Methyl morpholine oxide → (4-Chloro-2-fluorophenyl)(6-chloro-2-methyl-8-(morpholinomethyl)imidazo[1,2-b]pyridazin-3-yl)methanone

HRID 597868Notes

Reaction equation

HRID 597868 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]([C:10]2[N:14]3[N:15]=[C:16]([Cl:19])[CH:17]=[CH:18][C:13]3=[N:12][C:11]=2[CH3:20])=[O:9])=[C:4]([F:21])[CH:3]=1.[CH3:22][N+:23]1([O-])[CH2:28][CH2:27][O:26][CH2:25][CH2:24]1>CC(CC(C)=O)=O.CC(CC(C)=O)=O.O=[V].C(O)C>[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]([C:10]2[N:14]3[N:15]=[C:16]([Cl:19])[CH:17]=[C:18]([CH2:22][N:23]4[CH2:28][CH2:27][O:26][CH2:25][CH2:24]4)[C:13]3=[N:12][C:11]=2[CH3:20])=[O:9])=[C:4]([F:21])[CH:3]=1

Participants

5

Reactant 2

HCID 82029Methyl morpholine oxideHCID 56954583(4-Chloro-2-fluorophenyl)(6-chloro-2-methylimidazo[1,2-b]pyridazin-3-yl)methanone

Product 1

HCID 56954584(4-Chloro-2-fluorophenyl)(6-chloro-2-methyl-8-(morpholinomethyl)imidazo[1,2-b]pyridazin-3-yl)methanone

Reagents, catalysts & solvents 2

HCID 407389Vanadium oxyacetoacetonateCatalystHCID 702EthanolSolvent2×

Procedure

Add ethanol (12 L), (4-chloro-2-fluorophenyl)(6-chloro-2-methylimidazo[1,2-b]pyridazin-3-yl)methanone (897.70 g, 2.77 mol) and bis(2,4-pentanedionato)oxovanadium (IV) (146.81 g, 553.67 mmol) to a reaction vessel with a nitrogen atmosphere. Add an ethanol (6 L) solution of 4-methylmorpholine 4-oxide (3.89 kg, 33.21 mol) drop-wise over 150 min keeping the reaction temperature at 23-33° C.; then heat the reaction at 40° C. for 48 h. Cool the reaction and concentrate by removal of solvent (13 L). Filter the resulting mixture, rinse the filter cake with hexane (1 L) and then dry. (728 g, 66.25%; mp 145-147° C.; M+=423).

Workup

  1. customat 23-33° C.
  2. temperaturethen heat
  3. customthe reaction at 40° C. for 48 h
  4. temperatureCool
  5. customthe reaction
  6. concentrationconcentrate by removal of solvent (13 L)
  7. filtrationFilter the resulting mixture
  8. washrinse the filter cake with hexane (1 L)
  9. customdry

Sources & evidence

ORD record
ord-d29f2af9e9ac4fc9a8153462fdecc538
Source dataset
uspto-grants-2011_03
Patent number
US07897600B2

Reaction notes

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