2,6-Diaminopyridine → N2-(6-chloropyrimidin-4-yl)pyridine-2,6-diamine

Temperature

100 °C

A mixture of 2,6-diaminopyridine (1.530 g, 14.020 mmol) and 4,6-dichloropyrimidine (2.610 g, 17.519 mmol) in 15 mL of n-butanol in a sealed vial was heated at 100° C. for 72 h. The dark brown sample was cooled and was concentrated at reduced pressure to remove most of the n-butanol. The residue was then partitioned between EtOAc and saturated. NaHCO3 solution. An emulsion formed, the sample was filtered through a pad of Celite and the layers were separated. The organic extract was washed with sat. KH2PO4 and brine solutions, dried (MgSO4), filtered and concentrated to brown oily-solid. The sample was suspended into ˜50 mL of CH2Cl2, cooled and filtered to give 1.017 g (36%) of N-(6-chloro-pyrimidin-4-yl)-pyridine-2,6-diamine as yellow-orange solid. MS: m/z 222/224 (M+1, 100/63%). To a solution of N-(6-chloro-pyrimidin-4-yl)-pyridine-2,6-diamine (100 mg, 0.45 mmol) in DMF (1 mL) was added 3-methylphenol (88 mg, 0.8 mmol) and anhydrous K2CO3 (93 mg, 0.6 mmol). The reaction mixture was heated at 145° C. for 16 h. It was then cooled and DMF was removed under reduced pressure to get a yellow gummy residue. The residue was taken in EtOAc (20 mL), was washed sequentially with water (5 mL) and brine (5 mL) and was dried over Na2SO4. Filtration followed by concentration under reduced pressure afforded a yellow gum which was further purified by column chromatography (SiO2, 60-120, EtOAc/hexane, 5/5) to give 100 mg of 2-[6-(3-methylphenoxy)-pyrimidin-4-yl]amino-6-aminopyridine (IR-12) as a pale yellow solid. MS: m/z 294 (M+H)

1. temperatureThe dark brown sample was cooled
2. concentrationwas concentrated at reduced pressure
3. customto remove most of the n-butanol
4. customThe residue was then partitioned between EtOAc
5. customAn emulsion formed
6. filtrationthe sample was filtered through a pad of Celite
7. customthe layers were separated
8. extractionThe organic extract
9. washwas washed with sat. KH2PO4 and brine solutions
10. dry with materialdried (MgSO4)
11. filtrationfiltered
12. concentrationconcentrated to brown oily-solid
13. temperaturecooled
14. filtrationfiltered

ORD record

ord-5b1ac64267a04f729d2f4cc580a34a2e

Source dataset

uspto-grants-2011_08

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07989465B2