Sodium Carbonate → HCID 89784085, compound

HRID 1056281Notes

Reaction equation

HRID 1056281 reaction equation
C([O-])([O-])=O.[Na+].[Na+].[Cl:7][C:8]1[C:13](B(O)O)=[CH:12][CH:11]=[CH:10][N:9]=1.Cl[C:18]1[C:19]([CH3:38])=[N:20][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>>[Cl:7][C:8]1[C:13]([C:18]2[C:19]([CH3:38])=[N:20][C:21]3[C:26]([N:27]=2)=[C:25]([C:28]2[NH:36][C:35]4[CH2:34][CH2:33][NH:32][C:31](=[O:37])[C:30]=4[CH:29]=2)[CH:24]=[CH:23][CH:22]=3)=[CH:12][CH:11]=[CH:10][N:9]=1

Participants

4

Reactant 3

HCID 10340Sodium CarbonateHCID 2762704(2-Chloropyridin-3-yl)boronic acidHCID 897835202-(3-chloro-2-methylquinoxalin-5-yl)-6,7-dihydro-1H-pyrrolo[3,2-c]pyridin-4(5H)-one

Product 1

HCID 89784085HCID 89784085, compoundYield 4%

Conditions

Temperature
100 °C

Procedure

A mixture of Na2CO3 (102 mg, 0.959 mmol), Pd(Ph3)4 (18.47 mg, 0.016 mmol; Strem Chemicals), (2-chloropyridin-3-yl)boronic acid (75 mg, 0.480 mmol; Alfa Aesar, Ward Hil, Mass.), and 2-(3-chloro-2-methylquinoxalin-5-yl)-6,7-dihydro-1H-pyrrolo[3,2-c]pyridin-4(5H)-one (100 mg, 0.320 mmol, 254c) was added to a conical vessel, sealed, and evacuated and backfilled with nitrogen three times. 1,4-dioxane (2.4 mL) and water (0.8 mL) were added via syringe, and the reaction was heated to 100° C. overnight. The reaction was cooled to RT and concentrated under reduced pressure to a residue. The residue was taken up in 2 mL DMSO, filtered through a syringe filter, and purified by reverse-phase preparative HPLC using a Xbridge C18 column (150 mm×30 mm, 10 mm), 40 mL min with 0.1% TFA in CH3CN/H2O, gradient 25% to 75% over 12 min. The product fractions were concentrated in a Genevac EZ-2 evaporator. The resulting solids were taken up in MeOH and eluted through a Si-carbonate cartridge (Silicycle, pre-washed with MeOH). The eluent was concentrated under reduced pressure to give 2-(3-(2-chloro-3-pyridinyl)-2-methyl-5-quinoxalinyl)-1,5,6,7-tetrahydro-4H-pyrrolo[3,2-c]pyridin-4-one (5 mg, 4%). 1H NMR (400 MHz, DMSO-d6) δ ppm 11.72 (1H, s) 8.84-8.98 (1H, m) 8.79 (1H, d, J=4.89 Hz) 8.08 (1H, dd, J=5.97, 2.64 Hz) 7.89-7.95 (2H, m) 7.82 (1H, d, J=4.89 Hz) 7.16-7.23 (1H, m) 7.01 (1H, br. s.) 3.33-3.43 (2H, m) 2.83 (2H, t, J=6.94 Hz) 2.54 (3H, s) m/z (ESI, +ve) 390.8 (M+H)+.

Workup

  1. additionwas added to a conical vessel
  2. customsealed
  3. customevacuated
  4. addition1,4-dioxane (2.4 mL) and water (0.8 mL) were added via syringe
  5. temperatureThe reaction was cooled to RT
  6. concentrationconcentrated under reduced pressure to a residue
  7. filtrationfiltered through a syringe
  8. filtrationfilter
  9. custompurified by reverse-phase preparative HPLC
  10. customover 12 min
  11. concentrationThe product fractions were concentrated in a Genevac EZ-2 evaporator
  12. washeluted through a Si-carbonate cartridge (Silicycle, pre-washed with MeOH)
  13. concentrationThe eluent was concentrated under reduced pressure

Sources & evidence

ORD record
ord-31c6004b09454a3990e2bcf0c5cf36c4
Source dataset
uspto-grants-2016_07
Patent number
US09394297B2

Reaction notes

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