Hydrochloric Acid → Methyl 3-(6-(1-(2,6-dimethyl-4'-(trifluoromethyl)biphenyl-4-ylamino)-3-methylbutyl)nicotinamido)propanoate

温度

0 °C

Methyl 6-(1-(2,6-dimethyl-4′-(trifluoromethyl)biphenyl-4-ylamino)-3-methylbutyl)nicotinate (290 mg, 0.62 mmol) was dissolved in H2O (3 mL) and tetrahydrofuran (3 mL). The solution was cooled to 0° C. 1N LiOH (77.5 mg, 1.85 mmol) was added. The mixture was warmed to room temperature and stirred for 5 h. The mixture was then neutralized with 1N HCl and extracted with ethyl acetate. The organic layer was dried over sodium sulfate, filtered and concentrated. The residue was dissolved in N,N-dimethylformamide (5 mL). O-(7-azabenzotriazol-1-yl)-N,N,N′,N′-tetramethyluronium hexafluorophosphate (338 mg, 0.888 mmol) was added and the mixture was stirred for 45 minutes. Methyl 3-aminopropanoate hydrochloride (123 mg, 0.888 mmol) and diisopropylethylamine (306 mg, 2.37 mmol) were added. The resulting mixture was stirred overnight at room temperature. The mixture was diluted with saturated ammonium chloride and extracted with ethyl acetate. The organic layer was washed with water and brine, dried over sodium sulfate, filtered and concentrated to give methyl 3-(6-(1-(2,6-dimethyl-4′-(trifluoromethyl)biphenyl-4-ylamino)-3-methylbutyl)nicotinamido)propanoate. 1H NMR (400 MHz, CD3OD, δ): 8.88 (s, 1H), 8.10 (m, 1H), 7.64 (m, 3H), 7.23 (d, 2H), 6.31 (s, 2H), 4.55 (m, 1H), 3.65 (m, 5H), 2.65 (m, 2H), 1.82 (m, 6H), 1.60 (m, 1H), 1.0 (m, 6H).

1. temperatureThe mixture was warmed to room temperature
2. extractionextracted with ethyl acetate
3. dry with materialThe organic layer was dried over sodium sulfate
4. filtrationfiltered
5. concentrationconcentrated
6. dissolutionThe residue was dissolved in N,N-dimethylformamide (5 mL)
7. stirringthe mixture was stirred for 45 minutes
8. stirringThe resulting mixture was stirred overnight at room temperature
9. extractionextracted with ethyl acetate
10. washThe organic layer was washed with water and brine
11. dry with materialdried over sodium sulfate
12. filtrationfiltered
13. concentrationconcentrated

ORDレコード

ord-a8c504fdaa9c442fbf543659711c1618

出典データセット

uspto-grants-2014_08

DOI

10.6084/m9.figshare.5104873.v1

特許番号

US08809342B2