Trifluoroacetic acid → 4-((6-Chloro-3-(4-chloro-2-fluorobenzyl)-2-methylimidazo[1,2-b]pyridazin-8-yl)methyl)morpholine hydrochloride

HRID 597869Notes

Reaction equation

HRID 597869 reaction equation
C([SiH](CC)CC)C.[Cl:8][C:9]1[CH:14]=[CH:13][C:12]([C:15]([C:17]2[N:21]3[N:22]=[C:23]([Cl:33])[CH:24]=[C:25]([CH2:26][N:27]4[CH2:32][CH2:31][O:30][CH2:29][CH2:28]4)[C:20]3=[N:19][C:18]=2[CH3:34])=O)=[C:11]([F:35])[CH:10]=1.FC(F)(F)C(O)=O>>[ClH:8].[Cl:33][C:23]1[CH:24]=[C:25]([CH2:26][N:27]2[CH2:28][CH2:29][O:30][CH2:31][CH2:32]2)[C:20]2[N:21]([C:17]([CH2:15][C:12]3[CH:13]=[CH:14][C:9]([Cl:8])=[CH:10][C:11]=3[F:35])=[C:18]([CH3:34])[N:19]=2)[N:22]=1

Participants

4

Reactant 3

HCID 6422Trifluoroacetic acidHCID 12052TriethylsilaneHCID 56954584(4-Chloro-2-fluorophenyl)(6-chloro-2-methyl-8-(morpholinomethyl)imidazo[1,2-b]pyridazin-3-yl)methanone

Product 1

HCID 866424894-((6-Chloro-3-(4-chloro-2-fluorobenzyl)-2-methylimidazo[1,2-b]pyridazin-8-yl)methyl)morpholine hydrochloride

Procedure

At 26° C., combine triethylsilane (110 g, 946 mmol) and (4-chloro-2-fluorophenyl)(6-chloro-2-methyl-8-(morpholinomethyl)imidazo[1,2-b]pyridazin-3-yl)methanone (50.1 g, 117.06 mmol) to form a solution. Add trifluoro acetic acid (150 mL, 1.98 mol) to the reaction mixture then heat at 78° C. for 24 h. Cool the reaction to ambient temperature and separate the mixture to remove the top layer. Dissolve the bottom layer with ethyl acetate (1 L) and adjust the pH to 11 with sodium hydroxide (4 N, 500 mL). Separate the organic layer and add HCl (4 M in ethyl ether) to the organic layer to form the HCl salt. Filter and dry the HCl salt. (100 g (96%); mp=237-238° C.; M+=409).

Workup

  1. customAt 26° C.
  2. customto form a solution
  3. temperatureCool
  4. customthe reaction to ambient temperature
  5. customseparate the mixture
  6. customto remove the top layer
  7. dissolutionDissolve the bottom layer with ethyl acetate (1 L)
  8. customSeparate the organic layer
  9. additionadd HCl (4 M in ethyl ether) to the organic layer

Sources & evidence

ORD record
ord-5f71b3eae12e4c87bec3daa713ffe630
Source dataset
uspto-grants-2011_03
Patent number
US07897600B2

Reaction notes

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