Trifluoroacetic acid → 2-((6-Chloro-3-(4-chloro-2-fluorobenzoyl)-2-methylimidazo[1,2-b]pyridazin-8-yl)methyl)isoindoline-1,3-dione

HRID 597857Notes

Reaction equation

HRID 597857 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.[CH:22]1[CH:27]=[C:26]2[C:28]([N:30]([CH2:33]C(O)=O)[C:31](=[O:32])[C:25]2=[CH:24][CH:23]=1)=[O:29].FC(F)(F)C(O)=O.S(OOS([O-])(=O)=O)([O-])(=O)=O.[NH4+].[NH4+]>O.[N+]([O-])([O-])=O.[Ag+].C(#N)C>[Cl:19][C:16]1[CH:17]=[C:18]([CH2:33][N:30]2[C:31](=[O:32])[C:25]3[C:26](=[CH:27][CH:22]=[CH:23][CH:24]=3)[C:28]2=[O:29])[C:13]2[N:14]([C:10]([C:8](=[O:9])[C:5]3[CH:6]=[CH:7][C:2]([Cl:1])=[CH:3][C:4]=3[F:21])=[C:11]([CH3:20])[N:12]=2)[N:15]=1

Participants

8

Reactant 4

HCID 6422Trifluoroacetic acidHCID 20825N-PhthaloylglycineHCID 62648Ammonium PersulfateHCID 56954583(4-Chloro-2-fluorophenyl)(6-chloro-2-methylimidazo[1,2-b]pyridazin-3-yl)methanone

Product 1

HCID 866424872-((6-Chloro-3-(4-chloro-2-fluorobenzoyl)-2-methylimidazo[1,2-b]pyridazin-8-yl)methyl)isoindoline-1,3-dione

Reagents, catalysts & solvents 3

HCID 24470Silver NitrateCatalystHCID 962WaterSolvent2×HCID 6342AcetonitrileSolvent

Conditions

Temperature
70 °C

Procedure

Combine (4-chloro-2-fluorophenyl)(6-chloro-2-methylimidazo[1,2-b]pyridazin-3-yl)methanone (5.6 g, 17.3 mmol), N-phthaloylglycine (6.0 g, 1.7 equiv.), acetonitrile (60 mL), water (15 mL), trifluoroacetic acid (0.26 mL, 0.2 equiv.), and silver nitrate (294 mg, 0.1 equiv.) in a round bottom flask with attached addition funnel and place under nitrogen. Heat to 70° C. and maintain at this temperature for 15 min. Dissolve ammonium persulfate (7.1 g, 1.8 equiv.) in water (15 mL) and charge to an addition funnel Add drop-wise to the reaction flask over approximately 20 min. Heat reaction at 70° C. for 1 h. A precipitate forms during this time; filter via Buchner funnel to isolate the title compound crude (7.3 g, 87%) as an off-white solid. LCMS (4 min)=483.0, 485.0, M+1).

Workup

  1. additionaddition funnel
  2. temperaturemaintain at this temperature for 15 min
  3. additionAdd
  4. temperatureHeat
  5. customreaction at 70° C. for 1 h
  6. filtrationfilter via Buchner funnel

Sources & evidence

ORD record
ord-8e1434153e3042648921261fd9edb84a
Source dataset
uspto-grants-2011_03
Patent number
US07897600B2

Reaction notes

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