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

HRID 1890954Notes

Reaction equation

HRID 1890954 reaction equation
[CH3:1][N:2]1[CH:6]=[C:5]([C:7]2[CH:8]=[CH:9][C:10]3[N:11]([C:13]([S:16][C:17]4[CH:18]=[C:19]5[C:24](=[CH:25][CH:26]=4)[N:23]=[CH:22][CH:21]=[CH:20]5)=[N:14][N:15]=3)[N:12]=2)[CH:4]=[N:3]1.[Br:27]Br>C(O)(=O)C>[Br:27][C:21]1[CH:22]=[N:23][C:24]2[C:19]([CH:20]=1)=[CH:18][C:17]([S:16][C:13]1[N:11]3[N:12]=[C:7]([C:5]4[CH:4]=[N:3][N:2]([CH3:1])[CH:6]=4)[CH:8]=[CH:9][C:10]3=[N:15][N:14]=1)=[CH:26][CH:25]=2

Participants

4

Reactant 2

HCID 24408BromineHCID 24779724Sgx-523

Product 1

HCID 689765583-Bromo-6-[6-(1-methyl-1h-pyrazol-4-yl)-[1,2,4]triazolo[4,3-b]pyridazin-3-ylsulfanyl]-quinolineYield 31.2%

Reagents, catalysts & solvents 1

HCID 176Acetic AcidSolvent

Procedure

To a solution of 6-[6-(1-methyl-1H-pyrazol-4-yl)-[1,2,4]triazolo[4,3-b]pyridazin-3-ylsulfanyl]-quinoline (1 g, 2.785 mmol) in glacial acetic acid (20 mL) was added bromine (0.716 mL, 13.93 mmol) dropwise. The reaction mixture was stirred at room temperature for 5 min then at 100° C. for 3 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/di-chloromethane. The organic layer was separated, washed with 1 M aqueous Na2S2O3, dried over sodium sulfate, filtered, and adsorbed on silica gel. Purification by flash chromatography on silica gel using a gradient of 0-7% methanol/dichloromethane afforded 381 mg of 3-bromo-6-[6-(1-methyl-1H-pyrazol-4-yl)-[1,2,4]triazolo[4,3-b]pyridazin-3-ylsulfanyl]-quinoline as a beige solid (31% yield): 1H NMR (DMSO-d6): δ 3.89 (s, 3H), 7.77 (dd, 1H), 7.80 (d, 1H), 7.99 (d, 1H), 8.00 (s, 1H), 8.43 (s, 1H), 8.48 (d, 1H), 8.68 (d, 1H), 8.92 (d, 1H); MS (m/z) 438, 440 [M+H+]+.

Workup

  1. waitat 100° C. for 3 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/di-chloromethane
  5. customThe organic layer was separated
  6. washwashed with 1 M aqueous Na2S2O3
  7. dry with materialdried over sodium sulfate
  8. filtrationfiltered
  9. customPurification by flash chromatography on silica gel using a gradient of 0-7% methanol/dichloromethane

Sources & evidence

ORD record
ord-36afa72f2c8745ad9bc958a135e39c9d
Source dataset
uspto-grants-2013_08
Patent number
US08507489B2

Reaction notes

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