3,6-Dichloropyridazine → 6-((6-Chloro-[1,2,4]triazolo[4,3-b]pyridazin-3-yl)difluoromethyl)quinoline

HRID 40383

Reaction equation

HRID 40383 reaction equation
[F:1][C:2]([F:17])([C:7]1[CH:8]=[C:9]2[C:14](=[CH:15][CH:16]=1)[N:13]=[CH:12][CH:11]=[CH:10]2)[C:3]([NH:5][NH2:6])=O.[Cl:18][C:19]1[N:20]=[N:21][C:22](Cl)=[CH:23][CH:24]=1>Cl.CO>[Cl:18][C:19]1[CH:24]=[CH:23][C:22]2[N:5]([C:3]([C:2]([F:17])([F:1])[C:7]3[CH:8]=[C:9]4[C:14](=[CH:15][CH:16]=3)[N:13]=[CH:12][CH:11]=[CH:10]4)=[N:20][N:21]=2)[N:6]=1

Participants

5

Reactant 2

HCID 673313,6-DichloropyridazineHCID 589552502,2-Difluoro-2-(quinolin-6-yl)acetohydrazide

Product 1

HCID 576910336-((6-Chloro-[1,2,4]triazolo[4,3-b]pyridazin-3-yl)difluoromethyl)quinoline

Reagents, catalysts & solvents 2

HCID 313Hydrochloric AcidSolventHCID 887MethanolSolvent

Conditions

Temperature
90 °C

Procedure

A suspension of 2,2-difluoro-2-(quinolin-6-yl)acetohydrazide (2000 mg, 8432 μmol) and 3,6-dichloropyridazine (3768 mg, 25295 μmol) in 1.25 M HCl in MeOH (20 mL) was heated to 90° C. with microwaves for 50 min. The solvents were then removed under reduced pressure and residue partitioned between 9:1 CHCl3/IPA (60 mL) and 1 M NaOH (20 mL). The organic phase then dried over MgSO4, concentrated, then purified on silica (120 g) eluting with 1>2.5% of 2 M NH3 in MeOH/DCM to provide product isolated as a dark tan solid. MS (ESI pos. ion) m/z: 332 (MH+). Calc'd exact mass for C15H8ClF2N5: 331.

Workup

  1. customThe solvents were then removed under reduced pressure and residue
  2. custompartitioned between 9:1 CHCl3/IPA (60 mL) and 1 M NaOH (20 mL)
  3. dry with materialThe organic phase then dried over MgSO4
  4. concentrationconcentrated
  5. custompurified on silica (120 g)
  6. washeluting with 1>2.5% of 2 M NH3 in MeOH/DCM
  7. customto provide product
  8. customisolated as a dark tan solid

Sources & evidence

ORD record
ord-c84f7e07d9cb45bc9796ee6947f588a3
Source dataset
uspto-grants-2013_09
Patent number
US08524900B2

Linked notes

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