4-Bromo-2-fluoroaniline → HCID 68546216, compound

HRID 1446706Notes

Reaction equation

HRID 1446706 reaction equation
[CH2:1]([N:3]([CH2:20][CH3:21])[CH2:4][C:5]1[CH:10]=[C:9]([C:11]2[CH:16]=[CH:15][N:14]3[CH:17]=[CH:18][N:19]=[C:13]3[CH:12]=2)[CH:8]=[CH:7][N:6]=1)[CH3:2].Br[C:23]1[CH:28]=[CH:27][C:26]([NH2:29])=[C:25]([F:30])[CH:24]=1.C([O-])(=O)C.[K+]>CS(C)=O>[CH2:20]([N:3]([CH2:4][C:5]1[CH:10]=[C:9]([C:11]2[CH:16]=[CH:15][N:14]3[C:17]([C:23]4[CH:28]=[CH:27][C:26]([NH2:29])=[C:25]([F:30])[CH:24]=4)=[CH:18][N:19]=[C:13]3[CH:12]=2)[CH:8]=[CH:7][N:6]=1)[CH2:1][CH3:2])[CH3:21]

Participants

5

Reactant 3

HCID 1230504-Bromo-2-fluoroanilineHCID 517044Potassium AcetateHCID 68546399HCID 68546399, compound

Product 1

HCID 68546216HCID 68546216, compoundYield 21%

Reagents, catalysts & solvents 1

HCID 679Dimethyl SulfoxideSolvent

Conditions

Temperature
100 °C

Procedure

Combine diethyl-(4-imidazo[1,2-a]pyridin-7-yl-pyridin-2-ylmethyl)-amine (1.00 g, 3.57 mmol), 4-bromo-2-fluoro-phenylamine (1.36 g, 7.13 mmol) and potassium acetate (0.700 g, 7.13 mmol) in DMSO (4 mL). De-gas the mixture for 10 minutes with N2. Add dichlorobis(triphenylphosphine) palladium (II) (0.250 g, 0.357 mmol); stir the reaction mixture for 14 hours under N2 at 100° C. Purify using an SCX cartridge (10 g VARIAN bond elut), eluting with 1:1 methanol:dichloromethane, then 1:1 2 M NH3 in methanol:dichloromethane. Purify via reverse phase chromatography using a 25 cm by 50.8 mm (i.d.) column w/10 micron particles (MeCN/0.03% HCl H2O (5:95) to 100% MeCN; 30 min). Compound obtained is partitioned between ethyl acetate and 1 N NaOH. Wash the organic layer with aqueous saturated sodium chloride, dry over magnesium sulfate, filter, and concentrate to afford the title compound (0.286 g, 21%). MS(ES), m/z 390 (M+1).

Workup

  1. customDe-gas the mixture for 10 minutes with N2
  2. customPurify
  3. washeluting with 1:1 methanol
  4. customPurify via reverse phase chromatography
  5. customby 50.8 mm (i.d.) column w/10 micron particles (MeCN/0.03% HCl H2O (5:95) to 100% MeCN; 30 min)
  6. customCompound obtained
  7. customis partitioned between ethyl acetate and 1 N NaOH
  8. washWash the organic layer with aqueous saturated sodium chloride
  9. dry with materialdry over magnesium sulfate
  10. filtrationfilter
  11. concentrationconcentrate

Sources & evidence

ORD record
ord-38bc1d92346a4932b019c97b00cfcf75
Source dataset
uspto-grants-2010_02
Patent number
US07666879B2

Reaction notes

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