4-Methylmorpholine → N-{[4-((2R,3R)-1-(4-Fluorophenyl)-3-{[2-hydroxy-2-(4-pentylphenyl)ethyl]thio}-4-oxoazetidin-2-yl)phenoxy]acetyl}glycyl-3-cyclohexyl-D-alanine

Temperatur

30 °C

To a solution of [4-((2R,3R)-1-(4-fluorophenyl)-4-oxo-3-{[2-oxo-2-(4-pentylphenyl)ethyl]thio}azetidin-2-yl)phenoxy]acetic acid (0.020 g, 0.037 mmol) and NMM (0.012 ml, 0.109 mmol) in DMF (2 ml) at 30° C. was added TBTU (0.019 g, 0.059 mmol). After 15 min glycyl-3-cyclohexyl-D-alanine (0.009 g, 0.039 mmol) was added and the mixture was stirred at 30° C. for 22 h. The reaction was quenched by the addition of water (1 ml) before the mixture was diluted with MeOH (2 ml). To this solution was added NaBH4 (0.020 g, 0.529 mmol) and the mixture was stirred for 10 min. This reaction was quenched by the addition of a 0.1M ammonium acetate buffer (3 ml) and most of the methanol was removed under reduced pressure. The remaining solution was purified by preparative HPLC using a gradient of 20-60% MeCN in a 0.1M ammonium acetate buffer as eluent. Freeze-drying of the pure fractions gave the desired product as a white solid (0.009 g, 32% yield).

1. customThe reaction was quenched by the addition of water (1 ml) before the mixture
2. additionwas diluted with MeOH (2 ml)
3. stirringthe mixture was stirred for 10 min
4. customThis reaction was quenched by the addition of a 0.1M ammonium acetate buffer (3 ml) and most of the methanol
5. customwas removed under reduced pressure
6. customThe remaining solution was purified by preparative HPLC
7. customFreeze-drying of the pure fractions

ORD-Eintrag

ord-3efdf76d363d49538af4ca105e8c3590

Quelldatensatz

uspto-grants-2011_01

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US07871998B2