Potassium Iodide → N-(6-([1,2,4]triazolo[4,3-a]pyridin-3-ylthio)imidazo[1,2-b]pyridazin-2-yl)cyclopropanecarboxamide

Temperature

120 °C

A mixture of 6-([1,2,4]triazolo[4,3-a]pyridin-3-ylthio)pyridazin-3-amine (2.443 g, 10 mmol), N-(2-bromoacetyl)cyclopropanecarboxamide (3.09 g, 15.00 mmol), potassium hydrogenphosphate (5.23 g, 30.0 mmol) and potassium iodide (0.830 g, 5.00 mmol) in DMA (100 mL) was stirred at 120° C. for 2 hrs. Additional amounts of N-(2-bromoacetyl)cyclopropanecarboxamide (2.06 g, 10 mmol) and potassium hydrogenphosphate (1.74 g, 10 mmol) were added to the mixture and the reaction was stirred at 120° C. for another 2 hrs. The reaction was then stirred at room temperature overnight. The reaction mixture was again stirred at 140° C. for 3 hrs and then cooled to room temperature. The resulting solid was filtered off and rinsed with DMA. The filtrate was concentrated to 100 mL and then poured into water (300 mL). The resulting precipitate was collected by filtration and rinsed thoroughly with water. The solid material was re-suspended in 10% MeOH/CH2Cl2 (100 mL), sonicated, refluxed for 30 min and cooled to room temperature. The MeOH/CH2Cl2 solution was filtered through a silica plug, rinsed with 10% MeOH/CH2Cl2 (200 mL). To above organic solution, activated charcoal (0.5 g) was added, the solution was refluxed for 30 min, and then stirred at room temperature overnight. The charcoal was filtered through Celite, and the filtrate was concentrated to dryness to provide an off white solid. This solid was refluxed in MeOH (10 mL) for 30 min. and cooled to room temperature. The resulting off white solid was collected by filtration, rinsed with MeOH (2 mL) and dried in vacuum to provide the title compound, N-(6-([1,2,4]Triazolo[4,3-a]pyridin-3-ylthio)imidazo[1,2-b]pyridazin-2-yl)cyclopropanecarboxamide (1.2 g). 1H NMR (400 MHz, DMSO-d6) δ=11.17 (s, 1 H), 8.57-8.44 (m, 1 H), 8.03-7.94 (m, 1 H), 7.96-7.88 (m, 2 H), 7.59 (ddd, J=1.0, 6.6, 9.3 Hz, 1 H), 7.22-7.11 (m, 1 H), 7.11-7.03 (m, 1 H), 1.97-1.84 (m, 1 H), 0.83-0.73 (m, 4 H) ESI-MS:m/z 352.3 (M+H)+. MP 193-195° C.

1. stirringthe reaction was stirred at 120° C. for another 2 hrs
2. stirringThe reaction was then stirred at room temperature overnight
3. stirringThe reaction mixture was again stirred at 140° C. for 3 hrs
4. temperaturecooled to room temperature
5. filtrationThe resulting solid was filtered off
6. washrinsed with DMA
7. concentrationThe filtrate was concentrated to 100 mL
8. additionpoured into water (300 mL)
9. filtrationThe resulting precipitate was collected by filtration
10. washrinsed thoroughly with water
11. customsonicated
12. temperaturerefluxed for 30 min
13. temperaturecooled to room temperature
14. filtrationThe MeOH/CH2Cl2 solution was filtered through a silica plug
15. washrinsed with 10% MeOH/CH2Cl2 (200 mL)
16. additionwas added
17. temperaturethe solution was refluxed for 30 min
18. stirringstirred at room temperature overnight
19. filtrationThe charcoal was filtered through Celite
20. concentrationthe filtrate was concentrated to dryness
21. customto provide an off white solid
22. temperaturecooled to room temperature
23. filtrationThe resulting off white solid was collected by filtration
24. washrinsed with MeOH (2 mL)
25. customdried in vacuum

ORD record

ord-aeb9d7d84dc242ca9913b7e577caca67

Source dataset

uspto-grants-2012_05

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08178534B2