Cesium fluoride → 2-(2-methyl-3-(3-methylpyridin-2-yl)quinoxalin-5-yl)-6,7-dihydro-1H-pyrrolo[3,2-c]pyridin-4(5H)-one

HRID 1056310Notes

Reaction equation

HRID 1056310 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.[CH3:23][C:24]1[C:25]([Sn](CCCC)(CCCC)CCCC)=[N:26][CH:27]=[CH:28][CH:29]=1.[F-].[Cs+].CO.C(Cl)Cl>CN(C=O)C.[Cu]I.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:25]2[C:24]([CH3:23])=[CH:29][CH:28]=[CH:27][N:26]=2)=[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 25953Cesium fluorideHCID 164270983-Methyl-2-(tributylstannyl)pyridineHCID 21226129Dichloromethane methanolHCID 89783520HCID 89783520, compound

Product 1

HCID 897938492-(2-methyl-3-(3-methylpyridin-2-yl)quinoxalin-5-yl)-6,7-dihydro-1H-pyrrolo[3,2-c]pyridin-4(5H)-oneYield 42%

Reagents, catalysts & solvents 3

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 178418397HCID 178418397, compoundCatalystHCID 6228DimethylformamideSolvent

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; 33.7 mg, 0.108 mmol), 3-methyl-2-(tributylstannyl)pyridine (Indofine Chemical Company, Inc., Hillsborough, N.J.; 0.040 mL, 0.119 mmol), CuI (2.052 mg, 10.78 μmol), cesium fluoride (32.7 mg, 0.216 mmol), and Pd(PPh3)4 (Strem Chemicals, Inc.; 6.23 mg, 5.39 μmol) in DMF (2.0 mL) was stirred under argon in a microwave process vial at 140° C. for 30 min. The reaction mixture was then concentrated onto silica gel and chromatographically purified (silica gel, 50-100% EtOAc/hexanes, then 0-10% MeOH/DCM) to provide 2-(2-methyl-3-(3-methylpyridin-2-yl)quinoxalin-5-yl)-6,7-dihydro-1H-pyrrolo[3,2-c]pyridin-4(5H)-one (16.8 mg, 0.045 mmol, 42% yield) as a yellow-orange solid. 1H NMR (400 MHz, CDCl3) δ ppm 11.91 (1H, br. s.), 8.65 (1H, dd, J=4.5, 0.8 Hz), 8.10 (1H, dd, J=7.4, 1.2 Hz), 7.91 (1H, dd, J=8.2, 1.2 Hz), 7.74-7.82 (2H, m), 7.42 (1H, dd, J=7.8, 4.9 Hz), 7.23 (1H, d, J=2.2 Hz), 5.35 (1H, br. s.), 3.59 (2H, td, J=6.8, 1.9 Hz), 2.86 (2H, t, J=7.0 Hz), 2.64 (3H, s), 2.29 (3H, s). m/z (ESI, +ve) 370.0 (M+H)+.

Workup

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

Sources & evidence

ORD record
ord-518ff6d187d0478384d0634c9b5f4796
Source dataset
uspto-grants-2016_07
Patent number
US09394297B2

Reaction notes

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