Chloro-N,N,N',N'-tetramethylformamidinium Hexafluorophosphate → 6-iodo-N,N-dimethyl-[1,2,4]triazolo[4,3-b]pyridazin-3-amine

The 3-hydrazinyl-6-iodopyridazine (1.00 g, 4.24 mmol, prepared using General Procedure D from Example #9, Step A with hydrazine) was dissolved in DMF (10 mL) then N-(chloro(dimethylamino)methylene)-N-methylmethanaminium hexafluorophosphate(V) (1.31 g, 4.66 mmol, Fluka) was added. The solution was stirred for about 5 min and then TEA (1.30 mL, 9.32 mmol) was added. The mixture was stirred at ambient temperature for about 1 h then at about 60° C. for about 2 h. The reaction was concentrated under reduced pressure then the mixture was partitioned between DCM (20 mL) and saturated aqueous NaHCO3. The layers were separated then the organic solution was dried over MgSO4, filtered and concentrated under reduced pressure. The material was purified by flash chromatography on silica gel with DCM/MeOH (95:5) as an eluent. The fractions were collected then concentrated under reduced pressure and the residue was triturated with Et2O (20 mL). The solid was collected by filtration and dried overnight under vacuum to give the title compound (1.01 g, 90%): LC/MS (Table 1, Method g) Rt=1.60 min; MS m/z: 289.8 (M+H)+.

1. stirringThe mixture was stirred at ambient temperature for about 1 h
2. waitat about 60° C. for about 2 h
3. concentrationThe reaction was concentrated under reduced pressure
4. customthe mixture was partitioned between DCM (20 mL) and saturated aqueous NaHCO3
5. customThe layers were separated
6. dry with materialthe organic solution was dried over MgSO4
7. filtrationfiltered
8. concentrationconcentrated under reduced pressure
9. customThe material was purified by flash chromatography on silica gel with DCM/MeOH (95:5) as an eluent
10. customThe fractions were collected
11. concentrationthen concentrated under reduced pressure
12. customthe residue was triturated with Et2O (20 mL)
13. filtrationThe solid was collected by filtration
14. customdried overnight under vacuum

ORD record

ord-466964be0eff4ae9a2ac3483b6f0f497

Source dataset

uspto-grants-2012_05

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08188083B2