反应详情

1-methylpiperazine (2.109 g, 21.06 mmol) in DCM (62.50 mL) was added to a stirred solution of 3-bromo-4-chloro-5-nitro-pyridine (5000 mg, 21.06 mmol) and DIPEA (3.266 g, 4.402 mL, 25.27 mmol) in DCM (62.50 mL) at RT. The reaction was allowed to stir at ambient temperature for 2 h, then was concentrated in vacuo. The residue was partitioned between a saturated aqueous solution of NaHCO3 and DCM. Combined organic extract was dried and concentrated in vacuo. The orange solid was suspended in Acetic acid (60.00 mL) before iron (7.059 g, 126.4 mmol) was added. The mixture was warmed at 50° C. and stirred for 15 min. The mixture was allowed to cool to RT and DCM:EtOAc (4:1) (400 mL) was added to the reaction. The resulting brown suspension was filtered using a prewetted Celite cartridge (25 g), washing with more DCM:MeOH (4:1) (200 mL). Combined filtrate was concentrated in vacuo to afford a red/brown gum which was purified by chromatography on silica (Rf companion, 80 g cartridge), eluting with DCM-DCM:MeOH:NE3(90:10:1) a gradient of 100-0 to 20:80. Fractions containing clean product were collected and concentrated in vacuo to afford 5-bromo-4-(4-methylpiperazin-1-yl)pyridin-3-amine as a viscous, clear light yellow oil that solidifies on standing. MS (ES+) 273.1.

1. concentrationwas concentrated in vacuo
2. customThe residue was partitioned between a saturated aqueous solution of NaHCO3 and DCM
3. extractionCombined organic extract
4. customwas dried
5. concentrationconcentrated in vacuo
6. additionwas added
7. temperatureThe mixture was warmed at 50° C.
8. stirringstirred for 15 min
9. temperatureto cool to RT
10. filtrationThe resulting brown suspension was filtered
11. washwashing with more DCM:MeOH (4:1) (200 mL)
12. concentrationCombined filtrate was concentrated in vacuo
13. customto afford a red/brown gum which
14. customwas purified by chromatography on silica (Rf companion, 80 g cartridge)
15. washeluting with DCM-DCM
16. additionFractions containing clean product
17. customwere collected
18. concentrationconcentrated in vacuo