4-Propan-2-ylpiperazine-1-carbothioamide → 4-(2,4-Difluorophenyl)-5-(3-isopropyl-[1,2,4]triazolo[4,3-b]pyridazin-6-yl)-2-(4-isopropylpiperazin-1-yl)thiazole

HRID 1929992Notes

Reaction equation

HRID 1929992 reaction equation
Br[CH:2]([C:13]1[CH:14]=[CH:15][C:16]2[N:17]([C:19]([CH:22]([CH3:24])[CH3:23])=[N:20][N:21]=2)[N:18]=1)[C:3]([C:5]1[CH:10]=[CH:9][C:8]([F:11])=[CH:7][C:6]=1[F:12])=O.[CH:25]([N:28]1[CH2:33][CH2:32][N:31]([C:34](=[S:36])[NH2:35])[CH2:30][CH2:29]1)([CH3:27])[CH3:26]>CCO>[F:12][C:6]1[CH:7]=[C:8]([F:11])[CH:9]=[CH:10][C:5]=1[C:3]1[N:35]=[C:34]([N:31]2[CH2:32][CH2:33][N:28]([CH:25]([CH3:27])[CH3:26])[CH2:29][CH2:30]2)[S:36][C:2]=1[C:13]1[CH:14]=[CH:15][C:16]2[N:17]([C:19]([CH:22]([CH3:24])[CH3:23])=[N:20][N:21]=2)[N:18]=1

Participants

4

Reactant 2

HCID 47404374-Propan-2-ylpiperazine-1-carbothioamideHCID 579298612-Bromo-1-(2,4-difluorophenyl)-2-(3-isopropyl-[1,2,4]triazolo[4,3-b]pyridazin-6-yl)ethanone

Product 1

HCID 579298894-(2,4-Difluorophenyl)-5-(3-isopropyl-[1,2,4]triazolo[4,3-b]pyridazin-6-yl)-2-(4-isopropylpiperazin-1-yl)thiazoleYield 62.8%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Conditions

Temperature
40 °C

Procedure

To a solution of 2-bromo-1-(2,4-difluorophenyl)-2-(3-isopropyl-[1,2,4]triazolo[4,3-b]pyridazin-6-yl)ethanone (0.49 g, 1.24 mmol, Preparation #A.2) in EtOH (10 μL) was added 4-isopropylpiperazine-1-carbothioamide (0.21 g, 1.12 mmol, Preparation #AO.1.1). The reaction mixture was stirred at about 40° C. for about 2.5 h. The reaction mixture was cooled to ambient temperature and the solvent was removed under reduced pressure. DCM (35 mL) and water (20 mL) were added. The layers were partitioned and the organic layer was washed with additional water (200 mL). The organic layer was dried over MgSO4, filtered, and the solvent was removed under reduced pressure. The crude residue was purified by silica gel column chromatography DCM/MeOH (gradient from 100:0 to 90:10) to afford the title compound (0.34 g, 56%) as a yellow solid: LC/MS (Table 1, Method a) Rt=2.06 min; MS m/z: 484.2 (M+H)+.

Workup

  1. temperatureThe reaction mixture was cooled to ambient temperature
  2. customthe solvent was removed under reduced pressure
  3. additionDCM (35 mL) and water (20 mL) were added
  4. customThe layers were partitioned
  5. washthe organic layer was washed with additional water (200 mL)
  6. dry with materialThe organic layer was dried over MgSO4
  7. filtrationfiltered
  8. customthe solvent was removed under reduced pressure
  9. customThe crude residue was purified by silica gel column chromatography DCM/MeOH (gradient from 100:0 to 90:10)

Sources & evidence

ORD record
ord-80cd74e03ad94d36ba77889ed3ebedcd
Source dataset
uspto-grants-2012_05
Patent number
US08188083B2

Reaction notes

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