p-Toluenesulfonic acid → (S)-4-Amino-N-((3-fluoro-4-(trifluoromethoxy)phenyl)(3-fluoropyridin-2-yl)methyl)-5-hydroxypicolinamide

温度

180 °C

To a stirred solution of (S)-4-amino-N-((3-fluoro-4-(trifluoromethoxy)phenyl) (3-fluoropyridin-2-yl)methyl)-5-methoxypicolinamide (600 mg, 0.0013 mol) in NMP (10 mL) was added LiCl (168 mg, 0.0039 mol, Aldrich) followed by pTSA (754 mg, 0.0039 mol, Aldrich) at rt. The reaction mixture was stirred at 180° C. for 2 h. After completion of the reaction (monitored by TLC, 50% EtOAc in petroleum ether), the reaction mixture was cooled to room temperature and sat'd NaHCO3 (50 mL) was added and the aqueous solution was extracted with EtOAc (25 mL×2). The combined organic layers were washed with water (25 mL×2), saturated NaCl (25 mL) and dried over anhydrous sodium sulfate. The product thus obtained was purified by silica gel (60-120 mesh) column chromatography eluting with 60-70% EtOAc in petroleum ether to give the title compound as an off-white solid. 1H NMR (400 MHz, DMSO-d6) δ ppm 9.90 (s, 1H), 9.51 (d, J=8 Hz, 1H), 8.55 (d, J=4.8 Hz, 1H), 7.82-7.78 (m, 2H), 7.56-7.50 (m, 2H), 7.46 (d, J=1.6 Hz, 10.4 Hz, 1H), 7.30 (d, J=12.8, 2H), 6.48 (d, J=4.4 Hz, 1H), 5.78 (s, 2H). MS (ESI, positive ion) m/z: 441.3 (M+H).

1. temperaturethe reaction mixture was cooled to room temperature
2. extractionthe aqueous solution was extracted with EtOAc (25 mL×2)
3. washThe combined organic layers were washed with water (25 mL×2), saturated NaCl (25 mL)
4. dry with materialdried over anhydrous sodium sulfate
5. customThe product thus obtained
6. customwas purified by silica gel (60-120 mesh) column chromatography
7. washeluting with 60-70% EtOAc in petroleum ether

ORDレコード

ord-89606bf3a8814caaa1ba8972d222a4bb

出典データセット

uspto-grants-2015_08

DOI

10.6084/m9.figshare.5104873.v1

特許番号

US09096527B2