1-Hydroxybenzotriazole → 2-Amino-4-[3-(pyrimidin-2-ylcarbamoyl)-propyl]-imidazole-1-carboxylic acid tert-butyl ester

General EDC/HOBt procedure: 2-amino-4-(3-carboxy-propyl)-imidazole-1-carboxylic acid tert-butyl ester 22 (100 mg, 0.371 mmol), 1-hydroxybenzotriazole (100 mg, 0.742 mmol) and N-(3-dimethylaminopropyl)-N′-ethylcarbodiimide hydrochloride (142 mg, 0.742 mmol) were dissolved in anhydrous DMF (3 mL). The appropriate amine coupling partner (1.48 mmol) was then added and the solution was stirred at ambient temperature until completion was evident by TLC analysis. The reaction was concentrated under reduced pressure and the residue partitioned between ethyl acetate (20 mL) and water (10 mL). The organic layer was successively washed with water (3×10 mL), a 10% aqueous solution of citric acid (2×10 mL), sat. NaHCO3 (2×10 mL), and brine (10 mL) before being dried (Na2SO4) and evaporated to dryness. The crude product was purified via flash column chromatography (2-10% MeOH/CH2Cl2) to afford the target compound.

1. concentrationThe reaction was concentrated under reduced pressure
2. customthe residue partitioned between ethyl acetate (20 mL) and water (10 mL)
3. washThe organic layer was successively washed with water (3×10 mL)
4. dry with materiala 10% aqueous solution of citric acid (2×10 mL), sat. NaHCO3 (2×10 mL), and brine (10 mL) before being dried (Na2SO4)
5. customevaporated to dryness
6. customThe crude product was purified via flash column chromatography (2-10% MeOH/CH2Cl2)
7. customto afford the target compound

ORD 기록

ord-fce722cae1ab4927a42ab1932d6e51d0

출처 데이터셋

uspto-grants-2012_10

DOI

10.6084/m9.figshare.5104873.v1

특허 번호

US08278340B2