反应详情

温度

165 °C

A solution of 3-bromo-9H-dipyrido[2,3-b;4′,3′-d]pyrrole-6-carbonitrile (100 mg, 0.366 mmol) and lithium chloride (46.6 mg, 1.10 mmol) in DMF (0.63 mL) was treated with DIPEA (159 uL, 0.915 mmol) and 2-(tri-n-butylstannyl)thiazole (345 uL, 1.10 mmol), and then degassed by the bubbling of nitrogen for 5 minutes. Tetrakis(triphenylphosphine)palladium(0) (21.2 mg, 18.3 umol, 5.0 mol %) was added and the mixture heated at 165° C. for 15 hours. The mixture was allowed to cool and treated with saturated aqueous potassium fluoride solution at ambient temperature. The resulting solids were removed by filtration and washed with 20% methanol in DCM and water. The filtrate was filtered through a pad of celite, washing with 20% methanol in DCM. The layers were separated, the aqueous phase extracted into 20% methanol in DCM, and the combined organic phases concentrated in vacuo. The residue was dissolved in AcOH with sonication and heating, filtered hot and allowed to cool. The resulting suspension was treated with water and then filtered to collect the off-white solid. This solid was purified by preparative HPLC [0-30% MeCN/water modified with 0.1% formic acid] to afford an off-white solid powder (5.0 mg, 18%). 1H NMR (400 MHz, DMSO-D6): 9.26 (s, 1H), 9.24 (s, 1H), 9.01 (s, 1H), 8.94 (s, 1H), 7.96 (d, J=3.2 Hz, 1H), 7.80 (d, J=3.2 Hz, 1H). LCMS (Method D): RT=9.31 min, M+H+=278.

1. customdegassed by the
2. custombubbling of nitrogen for 5 minutes
3. temperatureto cool
4. customThe resulting solids were removed by filtration
5. washwashed with 20% methanol in DCM and water
6. filtrationThe filtrate was filtered through a pad of celite
7. washwashing with 20% methanol in DCM
8. customThe layers were separated
9. extractionthe aqueous phase extracted into 20% methanol in DCM
10. concentrationthe combined organic phases concentrated in vacuo
11. dissolutionThe residue was dissolved in AcOH with sonication
12. temperatureheating
13. filtrationfiltered hot
14. temperatureto cool
15. additionThe resulting suspension was treated with water
16. filtrationfiltered
17. customto collect the off-white solid
18. customThis solid was purified by preparative HPLC [0-30% MeCN/water modified with 0.1% formic acid]