Oxalic Acid → HCID 86753237, compound

Participants

Reaction Steps

Intermediate 16-a (0.072 mol) was dissolved in methylbenzene (250 ml)/H (100 ml). The solution was cooled to -70° C. Diisobutylaluminium hydride, 1.5M solution in hexane (0.1 mol) was added dropwise and the mixture was stirred for 1 hour at -70° C. Methanol (15 ml) was added dropwise and the reaction mixture was allowed to warm to room temperature. The mixture was poured out into water, acidified with hydrochloric acid and extracted with diethyl ether. The separated organic layer was dried, filtered and the solvent evaporated. The residue was dissolved in methanol (150 ml). N-2-pyrimidinyl-1,3-propanediamine (0.06 mol) was added and the mixture was hydrogenated with palladium-on-charcoal (small amount) as a catalyst in the presence of thiophene, 4% solution (10 ml). After uptake of H2 (1 equiv), the catalyst was filtered off and the filtrate was evaporated. The residue was purified by column chromatography over silica gel (eluent: CH2Cl2 /CH3OH 90/10). Three fraction groups were collected and the solvent was evaporated, yielding residues (1), (2) and (3) (12 g). A sample of residue (3) (3.6 g) was dissolved in 2-propanone and converted into the ethanedioic acid salt (1:2) with a solution of ethanedioic acid.H2O (0.020 mol) in 2-propanone. The precipitate was filtered off and dried, yielding 4.5 g (46.1%) of (±)-N-[(7,8-dihydro-2,3-dimethyl-6H-furo[3,2-h][1]benzopyran-8-yl)methyl]-N'-2-pyrimidinyl-1,3-propanediamine ethanedioate(1:2); mp. 208.8° C. (comp. 7-a). Residue (2) was repurified by column chromatography over silica gel (eluent: CH2Cl2 /CH3OH 85/15). The desired fractions were collected and the solvent was evaporated. The residue (1.8 g) was dissolved in ethanol and converted into the ethanedioic acid salt (1:2) with ethanedioic acid (0.010 mol). The precipitate was filtered off and dried, yielding 1.1 g (3.3%) (±)-N-2-pyrimidinyl-N'-[(3,6,7,8-tetrahydro-2,3-dimethyl-2H-furo[3,2-h][1]benzopyran-8-yl)methyl]-1,3-propanediamine ethanedioate (1:2); mp. 171.2° C. (comp. 8-a).

Provenance & Evidence