Diisopropylamine → 5-Amino-2,3-dihydrothiazolo[3,2-a]pyridin-7-one

Participants

Reaction Steps

To a solution of lithium diisopropylamide (LDA), prepared from n-BuLi (106.6 ml, 0.16M) and diisopropylamine (16.7 g, 23.1 ml, 0.16M), in dry THF (100 ml) was added under N2 at -10° C., 5-methylisoxazole (6.8 g, 0.08M). The resultant yellow suspension was mechanically stirred at -10° C. for 30 min before the 4,5-dihydro-2-methylthiothiazole (11 g, 0.08M) was added dropwise. After the addition was complete, an orange oil separated, and the mixture was allowed to warm to ambient over a period of 20 hr. A mixture of MeOH (60 ml) and glacial acetic acid (4.5 ml, 0.08M) was slowly added and the resultant reddish solution was stirred at ambient overnight. The solvents were evaporated in vacuo, and the residual oil was flash column chromatographed on silica gel (EM-60) with 30% MeOH in CH2Cl2 as the eluent to give the desired amine (7 g), which was further recrystallized from MeOH/Et2O to give the title compound (5.4 g, 40%), mp>241° C. TLC (30% MeOH in CH2Cl2); Rf=0.33. IR (KBr) cm1, 3350-3000 (broad), 1675, 1625.

Provenance & Evidence