Acetic Acid → 6-Bromo-3-(6-chloro-3-pyridinyl)-5-fluoro-1H-indazole

HRID 2353391Notes

Reaction equation

HRID 2353391 reaction equation
[Br:1][C:2]1[C:7]([F:8])=[CH:6][C:5]([C:9]([C:11]2[CH:12]=[N:13][C:14]([Cl:17])=[CH:15][CH:16]=2)=O)=[C:4](F)[CH:3]=1.[NH:19](C(OC(C)(C)C)=O)[NH2:20].C(O)(=O)C>CO>[Br:1][C:2]1[CH:3]=[C:4]2[C:5]([C:9]([C:11]3[CH:12]=[N:13][C:14]([Cl:17])=[CH:15][CH:16]=3)=[N:19][NH:20]2)=[CH:6][C:7]=1[F:8]

Participants

5

Reactant 3

HCID 176Acetic AcidHCID 70091tert-Butyl carbazateHCID 58830637HCID 58830637, compound

Product 1

HCID 588306386-Bromo-3-(6-chloro-3-pyridinyl)-5-fluoro-1H-indazoleYield 23.2%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Conditions

Temperature
150 °C

Procedure

Impure (4-bromo-2,5-difluorophenyl)(6-chloro-3-pyridinyl)methanone (0.548 g) in methanol (2 ml) was stirred with 1,1-dimethylethyl hydrazinecarboxylate (0.152 g) and acetic acid (100 μl) for 20 h. The crude mixture was partitioned between sodium bicarbonate and chloroform. The organic layer was separated using a hydrophobic filter tube and the solvent was removed under vacuum. The crude material in THF (1 ml) was treated with DBU (0.358 ml) and heated in a sealed tube in a microwave oven at 150° C. for 30 min. The reaction mixture was cooled and partitioned between ethyl acetate and 0.5M aqueous hydrochloric acid. The organic layer was washed with water then brine then separated using a hydrophobic filter tube. The organic phase was concentrated under vacuum and the residue was purifiedon a silica SPE cartridge (50 g) eluting with cyclohexane/ethyl acetate (100:0 to 0:100) to give the title compound (87 mg).

Workup

  1. customThe crude mixture was partitioned between sodium bicarbonate and chloroform
  2. customThe organic layer was separated
  3. customthe solvent was removed under vacuum
  4. additionThe crude material in THF (1 ml) was treated with DBU (0.358 ml)
  5. temperatureThe reaction mixture was cooled
  6. custompartitioned between ethyl acetate and 0.5M aqueous hydrochloric acid
  7. washThe organic layer was washed with water
  8. custombrine then separated
  9. concentrationThe organic phase was concentrated under vacuum
  10. washeluting with cyclohexane/ethyl acetate (100:0 to 0:100)

Sources & evidence

ORD record
ord-2e47da82da094d268be665817bcf5191
Source dataset
uspto-grants-2010_07
Patent number
US07750026B2

Reaction notes

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