Oxalyl chloride → (2E)-3-{3-cyano-4,6-dimethyl-1-[(1S)-1,2,3,4-tetrahydronaphthalen-1-yl]-1H-pyrrolo[2,3-b]pyridin-2-yl}-N-(4-hydroxy-3-methoxybenzyl)prop-2-enamide

To a solution of (2E)-3-{3-cyano-4,6-dimethyl-1-[(1S)-1,2,3,4-tetrahydronaphthalen-1-yl]-1H-pyrrolo[2,3-b]pyridin-2-yl}prop-2-enoic acid (300 mg, 0.808 mmol) in THF (3 ml) were added DMF (0.03 ml) and oxalylchloride (0.0846 ml, 0.970 mmol), the mixture was stirred at room temperature for 1 hour and the solvent was distilled off under reduced pressure. The residue was added under ice-cooling to a solution of 4-hydroxy-3-methoxybenzylamine hydrochloride (183 mg, 0.968 mmol), diisopropylethylamine (0.737 ml, 4.24 mmol) and THF (2 ml), and the mixture was stirred under ice-cooling for 2 hours and at room temperature for 12 hours. The reaction solution was poured into water and extracted with ethyl acetate. The extract was washed with water and dried over anhydrous magnesium sulfate, and the solvent was distilled off under reduced pressure. The residue was purified by silica gel column chromatography (hexane:ethyl acetate=1:1) to give the objective product as a solid material.

1. distillationthe solvent was distilled off under reduced pressure
2. additionThe residue was added under ice-
3. stirringthe mixture was stirred under ice-
4. temperaturecooling for 2 hours and at room temperature for 12 hours
5. extractionextracted with ethyl acetate
6. washThe extract was washed with water
7. dry with materialdried over anhydrous magnesium sulfate
8. distillationthe solvent was distilled off under reduced pressure
9. customThe residue was purified by silica gel column chromatography (hexane:ethyl acetate=1:1)

ORDレコード

ord-a91bdb7b6cea485091762aa8da8d41b3

出典データセット

uspto-grants-2009_09

DOI

10.6084/m9.figshare.5104873.v1

特許番号

US07582651B2