1-(6-Chloroimidazo(1,2-b)pyridazin-3-yl)ethan-1-one → 1-(6-Chloro-imidazo[1,2-b]pyridazin-3-yl)-1-(4,6-difluoro-1-methyl-1H-indazol-5-yl)-ethanol

HRID 1942061Notes

Reaction equation

HRID 1942061 reaction equation
[F:1][C:2]1[CH:10]=[C:9]([F:11])[CH:8]=[C:7]2[C:3]=1[CH:4]=[N:5][N:6]2[CH3:12].[Cl:13][C:14]1[CH:15]=[CH:16][C:17]2[N:18]([C:20]([C:23](=[O:25])[CH3:24])=[CH:21][N:22]=2)[N:19]=1>C1COCC1>[Cl:13][C:14]1[CH:15]=[CH:16][C:17]2[N:18]([C:20]([C:23]([C:10]3[C:2]([F:1])=[C:3]4[C:7](=[CH:8][C:9]=3[F:11])[N:6]([CH3:12])[N:5]=[CH:4]4)([OH:25])[CH3:24])=[CH:21][N:22]=2)[N:19]=1

Participants

4

Reactant 2

HCID 132488051-(6-Chloroimidazo(1,2-b)pyridazin-3-yl)ethan-1-oneHCID 579174794,6-Difluoro-1-methyl-1H-indazole

Product 1

HCID 581475291-(6-Chloro-imidazo[1,2-b]pyridazin-3-yl)-1-(4,6-difluoro-1-methyl-1H-indazol-5-yl)-ethanol

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

N-BuLi, 6.88 mL, was added dropwise to a solution of 4,6-difluoro-1-methyl-1H-indazole ((xvi), 1.68 g, 10 mmol) in dry THF (50 mL) at −78° C. The solution was stirred at this temperature for 1 h, and then the solution of 1-(6-chloro-imidazo[1,2-b]pyridazin-3-yl)ethanone (CAS 90734-71-7, 1.95 g, 10 mmol) in 50 mL THF was added dropwise at −70/75° C. After stirring additional 3 h at −70/75° C. the RM was quenched with NH4C110%, and at 0° C. diluted with water, and extracted with EtOAc (3×). The organic layers were washed with brine, dried over Na2SO4, filtered and concentrated. The residue was purified by flash chromatography to afford the title compound as a yellow foam (tR 4.40 min (conditions 5), MH+=364.2, 1H-NMR in DMSO-d6: 8.16 (d, 1H); 8.11 (s, 1H); 7.85 (s, 1H); 7.30 (d, 1H); 7.22 (d, 1H); 6.26 (s, 1H); 3.96 (s, 3H); 2.12 (d, 3H)).

Workup

  1. stirringAfter stirring additional 3 h at −70/75° C. the RM
  2. customwas quenched with NH4C110%
  3. additionat 0° C. diluted with water
  4. extractionextracted with EtOAc (3×)
  5. washThe organic layers were washed with brine
  6. dry with materialdried over Na2SO4
  7. filtrationfiltered
  8. concentrationconcentrated
  9. customThe residue was purified by flash chromatography

Sources & evidence

ORD record
ord-1a3b647a4805497092892d89d754edfc
Source dataset
uspto-grants-2013_03
Patent number
US08389526B2

Reaction notes

Loading…