2-(4-Methyl-1-piperazinyl)benzenemethanamine → 7-Bromo-N-(2-fluoro-5-(2-(4-methylpiperazin-1-yl)benzylcarbamoyl)phenyl)imidazo[1,2-a]pyridine-3-carboxamide

HRID 335266Notes

Reaction equation

HRID 335266 reaction equation
[Br:1][C:2]1[CH:7]=[CH:6][N:5]2[C:8]([C:11]([NH:13][C:14]3[CH:15]=[C:16]([CH:21]=[CH:22][C:23]=3[F:24])[C:17]([O:19]C)=O)=[O:12])=[CH:9][N:10]=[C:4]2[CH:3]=1.[CH3:25][N:26]1[CH2:31][CH2:30][N:29]([C:32]2[CH:37]=[CH:36][CH:35]=[CH:34][C:33]=2[CH2:38][NH2:39])[CH2:28][CH2:27]1>C1(C)C=CC=CC=1>[Br:1][C:2]1[CH:7]=[CH:6][N:5]2[C:8]([C:11]([NH:13][C:14]3[CH:15]=[C:16]([C:17](=[O:19])[NH:39][CH2:38][C:33]4[CH:34]=[CH:35][CH:36]=[CH:37][C:32]=4[N:29]4[CH2:28][CH2:27][N:26]([CH3:25])[CH2:31][CH2:30]4)[CH:21]=[CH:22][C:23]=3[F:24])=[O:12])=[CH:9][N:10]=[C:4]2[CH:3]=1

Participants

4

Reactant 2

HCID 27955682-(4-Methyl-1-piperazinyl)benzenemethanamine2×HCID 712828883-[(7-Bromo-imidazo[1,2-a]pyridine-3-carbonyl)-amino]-4-fluoro-benzoic Acid Methyl Ester2×

Product 1

HCID 712830957-Bromo-N-(2-fluoro-5-(2-(4-methylpiperazin-1-yl)benzylcarbamoyl)phenyl)imidazo[1,2-a]pyridine-3-carboxamide

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Conditions

Temperature
80 °C

Procedure

Methyl 3-(7-bromoimidazo[1,2-a]pyridine-3-carboxamido)-4-fluorobenzoate (Intermediate 1A)(1.08 g, 2.75 mmol), TBD (0.383 g, 2.75 mmol) and (2-(4-methylpiperazin-1-yl)phenyl)methanamine (0.565 g, 2.75 mmol) in toluene (35 ml) were heated to 80° C. for 6 hrs. A further portion of TBD (0.06 g, 0.431 mmol) and (2-(4-methylpiperazin-1-yl)phenyl)methanamine (0.100 g, 0.487 mmol) were added and the mixture was heated at 80° C. overnight. TBD (0.06 g, 0.431 mmol) was added and heating continued at 110° C. overnight. Toluene was removed in vacuo and the resulting solid was partitioned between aqueous sodium bicarbonate solution and EtOAc. The organic portion was washed with sodium bicarbonate solution (2×50 ml) and concentrated in vacuo. The resulting oil was dissolved in MeOH and purified by chromatography on silica eluting with 0-10% MeOH in DCM. The fractions were combined and the solvent removed in vacuo. The resulting solid was recrystallised from EtOAc (50 ml) to afford the title compound;

Workup

  1. additionTBD (0.06 g, 0.431 mmol) was added
  2. temperatureheating
  3. customToluene was removed in vacuo
  4. customthe resulting solid was partitioned between aqueous sodium bicarbonate solution and EtOAc
  5. washThe organic portion was washed with sodium bicarbonate solution (2×50 ml)
  6. concentrationconcentrated in vacuo
  7. dissolutionThe resulting oil was dissolved in MeOH
  8. custompurified by chromatography on silica eluting with 0-10% MeOH in DCM
  9. customthe solvent removed in vacuo
  10. customThe resulting solid was recrystallised from EtOAc (50 ml)

Sources & evidence

ORD record
ord-cab7e342f905462e8ea9d4005a10a6be
Source dataset
uspto-grants-2014_11
Patent number
US08883819B2

Reaction notes

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