Tetrafluoroboric acid → 2-[7-(5-Bromo-4-fluoro-2-methoxyphenyl)imidazo[1,2-b][1,2,4]triazin-3-yl]propan-2-ol

HRID 891866Notes

Reaction equation

HRID 891866 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[N:12]3[N:13]=[CH:14][C:15]([C:17]([OH:20])([CH3:19])[CH3:18])=[N:16][C:11]3=[N:10][CH:9]=2)=[C:4]([O:21][CH3:22])[CH:3]=1.F[B-](F)(F)F.[H+].[Br:29]N1C(=O)CCC1=O>C(#N)C>[Br:29][C:7]1[C:2]([F:1])=[CH:3][C:4]([O:21][CH3:22])=[C:5]([C:8]2[N:12]3[N:13]=[CH:14][C:15]([C:17]([OH:20])([CH3:19])[CH3:18])=[N:16][C:11]3=[N:10][CH:9]=2)[CH:6]=1

Participants

5

Reactant 3

HCID 28118Tetrafluoroboric acidHCID 67184N-bromobutanimideHCID 222400807-(4-Fluoro-2-methoxyphenyl)-α,α-dimethylimidazo[1,2-b][1,2,4]triazine-3-methanol

Product 1

HCID 222401002-[7-(5-Bromo-4-fluoro-2-methoxyphenyl)imidazo[1,2-b][1,2,4]triazin-3-yl]propan-2-ol

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

To a cold (−20° C.) solution of 2-[7-(4-fluoro-2-methoxyphenyl)imidazo[1,2-b][1,2,4]triazin-3-yl]propan-2-ol (0.4 g, 1.32 mmol) in acetonitrile (4 ml) under nitrogen was added tetrafluoroboric acid (54 wt % solution in Et2O, 0.21 ml, 1.59 mmol) and then N-bromosuccinimide (0.28 g, 1.59 mmol) slowly such that the internal temperature remained less than −10° C. After addition the cooling bath was removed and the reaction mixture was allowed to warm to room temperature. Stirring at this temperature continued for 16 h. A 40% aqueous solution of NaHSO3 (10 ml) was added and the reaction mixture extracted with EtOAc (3×50 ml). Organic extracts were washed with water (50 ml), saturated aqueous brine (50 ml), dried (Na2SO4) and concentrated under reduced pressure. The residue was purified by flash chromatography (silica gel, EtOAc) to give a quantitative yield of the title compound: 1H NMR (400 MHz, CDCl3) δ 1.71 (6H, s), 3.47 (1H, s), 3.89 (3H, s), 6.86 (1H, d, J 10.3), 8.21 (1H, d, J 7.9), 8.29 (1H, s), 8.74 (1H, s); MS (ES+) m/z 381, 383 [M+H]+.

Workup

  1. customremained less than −10° C
  2. additionAfter addition the cooling bath
  3. customwas removed
  4. additionA 40% aqueous solution of NaHSO3 (10 ml) was added
  5. extractionthe reaction mixture extracted with EtOAc (3×50 ml)
  6. washOrganic extracts were washed with water (50 ml), saturated aqueous brine (50 ml)
  7. dry with materialdried (Na2SO4)
  8. concentrationconcentrated under reduced pressure
  9. customThe residue was purified by flash chromatography (silica gel, EtOAc)

Sources & evidence

ORD record
ord-ede1e61019a348edbfd0188c34da7ebb
Source dataset
uspto-grants-2006_02
Patent number
US07005431B2

Reaction notes

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