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

HRID 1929991Notes

Reaction equation

HRID 1929991 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.[N:25]1([C:31](=[S:33])[NH2:32])[CH2:30][CH2:29][CH2:28][CH2:27][CH2:26]1>CCO>[F:12][C:6]1[CH:7]=[C:8]([F:11])[CH:9]=[CH:10][C:5]=1[C:3]1[N:32]=[C:31]([N:25]2[CH2:30][CH2:29][CH2:28][CH2:27][CH2:26]2)[S:33][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 1551232Piperidine-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 579299704-(2,4-Difluorophenyl)-5-(3-isopropyl-[1,2,4]triazolo[4,3-b]pyridazin-6-yl)-2-(piperidin-1-yl)thiazoleYield 39%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

A mixture of 2-bromo-1-(2,4-difluorophenyl)-2-(3-isopropyl-[1,2,4]triazolo[4,3-b]pyridazin-6-yl)ethanone (0.250 g, 0.632 mmol; Preparation #A.2) and piperidine-1-carbothioamide (Oakwood Products Inc., 0.082 g, 0.57 mmol) in EtOH (3 mL) was heated to reflux for about 3 h. After cooling to ambient temperature, the crude mixture was partitioned between DCM and water. The organics were dried over MgSO4, filtered, concentrated under reduced pressure, and purified by silica gel chromatography using heptane/EtOAc (linear gradient, 50:50 to 0:100) to give the title compound (0.098 g, 35%): LC/MS (Table 1, Method a) Rt=4.18 min; MS m/z: 441.8 (M+H)+.

Workup

  1. temperaturewas heated
  2. temperatureto reflux for about 3 h
  3. customthe crude mixture was partitioned between DCM and water
  4. dry with materialThe organics were dried over MgSO4
  5. filtrationfiltered
  6. concentrationconcentrated under reduced pressure
  7. custompurified by silica gel chromatography

Sources & evidence

ORD record
ord-92d717cd8b5c411da3d75d88fc15cb9d
Source dataset
uspto-grants-2012_05
Patent number
US08188083B2

Reaction notes

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