Reacción #1857590

Ecuación de reacción

triethylamine

1-((3,5-dimethylisoxazol-4-yl)methyl)-1H-pyrazol-4-amine hydrochloride

picolinic acid

HOBt

EDC

→

N-(1-((3,5-dimethylisoxazol-4-yl)methyl)-1H-pyrazol-4-yl)picolinamide

Rendimiento 60.0%

Disolventes

dichloromethane

DCM

Condiciones de reacción

Tratamiento posterior

1. 1
   workup.STIRRINGthe reaction was stirred for an additional 4 hours
2. 2
   Lavadowashed with aqueous saturated NaHCO3 solution (5 mL, 2×)
3. 3
   OtroThe organic layer was collected
4. 4
   Otrodried
5. 5
   Filtraciónfiltered
6. 6
   OtroSolvents were removed under vacuum
7. 7
   Otropurified by reversed phase HPLC (5%-95% ACN in H2O: 25 minute gradient)
8. 8
   Concentraciónconcentrated

Procedimiento

1-((3,5-dimethylisoxazol-4-yl)methyl)-1H-pyrazol-4-amine hydrochloride (example 4-1a) (400 mg, 2.1 mmol), picolinic acid (256 mg, 2.1 mmol), and HOBt (388 mg, 2.50 mmol) were mixed in DCM (7 mL). The reaction was treated with triethylamine (670 mL, 4.8 mmol) and stirred for 15 minutes at room temperature under a nitrogen atmosphere. EDC (598 mg, 3.1 mmol) was added and the reaction was stirred for an additional 4 hours. The reaction was then diluted with dichloromethane (5 mL) and washed with aqueous saturated NaHCO3 solution (5 mL, 2×) and then with aqueous saturated NaCl solution (5 mL). The organic layer was collected, dried, and filtered. Solvents were removed under vacuum. The crude product was re-suspended in EtOH (5 mL) and purified by reversed phase HPLC (5%-95% ACN in H2O: 25 minute gradient). The pure fractions were combined and concentrated to afford N-(1-((3,5-dimethylisoxazol-4-yl)methyl)-1H-pyrazol-4-yl)picolinamide (372 mg, 60%) as a white solid. 1H NMR (CDCl3, 400 MHz): δ 2.21 (s, 3H), 2.44 (s, 3H), 5.05 (s, 2H), 7.49-7.47 (m, 1H), 7.59 (s, 1H), 7.93-7.88 (dt, J=14, 2 Hz, 1H), 8.07 (s, 1H), 8.24-8.21 (d, J=8 Hz, 1H), 8.61-8.56 (m, 1H), 9.83 (bs, 1H). LC/MS; [M+H] calculated for C15H15N5O2; expected 297.1. Found 298.3. Melting point: 135-137° C.

Fuente