Hydrochloric Acid → 2-N-(3-Aminopropyl)-amino-5-bromopyridine

A mixture of 1,3-diaminopropane (17.6 ml), 2,5-dibromopyridine (10 g) and pyridine (5 ml) was heated under reflux for 4 hr. After stripping off the excess of 1,3-diaminopropane, the residue was taken up in water, the pH adjusted to 7 (conc. hydrochloric acid) and the solution extracted with chloroform. The pH was raised to 14 and extracted with chloroform. After drying (K2CO3), the final extract was evaporated to give 2-(3-aminopropylamino)-5-bromopyridine (9.1 g) as an oil which was used without further purification. (ii) To a suspension of sodium hydride (0.3 g) in DMSO (20 ml) was added 2-(3-aminopropylamino)-5-bromopyridine (2.88 g). The mixture was stirred and heated slowly to 85° C. After the evolution of hydrogen had ceased the mixture was cooled to room temperature and methyl iodide (1.77 g) in DMSO (5 ml) added dropwise maintaining the temperature below 30° C. After a further 15 min water (150 ml) was added and the mixture extracted with chloroform. The chloroform extract was washed with water and extracted with 1N hydrochloric acid. The acid extract was washed with chloroform, the pH adjusted to 13 (2N NaOH) and extracted again with chloroform. The final extract was stripped and the residue chromatographed (silica gel, 5% ammoniacal methanol/dichloromethane) to give 2-[N-(3-aminopropyl)-N-methylamino]-5-bromopyridine (1.44 g) as an oil which was used without further purification. (iii) 2-[N-(3-aminopropyl)-N-methylamino]-5-bromopyridine (1.4 g) and 2-nitroamino-5-(6-methylpyrid-3-ylmethyl)pyrimid-4-one (1.25 g) were heated together under reflux in pyridine (10 ml) for 20 hr. After stripping, the residue was triturated with wet ether and recrystallised from isopropanol/water to give 2-[3-[N-methyl-N-(5-bromopyrimid-2-yl)amino]propylamino]-5-(6-methylpyrid-3-yl-methyl)pyrimid-4-one, 1.5 g (71%) mp 137°-40° C.

1. temperaturewas heated
2. temperatureunder reflux for 4 hr
3. extractionthe solution extracted with chloroform
4. temperatureThe pH was raised to 14
5. extractionextracted with chloroform
6. dry with materialAfter drying (K2CO3)
7. extractionthe final extract
8. customwas evaporated

ORD record

ord-79f79e0e2ef3427994ec9adefb87896d

Source dataset

uspto-grants-1985_10

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US04547506