Potassium Carbonate → 7-(3-Bromo-phenyl)-2-chloro-5H-pyrrolo[2,3-b]pyrazine

A 50 ml round bottom flask was charged under nitrogen with 2-chloro-7-iodo-5-(toluene-4-sulfonyl)-5H-pyrrolo[2,3-b]pyrazine (6) (950 mg, 2.2 mmol), 3-bromophenyl boronic acid (440 mg, 2.2 mmol), tetrakis-triphenylphosphine palladium (50 mg, 0.04 mmol), 2M aqueous potassium carbonate (2.2 ml, 4.4 mmol) in a toluene/ethanol mixture (15/3 ml) under nitrogen. The reaction mixture was refluxed for 18 h, then allowed to cool to room temperature. The solution was diluted with ethyl acetate (˜70 ml). The organic was washed with brine, dried over magnesium sulfate and concentrated in vacuo, The residue was triturated in dichloromethane/methanol. A pale yellow solid was removed by filtration (300 mg). The residue was taken up in a tetrahydrofuran/methanol/1M NaOH mixture (4/1/1 ml) and stirred at room temperature for 2 h. The reaction mixture was diluted with ethyl acetate, washed with brine, dried over magnesium sulfate and concentrated in vacuo. The residue was triturated in methanol. A solid was filtered off as the title compound (10 mg, 1%). 1H NMR (DMSO-d6): 7.35-7.45 (2H, m), 8.10-8.15 (1H, d), 8.35 (1H, s), 8.4 (1H, s), 8.6 (1H, s). MS (ES+): 310, 312.

1. temperatureThe reaction mixture was refluxed for 18 h
2. washThe organic was washed with brine
3. dry with materialdried over magnesium sulfate
4. concentrationconcentrated in vacuo
5. customThe residue was triturated in dichloromethane/methanol
6. customA pale yellow solid was removed by filtration (300 mg)
7. additionThe reaction mixture was diluted with ethyl acetate
8. washwashed with brine
9. dry with materialdried over magnesium sulfate
10. concentrationconcentrated in vacuo
11. customThe residue was triturated in methanol
12. filtrationA solid was filtered off as the title compound (10 mg, 1%)

ORD record

ord-d1a4802f3dc74e79a288c2a0190297e4

Source dataset

uspto-grants-2013_02

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08372835B2