Water → 6-(6-(2,4-Difluorophenyl)-1-methyl-1H-imidazo[1,2-a]imidazol-5-yl)-3-isopropyl-[1,2,4]triazolo[4,3-b]pyridazine

HRID 1930008Notes

Reaction equation

HRID 1930008 reaction equation
[F:1][C:2]1[CH:7]=[C:6]([F:8])[CH:5]=[CH:4][C:3]=1[C:9]1[N:10]=[C:11]2[N:15]([C:16]=1[C:17]1[CH:18]=[CH:19][C:20]3[N:21]([C:23]([CH:26]([CH3:28])[CH3:27])=[N:24][N:25]=3)[N:22]=1)[CH:14]=[CH:13]O2.[CH3:29][NH2:30].O>O1CCOCC1>[F:1][C:2]1[CH:7]=[C:6]([F:8])[CH:5]=[CH:4][C:3]=1[C:9]1[N:10]=[C:11]2[N:30]([CH3:29])[CH:13]=[CH:14][N:15]2[C:16]=1[C:17]1[CH:18]=[CH:19][C:20]2[N:21]([C:23]([CH:26]([CH3:28])[CH3:27])=[N:24][N:25]=2)[N:22]=1

Participants

5

Reactant 3

HCID 962WaterHCID 6329MethylamineHCID 251346886-(2,4-Difluorophenyl)-5-(3-isopropyl-[1,2,4]triazolo[4,3-b]pyridazin-6-yl)imidazo[2,1-b]oxazole

Product 1

HCID 579299476-(6-(2,4-Difluorophenyl)-1-methyl-1H-imidazo[1,2-a]imidazol-5-yl)-3-isopropyl-[1,2,4]triazolo[4,3-b]pyridazineYield 56%

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent

Procedure

6-(2,4-Difluorophenyl)-5-(3-isopropyl-[1,2,4]triazolo[4,3-b]pyridazin-6-yl)imidazo[2,1-b]oxazole (0.200 g, 0.526 mmol, Example #8), 40% methylamine in water (1.50 mL, 15.4 mmol) and 1,4-dioxane (1 mL) were heated in a CEM® microwave at about 120° C. (250 psi maximum pressure, 10 min ramp, 300 max watts) for about 55 min. The mixture was concentrated under reduced pressure then treated with HOAc (1.5 mL). The solution was stirred at ambient temperature for about 1 h then the material was purified by RP-HPLC (Table 1, Method f). The desired fractions were collected and concentrated under reduced pressure to remove most of the ACN. The precipitate which formed was collected by filtration and washed with water (3 mL) then dried overnight under vacuum at about 70° C. to give the title compound (0.115 g, 56%): LC/MS (Table 1, Method g) Rt=1.88 min; MS m/z: 394.2 (M+H)+.

Workup

  1. concentrationThe mixture was concentrated under reduced pressure
  2. additionthen treated with HOAc (1.5 mL)
  3. customthe material was purified by RP-HPLC (Table 1, Method f)
  4. customThe desired fractions were collected
  5. concentrationconcentrated under reduced pressure
  6. customto remove most of the ACN
  7. customThe precipitate which formed
  8. filtrationwas collected by filtration
  9. washwashed with water (3 mL)
  10. customthen dried overnight under vacuum at about 70° C.

Sources & evidence

ORD record
ord-9d362dc1e75444bc9fb8094a13d0e040
Source dataset
uspto-grants-2012_05
Patent number
US08188083B2

Reaction notes

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