Putrescine → N-(4-aminobutyl)pyridin-2-amine

Participants

Reaction Steps

2-Bromopyridine (10 g), 1,4-diaminobutane (35 ml) and pyridine (7 ml) were heated together under reflux for 4 hr. The mixture was stripped to remove the excess of diaminobutane and the residue taken up in water. The solution was extracted with chloroform at pH 7 and 13. After drying (K2CO3) the latter extract was stripped and the residue distilled at reduced pressure to give 2-(4-amino-butylamino) pyridine 7.0 g (67%) bp 136°-38° C., 2 mm Hg. (ii) A mixture of sodium hydride (0.78 g) and 2-(4-aminobutylamino) pyridine (4.9 g) in DMSO (45 ml) was heated slowly to 85° C. under nitrogen. After the evolution of hydrogen had ceased the solution was cooled to room temperature and methyl iodide (2.1 ml) in DMSO (10 ml) added dropwise below 25° C. After a further 1.5 hr the mixture was poured into water (150 l) and extracted with dichloromethane. The volume of the extract was reduced and washed with 2N hydrochloric acid. Partitioning between water, ether and dichloromethane at pH 1 and 13 gave, on stripping the final basic extract, 2-[N-(4-aminobutyl)-N-methylamino]pyridine (3.22 g) as an oil which was used without further purification. (iii) 2-[N-(4-aminobutyl)-N-methylamino]pyridine (0.81 g) and 2-methylthio-5-(4-chlorobenzyl)pyrimid-4-one (1.0 g) were heated together under reflux in pyridine (2.5 ml) for 23 hr. After stripping, the residue was crystallised twice from ethanol/water to give 2-[4-(N-methyl-N-pyrid-2-ylamino)butylamino]-5-(4-chlorobenzyl)pyrimid-4-one 1.5H2O, 0.98 g (62%) mp softens 72-75 melts 133°-35° C.

Provenance & Evidence