Bromine → 3-Bromo-6-(6-methyl-[1,2,4]triazolo[4,3-b]pyridazin-3-ylsulfanyl)-quinoline

HRID 1890957Notes

Reaction equation

HRID 1890957 reaction equation
[CH3:1][C:2]1[CH:3]=[CH:4][C:5]2[N:6]([C:8]([S:11][C:12]3[CH:13]=[C:14]4[C:19](=[CH:20][CH:21]=3)[N:18]=[CH:17][CH:16]=[CH:15]4)=[N:9][N:10]=2)[N:7]=1.[Br:22]Br>C(O)(=O)C>[Br:22][C:16]1[CH:17]=[N:18][C:19]2[C:14]([CH:15]=1)=[CH:13][C:12]([S:11][C:8]1[N:6]3[N:7]=[C:2]([CH3:1])[CH:3]=[CH:4][C:5]3=[N:10][N:9]=1)=[CH:21][CH:20]=2

Participants

4

Reactant 2

HCID 24408BromineHCID 249009176-(6-Methyl-[1,2,4]triazolo[4,3-b]pyridazin-3-ylsulfanyl)-quinoline

Product 1

HCID 249009763-Bromo-6-(6-methyl-[1,2,4]triazolo[4,3-b]pyridazin-3-ylsulfanyl)-quinolineYield 90%

Reagents, catalysts & solvents 1

HCID 176Acetic AcidSolvent

Procedure

To a solution of 6-(6-methyl-[1,2,4]triazolo[4,3-b]pyridazin-3-ylsulfanyl)-quinoline (370 mg, 1.26 mmol) in glacial acetic acid (10 mL) was added bromine (0.324 mL, 6.31 mmol) dropwise. The reaction mixture was stirred at room temperature for 5 min then at 100° C. for 2 h. The reaction was cooled to room temperature, and the mixture was concentrated in vacuo. The residue was partitioned between 10% aqueous NaOH and 10% methanol/dichloromethane. The organic layer was separated, washed with 5% aqueous Na2SO3, and adsorbed on silica gel. Purification by flash chromatography on silica gel using a gradient of 0-5% methanol/dichloromethane afforded 422 mg of 3-bromo-6-(6-methyl-[1,2,4]triazolo[4,3-b]pyridazin-3-ylsulfanyl)-quinoline as a beige solid (90% yield): 1H NMR (DMSO-d6): δ 2.53 (s, 3H), 7.41 (d, 1H), 7.70 (dd, 1H), 7.87 (d, 1H), 7.99 (d, 1H), 8.41 (d, 1H), 8.66 (d, 1H), 8.93 (d, 1H); MS (m/z) 372, 374 [M+H+]+.

Workup

  1. waitat 100° C. for 2 h
  2. temperatureThe reaction was cooled to room temperature
  3. concentrationthe mixture was concentrated in vacuo
  4. customThe residue was partitioned between 10% aqueous NaOH and 10% methanol/dichloromethane
  5. customThe organic layer was separated
  6. washwashed with 5% aqueous Na2SO3
  7. customPurification by flash chromatography on silica gel using a gradient of 0-5% methanol/dichloromethane

Sources & evidence

ORD record
ord-3fe87e5cbfac4400b3818bf5a7ecfe16
Source dataset
uspto-grants-2013_08
Patent number
US08507489B2

Reaction notes

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