Water → Ethyl 5-(5-(6-aminopyridin-2-yl)-2-chlorobenzamido)-1-phenyl-1H-pyrazole-3-carboxylate

HRID 522125Notes

Reaction equation

HRID 522125 reaction equation
[NH2:1][C:2]1[N:7]=[C:6](Br)[CH:5]=[CH:4][CH:3]=1.C(=O)([O-])[O-].[Na+].[Na+].O.[Cl:16][C:17]1[CH:41]=[CH:40][C:39](B2OC(C)(C)C(C)(C)O2)=[CH:38][C:18]=1[C:19]([NH:21][C:22]1[N:26]([C:27]2[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=2)[N:25]=[C:24]([C:33]([O:35][CH2:36][CH3:37])=[O:34])[CH:23]=1)=[O:20]>O1CCOCC1>[NH2:1][C:2]1[N:7]=[C:6]([C:39]2[CH:40]=[CH:41][C:17]([Cl:16])=[C:18]([CH:38]=2)[C:19]([NH:21][C:22]2[N:26]([C:27]3[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=3)[N:25]=[C:24]([C:33]([O:35][CH2:36][CH3:37])=[O:34])[CH:23]=2)=[O:20])[CH:5]=[CH:4][CH:3]=1

Participants

6

Reactant 4

HCID 962WaterHCID 10340Sodium CarbonateHCID 3008092-Amino-6-bromopyridineHCID 123572737ethyl 5-(2-chloro-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzamido)-1-phenyl-1H-pyrazole-3-carboxylate

Product 1

HCID 118456164Ethyl 5-(5-(6-aminopyridin-2-yl)-2-chlorobenzamido)-1-phenyl-1H-pyrazole-3-carboxylateYield 51%

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent

Conditions

Temperature
100 °C

Procedure

6-amino-2-bromopyridine (835.5 mg, 4.83 mmol), sodium carbonate (1.39 g, 13.2 mmol) and water (0.5 mL) were added to the solution of ethyl 5-(2-chloro-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzamido)-1-phenyl-1H-pyrazole-3-carboxylate in dioxane obtained in Preparation 5. The reaction was degassed with nitrogen for 30 minutes before the addition of Pd(dppf)Cl2 with further degassing for 10 minutes. The reaction was heated to 100° C. for 16 hours. The reaction was cooled and eluted through a pad of silica, eluting with EtOAc (50 mL). The organic solution was washed with water (50 mL) dried over magnesium sulfate and concentrated in vacuo. The residue was purified using silica gel column chromatography eluting with 30-50% EtOAc in heptanes to afford the title compound as a pale yellow solid (1.02 g, 51%).

Workup

  1. customobtained in Preparation 5
  2. customThe reaction was degassed with nitrogen for 30 minutes before the addition of Pd(dppf)Cl2
  3. customwith further degassing for 10 minutes
  4. temperatureThe reaction was cooled
  5. washeluted through a pad of silica
  6. washeluting with EtOAc (50 mL)
  7. washThe organic solution was washed with water (50 mL)
  8. dry with materialdried over magnesium sulfate
  9. concentrationconcentrated in vacuo
  10. customThe residue was purified
  11. washeluting with 30-50% EtOAc in heptanes

Sources & evidence

ORD record
ord-3ee25716b9044a6a889443f9c26d9a62
Source dataset
uspto-grants-2016_05
Patent number
US09328096B2

Reaction notes

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