Triethylamine → HCID 67350460, compound

Participants

Reaction Conditions

Reaction Steps

(S)-3-(9-Methylthio-6-oxo-2,3,3a,4-tetrahydro-1H,6H-5,8,10,10b-tetraazabenzo[e]azulen-5-yl)benzoic acid (2.00 g, 5.40 mmol) obtained in Step 1 of Example 56 was dissolved in dichloromethane (80 mL), and the mixture was stirred for 4 hours after adding L-threonine methyl ester hydrochloride (3.11 g, 16.2 mmol), triethylamine (2.26 mL, 16.2 mmol), 1-ethyl-3-(3dimethylaminopropyl)carbodiimide hydrochloride (1.24 g, 6.48 mmol), and 1-hydroxybenzotriazole.monohydrate (827 mg, 5.40 mmol). The mixture was diluted by addition of chloroform, and washed with a saturated aqueous sodium bicarbonate solution. The organic layer was dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The resulting residue was dissolved in dichloromethane (80 mL), cooled to 0° C., and stirred at room temperature for 4.5 hours after adding thionyl chloride (2.85 mL, 3.91 mmol). Then, the mixture was poured into a saturated aqueous sodium bicarbonate solution, and extracted with chloroform. The organic layer was then dried over anhydrous magnesium sulfate, and concentrated under reduced pressure to give methyl (4S,5S)-5-methyl-2-[3-((S)-9-methylthio-6-oxo-2,3,3a,4-tetrahydro-1H,6H-5,8,10,10b-tetraazabenzo[e]azulen-5-yl)phenyl]-4,5-dihydro-1,3-oxazole-4-carboxylate as a crude product. Using methyl (4S,5S)-5-methyl-2-[3-((S)-9-methylthio-6-oxo-2,3,3a,4-tetrahydro-1H,6H-5,8,10,10b-tetraazabenzo[e]azulen-5-yl)phenyl]-4,5-dihydrooxazole-4-carboxylate so obtained, methyl (S)-5-methyl-2-[3-(9-methylthio-6-oxo-2,3,3a,4-tetrahydro-1H,6H-5,8,10,10b-tetraazabenzo[e]azulen-5-yl)phenyl]-1,3-oxazole-4-carboxylate (2.04 g, 81%) was obtained in the same manner as in Step 2 of Example 123.

Provenance & Evidence