Acetone → 4-(4-(2,4-Difluorophenyl)-5-(3-isopropyl-[1,2,4]triazolo[4,3-b]pyridazin-6-yl)thiazol-2-yl)cyclohexanone

HRID 1930060Notes

Reaction equation

HRID 1930060 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.O1[C:29]2([CH2:34][CH2:33][CH:32]([C:35](=[S:37])[NH2:36])[CH2:31][CH2:30]2)[O:28]CC1.CC(C)=O.Cl>CN(C=O)C>[F:12][C:6]1[CH:7]=[C:8]([F:11])[CH:9]=[CH:10][C:5]=1[C:3]1[N:36]=[C:35]([CH:32]2[CH2:33][CH2:34][C:29](=[O:28])[CH2:30][CH2:31]2)[S:37][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

6

Reactant 4

HCID 180AcetoneHCID 313Hydrochloric AcidHCID 57929861HCID 57929861, compoundHCID 579299251,4-Dioxaspiro[4.5]decane-8-carbothioamide

Product 1

HCID 579298484-(4-(2,4-Difluorophenyl)-5-(3-isopropyl-[1,2,4]triazolo[4,3-b]pyridazin-6-yl)thiazol-2-yl)cyclohexanoneYield 69.5%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

The 2-bromo-1-(2,4-difluorophenyl)-2-(3-isopropyl-[1,2,4]triazolo[4,3-b]pyridazin-6-yl)ethanone (0.622 g, 1.57 mmol, Preparation #A.2) and 1,4-dioxaspiro[4.5]decane-8-carbothioamide (0.317 g, 1.57 mmol) were dissolved in DMF (5 mL) then stirred at ambient temperature for about 12 h. The mixture was concentrated under reduced pressure then acetone (25 mL) and concentrated hydrochloric acid (2 μL, 10 mmol) were added. The mixture was heated to about 60° C. for about 1.5 h then concentrated under reduced pressure, basified with 50% NaOH and diluted with water. The mixture was extracted with ethyl acetate then organic solution was dried over MgSO4, filtered and concentrated under reduced pressure. The material was purified by flash chromatography on silica gel using DCM/MeOH (95:5) as an eluent to give the title compound (0.495 g, 69%): LC/MS (Table 1, Method b) Rt=2.14 min; MS m/z: 454.2 (M+H)+.

Workup

  1. concentrationThe mixture was concentrated under reduced pressure
  2. temperatureThe mixture was heated to about 60° C. for about 1.5 h
  3. concentrationthen concentrated under reduced pressure
  4. additiondiluted with water
  5. extractionThe mixture was extracted with ethyl acetate
  6. dry with materialorganic solution was dried over MgSO4
  7. filtrationfiltered
  8. concentrationconcentrated under reduced pressure
  9. customThe material was purified by flash chromatography on silica gel

Sources & evidence

ORD record
ord-b55b774aeb904736b2fae18b64e78a13
Source dataset
uspto-grants-2012_05
Patent number
US08188083B2

Reaction notes

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