Methane → N-(4-methyl-2-pyridyl)-3-(3-pyridyl)-1H,3H-pyrrolo[1,2-c]thiazole-7-carboxamide

Participants

Reaction Conditions

Reaction Steps

The hydrochloride of the acid chloride derived from (+)-3-(3-pyridyl)-1H,3H-pyrrolo[1,2-c]thiazole-7-carboxylic acid (12 g) is added, at a temperature between 65° and 72° C., to a solution of 2-amino-4-methylpyridine (4.3 g) and triethylamine (8.1 g) in dioxane (300 cc) which is heated to a temperature in the vicinity of 60° C., in the course of 5 minutes. The suspension obtained is heated, with stirring, at a temperature in the vicinity of 100° C. for 7 hours and then stirred at a temperature in the vicinity of 20° C. for 16 hours. The solvent is evaporated off under reduced pressure (20 mm Hg; 2.7 kPa) at a temperature in the vicinity of 60° C. The residue is dissolved in methylene chloride (500 cc). The solution obtained is washed twice with distilled water (300 cc in total), twice with a saturated aqueous sodium bicarbonate solution (300 cc in total) and twice with distilled water (300 cc in total) and then dried over anhydrous magnesium sulphate, treated with decolorizing charcoal (0.5 g), filtered and concentrated to dryness under reduced pressure (20 mm Hg; 2.7 kPa) at a temperature in the vicinity of 60° C. A crude product (13.3 g) is thereby obtained, which is dissolved in boiling acetonitrile (140 cc). Decolorizing charcoal (0.5 g) is added to the solution obtained and the suspension is filtered in the heated state. The filtrate is cooled at a temperature in the vicinity of 20° C. for 2 hours. The crystals formed are separated by filtration, washed 3 times with acetonitrile (75 cc in total) add 3 times with diethyl ether (90 cc in total) and then dried under reduced pressure (20 mm Hg; 2.7 kPa) at a temperature in the vicinity of 20° C. in the presence of potassium hydroxide pellets. (+)-N-(4-methyl-2-pyridyl)-3-(3-pyridyl)-1H,3H-pyrrolo[1,2-c]thiazole-7-carboxamide (3.1 g) in the form of cream-coloured crystals, m.p. 174° C., is thereby obtained. ([α]D20 =+82°±0.9°; c=1.09; dimethylformamide).

Provenance & Evidence