Dichloromethane → 1-(6-Chloroimidazo[1,2-b]pyridazin-3-yl)-1-(7-fluoroquinolin-6-yl)ethanol

HRID 69215Notes

Reaction equation

HRID 69215 reaction equation
[Cl:1][C:2]1[CH:3]=[CH:4][C:5]2[N:6]([C:8]([C:11]([C:13]3[CH:14]=[C:15]4[C:20](=[CH:21][C:22]=3[F:23])[N:19]=[CH:18][CH:17]=[CH:16]4)=[O:12])=[CH:9][N:10]=2)[N:7]=1.[CH3:24][Mg]Br.C(Cl)Cl.C([O-])(O)=O.[Na+]>C1COCC1.CCOCC>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]2[N:6]([C:8]([C:11]([C:13]3[CH:14]=[C:15]4[C:20](=[CH:21][C:22]=3[F:23])[N:19]=[CH:18][CH:17]=[CH:16]4)([OH:12])[CH3:24])=[CH:9][N:10]=2)[N:7]=1

Participants

7

Reactant 4

HCID 6344DichloromethaneHCID 516892Sodium BicarbonateHCID 58147533(6-Chloroimidazo[1,2-b]pyridazin-3-yl)(7-fluoroquinolin-6-yl)methanoneHCID 178418573HCID 178418573, compound2×

Product 1

HCID 581475421-(6-Chloroimidazo[1,2-b]pyridazin-3-yl)-1-(7-fluoroquinolin-6-yl)ethanol

Reagents, catalysts & solvents 2

HCID 3283Diethyl EtherSolvent2×HCID 8028TetrahydrofuranSolvent

Procedure

(6-Chloro-imidazo[1,2-b]pyridazin-3-yl)-(7-fluoro-quinolin-6-yl)-methanone (Stage 174.2, 294 mg, 0.9 mmol) was dissolved in anhydrous THF (70 mL) at 40° C. and methylmagnesium bromide in Et2O (3 M, 0.36 mL) was slowly added and the RM was then allowed to cool down to rt and stirred for 2 h. More methylmagnesium bromide in Et2O (3 M, 0.5 mL) was added and the RM was stirred for 1 h more. It was then taken into DCM and 10% aqueous NaHCO3 solution and extracted. The organic phase was dried on MgSO4. After evaporation of the solvent the crude was purified by flash chromatography (CombiFlash® Companion System®, with RediSep® silica gel column, EtOAc/MeOH=100:0->90:10) to afford the title compound (tR 3.74 min (conditions 3), MH+=343, 1H-NMR in DMSO-d6: 8.87 (dd, 1H); 8.50 (d, 1H); 8.49 (d, 1H); 8.18 (d, 1H); 7.85 (s, 1H); 7.59 (d, 1H); 7.51 (dd, 1H); 7.23 (d, 1H); 6.33 (s, 1H); 2.13 (s, 3H))

Workup

  1. stirringthe RM was stirred for 1 h more
  2. extractionextracted
  3. customThe organic phase was dried on MgSO4
  4. customAfter evaporation of the solvent the crude
  5. customwas purified by flash chromatography (CombiFlash® Companion System®, with RediSep® silica gel column, EtOAc/MeOH=100:0->90:10)

Sources & evidence

ORD record
ord-2290480dc8bc4d5a819fb5ed3a807c1d
Source dataset
uspto-grants-2014_09
Patent number
US08822468B2

Reaction notes

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