Triethylamine → 6-Methoxy-8-piperazin-1-yl-[1,7]naphthyridine

Temperature

80 °C

A solution of 6-methoxy-[1,7]naphthyridin-8-ylamine (2.25 g, 12.8 mmol), bis(2-chloroethyl)-benzlyamine (10.25 g, 38.6 mmol) and Et3N (5.34 mL, 38.6 mmol) in BuOH (100 mL) was heated at 100° C. for 72 hours. The cooled reaction mixture was poured into H2O (100 mL) and 2.5 N NaOH (100 mL), and extracted into EtOAc (2×200 mL). The organic phases were combined, dried over Na2SO4, filtered and concentrated. The resulting oil was purified twice by column chromatography (10% MeOH/CH2Cl2) affording a dark gold oil with BuOH impurity. This oil was dissolved in EtOH (50 mL) and 10% Pd/C (390 mg) and ammonium formate (730 mg) was added. The reaction mixture was heated at 80° C. for 2.5 hours. The cooled reaction mixture was filtered through a pad of celite and washed with EtOAc (50 mL). The organic phase was concentrated and purified by column chromatography (10% MeOH/CH2Cl2+NH4OH) affording 270 mg of the title compound as a dark orange oil. An analytical sample was prepared as the HCl salt from EtOAc.

1. customThe cooled reaction mixture
2. extractionextracted into EtOAc (2×200 mL)
3. dry with materialdried over Na2SO4
4. filtrationfiltered
5. concentrationconcentrated
6. customThe resulting oil was purified twice by column chromatography (10% MeOH/CH2Cl2)
7. customaffording a dark gold oil with BuOH impurity
8. customThe cooled reaction mixture
9. filtrationwas filtered through a pad of celite
10. washwashed with EtOAc (50 mL)
11. concentrationThe organic phase was concentrated
12. custompurified by column chromatography (10% MeOH/CH2Cl2+NH4OH)

ORD record

ord-41f7f072f1ef4f5d82adaced5d50e652

Source dataset

uspto-grants-2002_10

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06465482B2