 368.9 (M+H)+.

Workup

  1. concentrationThe mixture was concentrated onto silica gel
  2. customchromatographically purified (silica gel, 50-100% EtOAc/hexanes

Sources & evidence

ORD record
ord-2c65c86157d04874a22c091f72d8577e
Source dataset
uspto-grants-2016_07
Patent number
US09394297B2

Reaction notes

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