4-Aminophenol → 4-(2-(N-(2-morpholin-4-ylethyl)carbamoyl)pyridyloxy)aniline

Temperature

75 °C

A solution of 4-aminophenol (0.49 g, 4.52 mmol) and potassium tert-butoxide (0.53 g, 4.75 mmol) in DMF (8 mL) was stirred at room temp. for 2 h, then was sequentially treated with 4-chloro-2-(N-(2-morpholin-4-ylethyl)carbamoyl)pyridine (1.22 g, 4.52 mmol) and K2CO3 (0.31 g, 2.26 mmol). The resulting mixture was heated at 75° C. overnight, cooled to room temp., and separated between EtOAc (25 mL) and a saturated NaCl solution (25 mL). The aqueous layer was back extracted with EtOAc (25 mL). The combined organic layers were washed with a saturated NaCl solution (3×25 mL) and concentrated under reduced pressure. The resulting brown solids were purified by column chromatography (58 g; gradient from 100% EtOAc to 25% MeOH/75% EtOAc) to afford 4-(2-(N-(2-morpholin-4-ylethyl)carbamoyl)pyridyloxy)aniline (1.0 g, 65%): TLC (10% MeOH/90% EtOAc) Rf 0.32.

1. temperaturecooled to room temp.
2. customseparated between EtOAc (25 mL)
3. extractionThe aqueous layer was back extracted with EtOAc (25 mL)
4. washThe combined organic layers were washed with a saturated NaCl solution (3×25 mL)
5. concentrationconcentrated under reduced pressure
6. customThe resulting brown solids were purified by column chromatography (58 g; gradient from 100% EtOAc to 25% MeOH/75% EtOAc)

ORD record

ord-98d83caceb944dfcb4d500d9e5a88671

Source dataset

uspto-grants-2012_02

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08124630B2