Cesium carbonate → HCID 178522380, compound

HRID 1710723Notes

Reaction equation

HRID 1710723 reaction equation
Cl[C:2]1[N:7]=[C:6]([NH:8][C:9]([CH:11]2[CH2:13][CH2:12]2)=[O:10])[CH:5]=[N:4][C:3]=1[C:14]1[CH:19]=[CH:18][N+:17]([O-:20])=[CH:16][C:15]=1[F:21].[N:22]1[CH:27]=[CH:26][CH:25]=[C:24](B(O)O)[CH:23]=1.C([O-])([O-])=O.[Cs+].[Cs+].O1CCOCC1>O>[F:21][C:15]1[CH:16]=[N+:17]([O-:20])[CH:18]=[CH:19][C:14]=1[C:3]1[N:4]=[CH:5][C:6]([NH:8][C:9]([CH:11]2[CH2:13][CH2:12]2)=[O:10])=[N:7][C:2]=1[C:24]1[CH:23]=[N:22][CH:27]=[CH:26][CH:25]=1

Participants

6

Reactant 4

HCID 10796Cesium carbonateHCID 312751,4-DioxaneHCID 27343783-Pyridinylboronic acidHCID 178522381HCID 178522381, compound

Product 1

HCID 178522380HCID 178522380, compoundYield 56%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Conditions

Temperature
90 °C

Procedure

In a sealed tube three cycles of vacuum and argon were applied to a mixture of the N-[6-chloro-5-(3-fluoro-1-oxidopyridin-4-yl)pyrazin-2-yl]cyclopropanecarboxamide (2.23 g, 7.22 mmol), pyridin-3-ylboronic acid (1.15 g, 9.39 mmol) and Cs2CO3 (7.06 g, 21.66 mmol). A solution of 1,4-dioxane:H2O (64 mL, 9:1) was added and argon was bubbled for 5 min, after which, PdCl2dppfCH2Cl2 (0.59 g, 0.72 mmol) was added and argon was again bubbled other 5 min. The reaction mixture was heated at 90° C. for 1 h. Upon the reaction completion the 1,4-dioxane was concentrated in vaccuo, and the obtained residue was adsorbed onto silica gel with 10% MeOH/THF (150 mL) and purified by column chromatography on silica gel eluting with a MeOH/EtOAc gradient (0→20%). The green solid obtained was precipitated with 1% MeOH/CH2Cl2 (5 mL), and washed with 1% MeOH/CH2Cl2 (3×3 mL), CH2Cl2 (3×5 mL), 1% MeOH/Et2O (3×5 mL) and Et2O (4×5 mL) to yield the title compound as a white powder (1.41 g, 56%).

Workup

  1. customargon was bubbled for 5 min
  2. additionafter which, PdCl2dppfCH2Cl2 (0.59 g, 0.72 mmol) was added
  3. concentrationUpon the reaction completion the 1,4-dioxane was concentrated in vaccuo
  4. custompurified by column chromatography on silica gel eluting with a MeOH/EtOAc gradient (0→20%)
  5. customThe green solid obtained
  6. customwas precipitated with 1% MeOH/CH2Cl2 (5 mL)
  7. washwashed with 1% MeOH/CH2Cl2 (3×3 mL), CH2Cl2 (3×5 mL), 1% MeOH/Et2O (3×5 mL) and Et2O (4×5 mL)

Sources & evidence

ORD record
ord-843e919442f545b5bf07ae1a0c2a9291
Source dataset
uspto-grants-2010_09
Patent number
US07790728B2

Reaction notes

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