Trimethyl orthoformate → 3-[1-(4-carbamoyl-2-methylphenyl)-5-(4-tetrazol-1-yl-phenyl)-1H-pyrrol-2-yl]-propionic acid ethyl ester

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Reaction Steps

Under a nitrogen atmosphere, 3-[5-(4-aminophenyl)-1-(4-carbamoyl-2-methylphenyl)-1H-pyrrol-2-yl]-propionic acid ethyl ester (11A, synthesis described in Scheme 4 where R1=4-carbamoyl-2-methylphenyl) (102 mg, 0.26 mmol) was dissolved in 2 mL glacial acetic acid. Trimethylorthoformate (0.1 mL, 0.78 mmol) was added. The mixture was stirred for 20 min. at room temperature. Sodium azide (25 mg, 0.39 mmol) was added and the reaction was heated to 80° C. for 2 hrs. After cooling, the reaction was diluted with water (3 mL) and extracted with ethyl acetate. The combined organic layers were washed with brine, dried over Na2SO4, filtered and concentrated in vacuo. The crude material was purified by preparative TLC plate (1500 microns, 10% IPA/CH2Cl2). The desired band (rf=0.5) was isolated and dried under high vacuum to yield 3-[1-(4-carbamoyl-2-methylphenyl)-5-(4-tetrazol-1-yl-phenyl)-1H-pyrrol-2-yl]-propionic acid ethyl ester (12B) (71 mg, 60%, light orange powder).

Provenance & Evidence