1-[Bis-(4-hydroxyphenyl)methyl]-1H-[1,2,4]triazole → 1-[Bis-(3-bromo-4-hydroxyphenyl)methyl]-1H-[1,2,4]triazole

HRID 19960Notes

Reaction equation

HRID 19960 reaction equation
[OH:1][C:2]1[CH:7]=[CH:6][C:5]([CH:8]([C:14]2[CH:19]=[CH:18][C:17]([OH:20])=[CH:16][CH:15]=2)[N:9]2[CH:13]=[N:12][CH:11]=[N:10]2)=[CH:4][CH:3]=1.[Br-:21].[Br-:22].[Br-].C([N+](C)(C)C)C1C=CC=CC=1.C([N+](C)(C)C)C1C=CC=CC=1.C([N+](C)(C)C)C1C=CC=CC=1>C(Cl)Cl.CO.O.CCOC(C)=O>[Br:21][C:16]1[CH:15]=[C:14]([CH:8]([C:5]2[CH:6]=[CH:7][C:2]([OH:1])=[C:3]([Br:22])[CH:4]=2)[N:9]2[CH:13]=[N:12][CH:11]=[N:10]2)[CH:19]=[CH:18][C:17]=1[OH:20]

Participants

6

Reactant 2

HCID 219769051-[Bis-(4-hydroxyphenyl)methyl]-1H-[1,2,4]triazoleHCID 53442637Benzyltrimethylammoniumtribromide

Product 1

HCID 219768921-[Bis-(3-bromo-4-hydroxyphenyl)methyl]-1H-[1,2,4]triazole

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 8857Ethyl AcetateSolventHCID 21226129Dichloromethane methanolSolvent2×

Procedure

To a stirred solution of 1-[Bis-(4-hydroxyphenyl)methyl]-1H-[1,2,4]triazole (STX267, 500 mg, 1.87 mmol) in CH2Cl2/MeOH 1:1 (40 ml) at −78° C. under nitrogen, a solution of benzyltrimethylammonium tribromide (1.49 g, 3.74 mmol) in CH2Cl2/MeOH 1:1 (10 ml) was added dropwise over 45 min. The orange mixture was kept at 0° C. for 7 h and then at room temperature overnight, at which time the solution had become colorless. The reaction mixture was evaporated and the residue that obtained was dissolved in a mixture water (100 mL) and EtOAc (100 mL). The aqueous layer was separated and was further extracted with EtOAc (2×50 mL). The organic extracts were combined and washed with brine, dried (Na2SO4) and evaporated. The crude product was fractionated by flash chromatography (hexane/ethyl acetate, 1:3) and the second fraction that collected gave JRL01105 (STX356) (485 mg) as white solid at about 97% purity; δH (400 MHz, DMSO-d6) 6.90 (1H, s, CH), 6.93 (2H, d, J 8.6 Hz), 7.03 (2H, dd, J 2.1 and 8.6 Hz), 7.30 (2H, d, J 2.1 Hz), 8.06 (1H, s), 8.56 (1H, s) and 10.45 (2H, br s, exchanged with D2O, 2×OH). The main impurity was the mono-brominated derivative of STX356. A small quantity of this fraction was further purified by semi-preparative HPLC (Waters PrepLC RP18, 25×10 mm, flow rate: 10 mL/min, mobile phase: MeOH/H2O, 60:40). The fraction with a retention time of 5.5 nm in was collected and upon evaporation gave a white solid; m.p. 198-205° C. (dec.). Found: C, 42.2; H, 2.65; N, 9.79; C15H11Br2N3O2 requires C, 42.38, H, 2.61, N, 9.89.

Workup

  1. customat room temperature
  2. customovernight
  3. customThe reaction mixture was evaporated
  4. customthe residue that obtained
  5. customThe aqueous layer was separated
  6. extractionwas further extracted with EtOAc (2×50 mL)
  7. washwashed with brine
  8. dry with materialdried (Na2SO4)
  9. customevaporated
  10. customthe second fraction that collected
  11. customgave JRL01105 (STX356) (485 mg) as white solid at about 97% purity
  12. customA small quantity of this fraction was further purified by semi-preparative HPLC (Waters PrepLC RP18, 25×10 mm, flow rate: 10 mL/min, mobile phase: MeOH/H2O, 60:40)
  13. customThe fraction with a retention time of 5.5 nm in was collected and upon evaporation
  14. customgave a white solid

Sources & evidence

ORD record
ord-51e4072d137f4ce39b82538f57875854
Source dataset
uspto-grants-2010_06
Patent number
US07745472B2

Reaction notes

Loading…