Boron tribromide → 6,2'-Difluoro-4'-hydroxy-5'-[3-(1-hydroxy-1-methylethyl)imidazo[1,2-b][1,2,4]triazin-7-yl]biphenyl-2-carbonitrile

HRID 891868Notes

Reaction equation

HRID 891868 reaction equation
[F:1][C:2]1[CH:3]=[CH:4][CH:5]=[C:6]([C:30]#[N:31])[C:7]=1[C:8]1[CH:13]=[C:12]([C:14]2[N:18]3[N:19]=[CH:20][C:21]([C:23]([OH:26])([CH3:25])[CH3:24])=[N:22][C:17]3=[N:16][CH:15]=2)[C:11]([O:27]C)=[CH:10][C:9]=1[F:29].B(Br)(Br)Br>ClCCl>[F:1][C:2]1[CH:3]=[CH:4][CH:5]=[C:6]([C:30]#[N:31])[C:7]=1[C:8]1[CH:13]=[C:12]([C:14]2[N:18]3[N:19]=[CH:20][C:21]([C:23]([OH:26])([CH3:24])[CH3:25])=[N:22][C:17]3=[N:16][CH:15]=2)[C:11]([OH:27])=[CH:10][C:9]=1[F:29]

Participants

4

Reactant 2

HCID 25134Boron tribromideHCID 222400846,2'-Difluoro-5'-[3-(1-hydroxy-1-methylethyl)imidazo[1,2-b][1,2,4]triazin-7-yl]-4'-methoxybiphenyl-2-carbonitrile

Product 1

HCID 1355001016,2'-Difluoro-4'-hydroxy-5'-[3-(1-hydroxy-1-methylethyl)imidazo[1,2-b][1,2,4]triazin-7-yl]biphenyl-2-carbonitrileYield 16%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
-60 °C

Procedure

A solution of 6,2′-difluoro-5′-[3-(1-hydroxy-1-methylethyl)imidazo[1,2-b][1,2,4]triazin-7-yl]-4′-methoxybiphenyl-2-carbonitrile (0.18 g, 0.43 mmol) dissolved in anhydrous dichloromethane (10 ml) was cooled to −60° C. under nitrogen. Boron tribromide (2 M solution in dichloromethane, 1.28 ml, 2.57 mmol) was added with stirring. After 0.5 h the cooling bath was removed and the mixture was allowed to stir at room temperature for 4 h. Methanol (2 ml) was added and the mixture was shaken with 2 N NaOH (10 ml). Following neutralisation of the aqueous layer with 3 N HCl the solution was extracted with EtOAc (3×50 ml), dried (Na2SO4), filtered and evaporated to dryness. The residue was purified by flash column chromatography (silica gel, EtOAc) and crystallised from dichloromethane to give 28 mg (16%) of the title compound: 1H NMR (360 MHz, CDCl3) δ 1.70 (6H, s), 3.38 (1H, br s), 3.96 (3H, s), 7.38–7.49 (3H, m), 7.59–7.61 (1H, dd, J 0.9, 7.4), 8.10 (1H, d, J 8.0) 8.52 (1H, s), 8.71 (1H, s), 8.90 (1H, s); MS (ES+) m/z 408 [M+H]+.

Workup

  1. customAfter 0.5 h the cooling bath was removed
  2. stirringto stir at room temperature for 4 h
  3. additionMethanol (2 ml) was added
  4. stirringthe mixture was shaken with 2 N NaOH (10 ml)
  5. extractionwas extracted with EtOAc (3×50 ml)
  6. dry with materialdried (Na2SO4)
  7. filtrationfiltered
  8. customevaporated to dryness
  9. customThe residue was purified by flash column chromatography (silica gel, EtOAc)
  10. customcrystallised from dichloromethane

Sources & evidence

ORD record
ord-33e53a3f905f40a1b54da78b6fb5c03a
Source dataset
uspto-grants-2006_02
Patent number
US07005431B2

Reaction notes

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