Boron tribromide → (4-amino-1-{[3-(4-fluorophenyl)isoxazol-5-yl]methyl}-6,7-dimethyl-1H-imidazo[4,5-c]pyridin-2-yl)methanol

HRID 606095Notes

Reaction equation

HRID 606095 reaction equation
C([O:3][CH2:4][C:5]1[N:6]([CH2:17][C:18]2[O:22][N:21]=[C:20]([C:23]3[CH:28]=[CH:27][C:26]([F:29])=[CH:25][CH:24]=3)[CH:19]=2)[C:7]2[C:12]([CH3:13])=[C:11]([CH3:14])[N:10]=[C:9]([NH2:15])[C:8]=2[N:16]=1)C.B(Br)(Br)Br>ClCCl.CO>[NH2:15][C:9]1[C:8]2[N:16]=[C:5]([CH2:4][OH:3])[N:6]([CH2:17][C:18]3[O:22][N:21]=[C:20]([C:23]4[CH:24]=[CH:25][C:26]([F:29])=[CH:27][CH:28]=4)[CH:19]=3)[C:7]=2[C:12]([CH3:13])=[C:11]([CH3:14])[N:10]=1

Participants

5

Reactant 2

HCID 25134Boron tribromideHCID 59026705HCID 59026705, compound

Product 1

HCID 59026687(4-amino-1-{[3-(4-fluorophenyl)isoxazol-5-yl]methyl}-6,7-dimethyl-1H-imidazo[4,5-c]pyridin-2-yl)methanolYield 35.6%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 6344DichloromethaneSolvent3×

Procedure

Under a nitrogen atmosphere, a solution of 2-(ethoxymethyl)-1-{[3-(4-fluorophenyl)isoxazol-5-yl]methyl}-6,7-dimethyl-1H-imidazo[4,5-c]pyridin-4-amine (0.8545 g, 2.161 mmol) in dichloromethane (50 mL) was cooled to about 6° C., and boron tribromide (5.4 mL of a 1 M solution in dichloromethane) was added dropwise. The reaction was heated at reflux under nitrogen for two hours and diluted with dichloromethane and methanol. The resulting solution was washed sequentially with aqueous potassium carbonate, water, and brine; dried over sodium sulfate; filtered; and concentrated under reduced pressure. The resulting solid was stirred in water overnight, isolated by filtration, purified by column chromatography on silica gel (eluting with 3% to 5% CMA in chloroform), and dried to provide 0.283 g of (4-amino-1-{[3-(4-fluorophenyl)isoxazol-5-yl]methyl}-6,7-dimethyl-1H-imidazo[4,5-c]pyridin-2-yl)methanol as a tan powder, mp 164.0-165.0° C.

Workup

  1. temperatureThe reaction was heated
  2. temperatureat reflux under nitrogen for two hours
  3. washThe resulting solution was washed sequentially with aqueous potassium carbonate, water, and brine
  4. dry with materialdried over sodium sulfate
  5. filtrationfiltered
  6. concentrationand concentrated under reduced pressure
  7. customisolated by filtration
  8. custompurified by column chromatography on silica gel (eluting with 3% to 5% CMA in chloroform)
  9. customdried

Sources & evidence

ORD record
ord-f1463bb9429d45e0bbfcbebb828c345a
Source dataset
uspto-grants-2011_03
Patent number
US07915281B2

Reaction notes

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