Oxalyl chloride → 10a-(4-methoxyphenyl)-1-[(3-methyl-1,2-oxazol-4-yl)carbonyl]-5-oxo-2,3,10,10a-tetrahydro-1H,5H-imidazo[1,2-a]pyrrolo[1,2-d]pyrazine-8-carbonitrile

Participants

Reaction Conditions

Reaction Steps

To generate the acid chloride, oxalyl chloride (150 μL, 1.61 mmol) and DMF (1 drop) were added to a suspension of 3-methyl-1,2-oxazole-4-carboxylic acid (65 mg, 0.51 mmol) in CH2Cl2 (1 mL) at 0° C. The suspension was allowed to stir for a further 15 minutes at 0° C. followed by 1 hour at room temperature. The resulting solution was concentrated in vacuo (without heating) to give an oil that was dissolved in CH2Cl2 and concentrated in vacuo. To a chilled (ice bath) suspension of the acid chloride (generated as above, 0.51 mmol) in pyridine (1 mL) was added a cloudy mixture of 10a-(4-methoxyphenyl)-5-oxo-2,3,10,10a-tetrahydro-1H,5H-imidazo[1,2-a]pyrrolo[1,2-d]pyrazine-8-carbonitrile (45 mg, 0.1 mmol) in pyridine (1 mL). The reaction mixture was warmed to room temperature and stirred for 1.5 hour. The reaction mixture was then diluted with water (5 mL) and extracted with CH2Cl2 (3×2 mL). The organic fractions were combined, dried (MgSO4) and concentrated in vacuo to yield a crude residue that was purified by flash chromatography (Biotage SP4, 4 g cartridge, gradient 0-100% EtOAc in hexanes) and reverse phase chromatography (Biotage SP4, 12 g cartridge, C18, 5-50s-55-100% acetonitrile in water; water contained 0.1% formic acid) to give 10a-(4-methoxyphenyl)-1-[(3-methyl-1,2-oxazol-4-yl)carbonyl]-5-oxo-2,3,10,10a-tetrahydro-1H,5H-imidazo[1,2-a]pyrrolo[1,2-d]pyrazine-8-carbonitrile (106) as a white solid (17 mg, yield 40%).

Provenance & Evidence