4-Bromo-1-trityl-1H-imidazole → 3-(1H-Imidazol-4-yl)-6-(6-methyl-[1,2,4]triazolo[4,3-b]pyridazin-3-ylmethyl)-quinoline

HRID 655290Notes

Reaction equation

HRID 655290 reaction equation
Br[C:2]1[N:3]=[CH:4][N:5](C(C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[CH:6]=1.C([Mg]Br)C.Br[C:31]1[CH:32]=[N:33][C:34]2[C:39]([CH:40]=1)=[CH:38][C:37]([CH2:41][C:42]1[N:46]3[N:47]=[C:48]([CH3:51])[CH:49]=[CH:50][C:45]3=[N:44][N:43]=1)=[CH:36][CH:35]=2>O1CCCC1.[Cl-].[Cl-].[Zn+2]>[NH:3]1[CH:2]=[C:6]([C:31]2[CH:32]=[N:33][C:34]3[C:39]([CH:40]=2)=[CH:38][C:37]([CH2:41][C:42]2[N:46]4[N:47]=[C:48]([CH3:51])[CH:49]=[CH:50][C:45]4=[N:44][N:43]=2)=[CH:36][CH:35]=3)[N:5]=[CH:4]1

Participants

6

Reactant 3

HCID 27732744-Bromo-1-trityl-1H-imidazoleHCID 593202953-Bromo-6-(6-methyl-[1,2,4]triazolo[4,3-b]pyridazin-3-ylmethyl)-quinolineHCID 178418443HCID 178418443, compound

Product 1

HCID 1784235183-(1H-Imidazol-4-yl)-6-(6-methyl-[1,2,4]triazolo[4,3-b]pyridazin-3-ylmethyl)-quinolineYield 8%

Reagents, catalysts & solvents 2

HCID 3007855ZincchlorideCatalystHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
70 °C

Procedure

To a solution of 4-bromo-1-trityl-1H-imidazole (103 mg, 0.24 mmol, 1.0 equiv) in tetrahydrofuran (1 mL) was added ethyl magnesium bromide (3M in diethylether, 0.094 mL, 0.28 mmol, 1.2 equiv) and the reaction was stirred for 90 min. ZnCl2 (38 mg, 0.28 mmol, 1.2 equiv) was then added and the solution stirred for an additional 90 min. Tetrakis (triphenylphosphine)palladium (2 mg, 0.024 mmol, 0.10 equiv) and 3-bromo-6-(6-methyl-[1,2,4]triazolo[4,3-b]pyridazin-3-ylmethyl)-quinoline (100 mg, 0.28 mmol, 1.2 equiv) were added and the solution heated at 70° C. for 18 hours. The solvent was removed in vacuo and the residue absorbed onto silica gel and purified by flash chromatography (SiO2, CH2Cl2:CH3OH 100:0-80:20 to return 6-(6-methyl-[1,2,4]triazolo[4,3-b]pyridazin-3-ylmethyl)-3-(3-trityl-3H-imidazol-4-yl)-quinoline. The trityl group was removed by stirring the compound in methanolic hydrochloric acid (0.5 N) for 3 hours. The volatiles were removed in vacuo and the residue stirred in ethanol and collected via filtration and dried to return the title compound (5.6 mg, 8% yield). Analytical data presented in Table 2.

Workup

  1. stirringthe solution stirred for an additional 90 min
  2. customThe solvent was removed in vacuo
  3. customthe residue absorbed onto silica gel
  4. custompurified by flash chromatography (SiO2, CH2Cl2:CH3OH 100:0-80:20
  5. customThe trityl group was removed
  6. stirringby stirring the compound in methanolic hydrochloric acid (0.5 N) for 3 hours
  7. customThe volatiles were removed in vacuo
  8. stirringthe residue stirred in ethanol
  9. filtrationcollected via filtration
  10. customdried

Sources & evidence

ORD record
ord-8bbf4d1a692f4873a51bd12db44baf90
Source dataset
uspto-grants-2011_12
Patent number
US08071581B2

Reaction notes

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