Pyridine → [(1R)-1-cyclopropylethyl] N-[4-(3-cyano-1-cyclopropyl-6-pyrimidin-2-yloxy-indol-2-yl)phenyl]carbamate

Temperatur

30 °C

A mixture of 2-(6-amino-pyridin-3-yl)-1-cyclobutyl-6-(pyrimidin-2-yloxy)-1H-indole-3-carbonitrile (115 mg, 0.3 mmol), 4-nitrophenylchloroformate (91 mg, 0.45 mmol) in pyridine (1.0 mL) was stirred at 30° C. for 2 h, followed by the addition of (R)-1-cyclopropylethanol (150 μL, 1.5 mmol). The mixture was stirred at 80° C. overnight and diluted with water (10 mL) and CH2Cl2 (5 mL). The organic layer was washed with water (3×5 mL), HCl (2N, 3×5 mL), sat. aq. NaHCO3 (3×5 mL) and and purified on silica gel (CH2Cl2/EtOAc, 1:9) to provide (R)-{4-[3-cyano-1-cyclopropyl-6-(pyrimidin-2-yloxy)-1H-indol-2-yl]-phenyl}-carbamic acid 1-cyclopropylethyl ester (25 mg, 17%).

1. stirringThe mixture was stirred at 80° C. overnight
2. washThe organic layer was washed with water (3×5 mL), HCl (2N, 3×5 mL), sat. aq. NaHCO3 (3×5 mL)
3. custompurified on silica gel (CH2Cl2/EtOAc, 1:9)

ORD-Eintrag

ord-448c2c567cac41faa6afb564b97a55d8

Quelldatensatz

uspto-grants-2010_08

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US07772271B2