Dichloromethane → Methyl 4-(3-(5-(3,4-difluorobenzylcarbamoyl)-2-fluorophenylcarbamoyl)imidazo[1,2-a]pyridin-7-yl)-2-fluorobenzoate

HRID 335288Notes

Reaction equation

HRID 335288 reaction equation
Br[C:2]1[CH:7]=[CH:6][N:5]2[C:8]([C:11]([NH:13][C:14]3[CH:19]=[C:18]([C:20](=[O:31])[NH:21][CH2:22][C:23]4[CH:28]=[CH:27][C:26]([F:29])=[C:25]([F:30])[CH:24]=4)[CH:17]=[CH:16][C:15]=3[F:32])=[O:12])=[CH:9][N:10]=[C:4]2[CH:3]=1.[F:33][C:34]1[CH:43]=[C:42](B2OC(C)(C)C(C)(C)O2)[CH:41]=[CH:40][C:35]=1[C:36]([O:38][CH3:39])=[O:37].C(=O)([O-])[O-].[Cs+].[Cs+].C(Cl)Cl>O.COCCOC>[F:30][C:25]1[CH:24]=[C:23]([CH:28]=[CH:27][C:26]=1[F:29])[CH2:22][NH:21][C:20]([C:18]1[CH:17]=[CH:16][C:15]([F:32])=[C:14]([NH:13][C:11]([C:8]2[N:5]3[CH:6]=[CH:7][C:2]([C:42]4[CH:41]=[CH:40][C:35]([C:36]([O:38][CH3:39])=[O:37])=[C:34]([F:33])[CH:43]=4)=[CH:3][C:4]3=[N:10][CH:9]=2)=[O:12])[CH:19]=1)=[O:31]

Participants

7

Reactant 4

HCID 6344DichloromethaneHCID 10796Cesium carbonateHCID 22171528Methyl 2-fluoro-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzoateHCID 712831817-bromo-N-(5-(3,4-difluorobenzylcarbamoyl)-2-fluorophenyl)imidazo[1,2-a]pyridine-3-carboxamide2×

Product 1

HCID 71283111Methyl 4-(3-(5-(3,4-difluorobenzylcarbamoyl)-2-fluorophenylcarbamoyl)imidazo[1,2-a]pyridin-7-yl)-2-fluorobenzoate

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 80711,2-DimethoxyethaneSolvent

Procedure

7-Bromo-N-(5-(3,4-difluorobenzylcarbamoyl)-2-fluorophenyl)imidazo[1,2-a]pyridine-3-carboxamide (Intermediate 3A) (500 mg, 0.993 mmol), methyl 2-fluoro-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzoate (306 mg, 1.093 mmol) and cesium carbonate (1295 mg, 3.97 mmol) in water (2 ml)/DME (5 ml) were mixed to give a suspension. The mixture was degassed with nitrogen and PdCl2(dppf).CH2Cl2 adduct (40.6 mg, 0.050 mmol) was added. The reaction mixture was heated using microwave radiation at 100° C. for 1 hr and partitioned between EtOAc and water. The organic portion was separated, dried (MgSO4) and concentrated in vacuo. The crude product was triturated with MeOH/diethyl ether to afford the title compound;

Workup

  1. customto give a suspension
  2. customThe mixture was degassed with nitrogen and PdCl2(dppf)
  3. temperatureThe reaction mixture was heated
  4. customat 100° C.
  5. customfor 1 hr
  6. custompartitioned between EtOAc and water
  7. customThe organic portion was separated
  8. dry with materialdried (MgSO4)
  9. concentrationconcentrated in vacuo
  10. customThe crude product was triturated with MeOH/diethyl ether

Sources & evidence

ORD record
ord-168ee033b1e845cb8e436f61ce13fe02
Source dataset
uspto-grants-2014_11
Patent number
US08883819B2

Reaction notes

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