Реакция #1857590

Уравнение реакции

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

Выход 60.0%

Растворители

dichloromethane

DCM

Условия реакции

Обработка

1. 1
   workup.STIRRINGthe reaction was stirred for an additional 4 hours
2. 2
   Промывкаwashed with aqueous saturated NaHCO3 solution (5 mL, 2×)
3. 3
   ДругоеThe organic layer was collected
4. 4
   Другоеdried
5. 5
   Фильтрацияfiltered
6. 6
   ДругоеSolvents were removed under vacuum
7. 7
   Другоеpurified by reversed phase HPLC (5%-95% ACN in H2O: 25 minute gradient)
8. 8
   Концентрированиеconcentrated

Методика

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.

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