N,2-Dimethoxy-N-methylpyridine-4-carboxamide → HCID 46183761, compound

Temperature

0 °C

(2-Methoxypyridin-4-yl)(2-(4-(trifluoromethyl)phenylamino)-[1,2,4]triazolo[1,5-a]pyridin-5-yl)methanone. A stirred mixture of 5-bromo-N-(4-(trifluoromethyl)phenyl)-[1,2,4]triazolo[1,5-c]pyridin-2-amine (1.53 g, 4.28 mmol) in tetrahydrofuran (35 mL) was heated briefly with a heat gun under nitrogen until all solids dissolved. The resulting clear red solution was cooled with a dry ice acetone bath under nitrogen. n-Butyllithium (5.76 mL, 9.21 mmol, 1.6 M in hexane) was added dropwise slowly via syringe. During the addition the reaction became black-colored. After 40 min N,2-dimethoxy-N-methylisonicotinamide (4.61 mL, 9.21 mmol, 2 M in tetrahydrofuran) was added. The cold bath was removed and the resulting mixture was warmed to 0° C. over 15 min. After 30 min at 0° C., water (20 mL) was added and the resulting mixture was stirred vigorously at room temperature for 15 min. The resulting mixture was diluted with ethyl acetate and shaken in a separatory funnel. The layers were separated and the organics were washed with brine, dried over magnesium sulfate, filtered, and concentrated on a rotary evaporator. The residue was dissolved in hot ethyl acetate and purified using flash chromatography (Biotage) (10-100% ethyl acetate in hexane). Fractions containing the desired product were combined and concentrated on a rotary evaporator down to ˜10 mL of ethyl acetate. Hexane (10 mL) was added. Solids were collected by vacuum filtration, washed with hexane, and dried under high vacuum to give the desired product (0.864 g, 2.090 mmol, 49% yield) as a yellow solid. 1H NMR (400 MHz, DMSO-d6) δ (ppm) 10.23 (s, 1H), 8.43 (d, J=5.47 Hz, 1H), 7.93 (dd, J=0.98, 8.79 Hz, 1H), 7.77 (dd, J=7.42, 8.98 Hz, 1H), 7.53-7.60 (m, 2H), 7.45-7.53 (m, 3H), 7.31 (dd, J=1.37, 5.27 Hz, 1H), 7.16 (s, 1H), 3.91 (s, 3H); 19F NMR (376 MHz, DMSO-d6) δ (ppm)-60.23 (s, 3F); MS (ESI) m/z 414.2 [M+1]+.

1. temperaturewas heated briefly with a heat gun under nitrogen until all solids
2. dissolutiondissolved
3. temperatureThe resulting clear red solution was cooled with a dry ice acetone bath under nitrogen
4. additionDuring the addition the reaction
5. customThe cold bath was removed
6. additionwater (20 mL) was added
7. additionThe resulting mixture was diluted with ethyl acetate
8. stirringshaken in a separatory funnel
9. customThe layers were separated
10. washthe organics were washed with brine
11. dry with materialdried over magnesium sulfate
12. filtrationfiltered
13. concentrationconcentrated on a rotary evaporator
14. dissolutionThe residue was dissolved in hot ethyl acetate
15. custompurified
16. additionFractions containing the desired product
17. concentrationconcentrated on a rotary evaporator down to ˜10 mL of ethyl acetate
18. additionHexane (10 mL) was added
19. filtrationSolids were collected by vacuum filtration
20. washwashed with hexane
21. customdried under high vacuum

ORD record

ord-6cbf9c09326545648446d7f2729ecff8

Source dataset

uspto-grants-2012_10

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08299056B2