Dichloromethane → 7-(1-Methyl-1H-pyrazol-4-yl)-imidazo[1,2-a]pyridine-3-carboxylic Acid {5-[2-(2,6-cis-dimethyl-piperidin-1-yl)-ethylcarbamoyl]-2-fluoro-phenyl}-amide Hydrochloride

HRID 335278Notes

Reaction equation

HRID 335278 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:32])[NH:21][CH2:22][CH2:23][N:24]4[C@H:29]([CH3:30])[CH2:28][CH2:27][CH2:26][C@@H:25]4[CH3:31])[CH:17]=[CH:16][C:15]=3[F:33])=[O:12])=[CH:9][N:10]=[C:4]2[CH:3]=1.[CH3:34][N:35]1[CH:39]=[C:38](B(O)O)[CH:37]=[N:36]1.C(=O)([O-])[O-].[Cs+].[Cs+].C(Cl)[Cl:50]>COCCOC.O>[ClH:50].[CH3:30][C@H:29]1[CH2:28][CH2:27][CH2:26][C@@H:25]([CH3:31])[N:24]1[CH2:23][CH2:22][NH:21][C:20]([C:18]1[CH:17]=[CH:16][C:15]([F:33])=[C:14]([NH:13][C:11]([C:8]2[N:5]3[CH:6]=[CH:7][C:2]([C:38]4[CH:37]=[N:36][N:35]([CH3:34])[CH:39]=4)=[CH:3][C:4]3=[N:10][CH:9]=2)=[O:12])[CH:19]=1)=[O:32]

Participants

7

Reactant 4

HCID 6344DichloromethaneHCID 10796Cesium carbonateHCID 112635011-Methyl-1H-pyrazole-4-boronic acidHCID 712832197-bromo-N-(5-(2-(2,6-cis-dimethylpiperidin-1-yl)ethylcarbamoyl)-2-fluorophenyl)imidazo[1,2-a]pyridine-3-carboxamide2×

Product 1

HCID 866956747-(1-Methyl-1H-pyrazol-4-yl)-imidazo[1,2-a]pyridine-3-carboxylic Acid {5-[2-(2,6-cis-dimethyl-piperidin-1-yl)-ethylcarbamoyl]-2-fluoro-phenyl}-amide Hydrochloride

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 80711,2-DimethoxyethaneSolvent

Procedure

7-Bromo-N-(5-(2-(2,6-cis-dimethylpiperidin-1-yl)ethylcarbamoyl)-2-fluorophenyl)imidazo[1,2-a]pyridine-3-carboxamide (Intermediate 4C) (50 mg, 0.097 mmol), 1-methyl-1H-pyrazol-4-ylboronic acid (24.38 mg, 0.194 mmol) and cesium carbonate (126 mg, 0.387 mmol) was dissolved in DME (215 μl)/water (108 μl) to form a solution. Nitrogen was bubbled though the reaction mixture for 2 minutes. PdCl2(dppf).CH2Cl2 adduct (3.95 mg, 4.84 μmol) was added and the mixture was heated using microwave radiation at 100° C. for 15 mins. The water was removed and the organic portion was dry loaded onto silica. The crude product was purified by chromatography on silica eluting with 0-20% 2M NH3 in MeOH and the product fractions were combined and concentrated in vacuo. The product was dissolved in MeOH and passed through a 1 g 2,4,6-trimercaptotriazine silica. The solvent was removed in vacuo and the residue was triturated with ether. The resulting precipitate was filtered and dried in the oven to afford the title compound;

Workup

  1. customto form a solution
  2. customNitrogen was bubbled though the reaction mixture for 2 minutes
  3. temperaturethe mixture was heated
  4. customat 100° C.
  5. customfor 15 mins
  6. customThe water was removed
  7. customthe organic portion was dry
  8. customThe crude product was purified by chromatography on silica eluting with 0-20% 2M NH3 in MeOH
  9. concentrationconcentrated in vacuo
  10. dissolutionThe product was dissolved in MeOH
  11. customThe solvent was removed in vacuo
  12. customthe residue was triturated with ether
  13. filtrationThe resulting precipitate was filtered
  14. customdried in the oven

Sources & evidence

ORD record
ord-9c5060acdc5746d390f1f3defa858ed8
Source dataset
uspto-grants-2014_11
Patent number
US08883819B2

Reaction notes

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