Dimethylformamide → 6-bromo-2-(4-fluorophenyl)-N-methylimidazo[1,2-a]pyridine-3-carboxamide

HRID 219331Notes

Reaction equation

HRID 219331 reaction equation
[Br:1][C:2]1[CH:3]=[CH:4][C:5]2[N:6]([C:8]([C:18]([OH:20])=O)=[C:9]([C:11]3[CH:16]=[CH:15][C:14]([F:17])=[CH:13][CH:12]=3)[N:10]=2)[CH:7]=1.C(Cl)(=O)C(Cl)=O.[CH3:27][N:28](C=O)C.CN>C1COCC1.ClCCCl>[Br:1][C:2]1[CH:3]=[CH:4][C:5]2[N:6]([C:8]([C:18]([NH:28][CH3:27])=[O:20])=[C:9]([C:11]3[CH:12]=[CH:13][C:14]([F:17])=[CH:15][CH:16]=3)[N:10]=2)[CH:7]=1

Participants

7

Reactant 4

HCID 6228DimethylformamideHCID 6329MethylamineHCID 65578Oxalyl chlorideHCID 592338406-Bromo-2-(4-fluorophenyl)imidazo[1,2-a]pyridine-3-carboxylic acid

Product 1

HCID 592336946-bromo-2-(4-fluorophenyl)-N-methylimidazo[1,2-a]pyridine-3-carboxamideYield 76%

Reagents, catalysts & solvents 2

HCID 111,2-DichloroethaneSolventHCID 8028TetrahydrofuranSolvent

Procedure

6-Bromo-2-(4-fluorophenyl)imidazo[1,2-a]pyridine-3-carboxylic acid (250 mg, 0.746 mmol) was slurried into DCE (8 mL) and then oxalyl chloride (0.30 mL, 3.4 mmol) was added and the slurry was stirred for 5 min. Then DMF (50 μL, 0.65 mmol) was added (foaming) and the slurry was stirred 1 h before methanamine (5 mL, 10 mmol) 2M in THF (exothermic) and TEA (˜3 mL) (exothermic) were added. The reaction was stirred at rt overnight. The reaction was partitioned between water (˜30 mL) and DCM/MeOH (9/1, 3×30 mL). The combined organics were concentrated to dryness and the residue was slurried in MeOH/EtOAc (1:1˜40 mL) and filtered to collect 6-bromo-2-(4-fluorophenyl)-N-methylimidazo[1,2-a]pyridine-3-carboxamide (172 mg, 0.494 mmol, 66% yield) as a white solid. 1H NMR (500 MHz, DMSO-d6) δ ppm 8.92 (s, 1H), 8.25 (s, 1H), 7.85 (d, J=7.9 Hz, 1H), 7.83 (d, J=7.9 Hz, 1H), 7.69 (d, J=9.5 Hz, 1H), 7.56 (d, J=9.5 Hz, 1H), 7.33 (d, J=8.5 Hz, 1H), 7.31 (d, J=8.5 Hz, 1H), 2.79 (d, J=4.0 Hz, 3H). LC-MS retention time 1.73 min; ink 348, 350 (MH+). LC data was recorded on a Shimadzu LC-10AS liquid chromatograph equipped with a Phenomenex-Luna 10u C18 4.6×50 mm column using a SPD-10AV UV-Vis detector at a detector wave length of 220 nM. The elution conditions employed a flow rate of 5 mL/min, a gradient of 100% solvent A/0% solvent B to 0% solvent A/100% solvent B, a gradient time of 3 min, a hold time of 1 min, and an analysis time of 4 min where solvent A was 5% acetonitrile/95% H2O/10 mM ammonium acetate and solvent B was 5% H2O/95% acetonitrile/10 mM ammonium acetate. MS data was determined using a Micromass Platform for LC in electrospray mode.

Workup

  1. additionwere added
  2. stirringThe reaction was stirred at rt overnight
  3. customThe reaction was partitioned between water (˜30 mL) and DCM/MeOH (9/1, 3×30 mL)
  4. concentrationThe combined organics were concentrated to dryness
  5. filtrationfiltered

Sources & evidence

ORD record
ord-594b49122ee64c05a9d49488b76be8ba
Source dataset
uspto-grants-2012_06
Patent number
US08198449B2

Reaction notes

Loading…