Phosphorus oxychloride → Ethyl 4-chloro-5-methylpyrrolo[2,1-f][1,2,4]triazine-6-carboxylate

A mixture of 4-hydroxy-5-methylpyrrolo[2,1-f][1,2,4]triazine-6-carboxylic acid ethyl ester (60.0 g, 271.2 mmol, for preparation see WO 0071129), phosphorus oxychloride (30.3 mL, 325.4 mmol) and diisopropylethyl amine (37.7 mL, 217 mmol) in toluene (800 mL) was heated to reflux under argon for 18 h and then cooled to room temperature. The mixture was concentrated on rotovap and the residue was diluted with dichloromethane (1000 mL) and cold sodium bicarbonate solution (300 mL). The resulting mixture was stirred at room temperature for 10 min. The separated organic layer was washed with cold brine (300 mL), dried, and concentrated in vacuo. The crude material was purified by chromatography on silica gel eluting with dichloromethane to provide the desired compound (64.8 g, 99%) as a yellow solid.

1. temperaturewas heated
2. temperatureto reflux under argon for 18 h
3. concentrationThe mixture was concentrated on rotovap
4. additionthe residue was diluted with dichloromethane (1000 mL) and cold sodium bicarbonate solution (300 mL)
5. washThe separated organic layer was washed with cold brine (300 mL)
6. customdried
7. concentrationconcentrated in vacuo
8. customThe crude material was purified by chromatography on silica gel eluting with dichloromethane

ORD record

ord-7bbaa21362d34d09a184058a2a3e39b0

Source dataset

uspto-grants-2005_08

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06933386B2