반응 #49052

반응 방정식

Methyl 5-amino-pentanoate hydrochloride

sodium cyanoborohydride

3,4-difluoro-2-(2-fluoro-4-iodo-phenylamino)-5-formyl-N-(2-hydroxy-ethoxy)-benzamide

→

3,4-difluoro-2-(2-fluoro-4-iodo-phenylamino)-N-(2-hydroxy-ethoxy)-5-(2-oxo-piperidin-1-ylmethyl)-benzamide

수율 37.0%

용매

tetrahydrofuran

반응 조건

후처리

1. 1
   기타Then, the reaction vessel was equipped with a reflux condenser
2. 2
   온도the mixture was heated at 60° C. for 2 days
3. 3
   기타After completion of the reaction
4. 4
   추출the reaction mixture was extracted with ethyl acetate
5. 5
   세척the organic layer was washed sequentially with water and saturated brine
6. 6
   건조dried over anhydrous sodium sulfate
7. 7
   농축concentrated under reduced pressure
8. 8
   기타The resultant residue was purified by silica gel flash chromatography (Mega Bond Elut, Varian, 4% methanol/methylene chloride as an eluent)

실험 절차

Methyl 5-amino-pentanoate hydrochloride {see J. Org. Chem. (1968) 1581} (128 mg, 0.178 mmol) and sodium cyanoborohydride (45 mg, 0.718 mmol) were added to a solution of 3,4-difluoro-2-(2-fluoro-4-iodo-phenylamino)-5-formyl-N-(2-hydroxy-ethoxy)-benzamide (115 mg, 0.239 mmol) obtained in Step F of Example 1 in tetrahydrofuran (anhydrous, 4.0 mL). The mixture was stirred at room temperature for 1.5 hours. Then, the reaction vessel was equipped with a reflux condenser, and the mixture was heated at 60° C. for 2 days. After completion of the reaction, the reaction mixture was extracted with ethyl acetate, and the organic layer was washed sequentially with water and saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The resultant residue was purified by silica gel flash chromatography (Mega Bond Elut, Varian, 4% methanol/methylene chloride as an eluent) to give 3,4-difluoro-2-(2-fluoro-4-iodo-phenylamino)-N-(2-hydroxy-ethoxy)-5-(2-oxo-piperidin-1-ylmethyl)-benzamide (Compound H-4, 42.7 mg, 37%) as a white solid.

출처