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

HRID 1930051Notes

Reaction equation

HRID 1930051 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](=[S:27])[NH2:26]>C1COCC1>[F:12][C:6]1[CH:7]=[C:8]([F:11])[CH:9]=[CH:10][C:5]=1[C:3]1[N:26]=[CH:25][S:27][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 3005587MethanethioamideHCID 579298612-Bromo-1-(2,4-difluorophenyl)-2-(3-isopropyl-[1,2,4]triazolo[4,3-b]pyridazin-6-yl)ethanone

Product 1

HCID 579299484-(2,4-Difluorophenyl)-5-(3-isopropyl-[1,2,4]triazolo[4,3-b]pyridazin-6-yl)thiazoleYield 17.7%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

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 (0.60 g, 1.5 mmol, Preparation #A.2) in THF (25 mL) was added methanethioamide (0.19 g, 3.0 mmol, prepared according to Euro. J. Med. Chem., 2004, 39, 867-872). The reaction mixture was stirred at ambient temperature for about 15 h. The solvent was removed under reduced pressure. The crude material was purified by silica gel flash chromatography using DCM/MeOH (gradient, 100:0 to 95:10). This residue was then repurified by silica gel flash chromatography using DCM/ACN (gradient, 90:10 to 0:100). The residue was dissolved in Et2O and solvent removed under reduced pressure to give a yellow solid. The solid was dried overnight under high vacuum to afford the title compound (0.095 g, 17%) as a yellow solid: LC/MS (Table 1, Method a) Rt=2.39 min; MS m/z: 358.2 (M+H.

Workup

  1. customThe solvent was removed under reduced pressure
  2. customThe crude material was purified by silica gel flash chromatography
  3. customThis residue was then repurified by silica gel flash chromatography
  4. dissolutionThe residue was dissolved in Et2O
  5. customsolvent removed under reduced pressure
  6. customto give a yellow solid
  7. customThe solid was dried overnight under high vacuum

Sources & evidence

ORD record
ord-22bbaf0482254999bb89fc01c1049eee
Source dataset
uspto-grants-2012_05
Patent number
US08188083B2

Reaction notes

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