Pyridine → Methyl 3-(7-bromoimidazo[1,2-a]pyridine-3-carboxamido)-4-methylbenzoate

HRID 335310

Reaction equation

HRID 335310 reaction equation
[Br:1][C:2]1[CH:7]=[CH:6][N:5]2[C:8]([C:11](NC3C=C(C=CC=3F)C(O)=O)=[O:12])=[CH:9][N:10]=[C:4]2[CH:3]=1.S(Cl)(Cl)=O.[NH2:28][C:29]1[CH:30]=[C:31]([CH:36]=[CH:37][C:38]=1[CH3:39])[C:32]([O:34][CH3:35])=[O:33].N1C=CC=CC=1>CCOC(C)=O>[Br:1][C:2]1[CH:7]=[CH:6][N:5]2[C:8]([C:11]([NH:28][C:29]3[CH:30]=[C:31]([CH:36]=[CH:37][C:38]=3[CH3:39])[C:32]([O:34][CH3:35])=[O:33])=[O:12])=[CH:9][N:10]=[C:4]2[CH:3]=1

Participants

6

Reactant 4

HCID 1049PyridineHCID 24386Thionyl ChlorideHCID 337778Methyl 3-amino-4-methylbenzoateHCID 712834433-[(7-Bromo-imidazo[1,2-a]pyridine-3-carbonyl)-amino]-4-fluorobenzoic acid2×

Product 1

HCID 71283103Methyl 3-(7-bromoimidazo[1,2-a]pyridine-3-carboxamido)-4-methylbenzoate

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent

Procedure

A mixture comprising 7-bromoimidazo[1,2-a]pyridine-3-carboxylic acid (Intermediate 1A step 3) (750 mg, 3.11 mmol) and thionyl chloride (5 ml, 68.5 mmol) under N2 was heated at reflux for 2 hrs. The mixture was concentrated in vacuo and azeotroped with toluene. Methyl 3-amino-4-methylbenzoate (514 mg, 3.11 mmol) (pre-dried at 45° C.) was added followed by pyridine (5 ml) and the mixture was stirred at room temperature under N2 overnight. The reaction mixture was diluted with EtOAc and washed with sat. NaHCO3, brine, H2O, dried (MgSO4) and concentrated in vacuo. Purification by chromatography on silica eluting with 50-100% EtOAc in iso-hexane afforded the title compound as an orange solid;

Workup

  1. temperatureat reflux for 2 hrs
  2. concentrationThe mixture was concentrated in vacuo
  3. customazeotroped with toluene
  4. washwashed with sat. NaHCO3, brine, H2O
  5. dry with materialdried (MgSO4)
  6. concentrationconcentrated in vacuo
  7. customPurification by chromatography on silica eluting with 50-100% EtOAc in iso-hexane

Sources & evidence

ORD record
ord-973abd30f88f43e5a53172b267f448f1
Source dataset
uspto-grants-2014_11
Patent number
US08883819B2

Linked notes

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