Cesium carbonate → 3-(4-Aminophenyl)-5-{1-[(2S)-1,4-dioxan-2-ylmethyl]-1H-pyrazol-4-yl}pyridin-2-amine

HRID 1428115Notes

Reaction equation

HRID 1428115 reaction equation
CC1(C)C(C)(C)OB([C:9]2[CH:10]=[N:11][NH:12][CH:13]=2)O1.C(=O)([O-])[O-].[Cs+].[Cs+].CS(O[CH2:26][C@H:27]1[CH2:32][O:31][CH2:30][CH2:29][O:28]1)(=O)=O.[NH2:33][C:34]1[CH:39]=[CH:38][C:37]([C:40]2[C:41]([NH2:47])=[N:42][CH:43]=[C:44](Br)[CH:45]=2)=[CH:36][CH:35]=1>O1CCOCC1.[I-].C([N+](CCCC)(CCCC)CCCC)CCC.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2].ClCCl.C(OCC)(=O)C>[NH2:33][C:34]1[CH:39]=[CH:38][C:37]([C:40]2[C:41]([NH2:47])=[N:42][CH:43]=[C:44]([C:9]3[CH:13]=[N:12][N:11]([CH2:26][C@H:27]4[CH2:32][O:31][CH2:30][CH2:29][O:28]4)[CH:10]=3)[CH:45]=2)=[CH:36][CH:35]=1

Participants

9

Reactant 4

HCID 10796Cesium carbonateHCID 27740104-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazoleHCID 682889763-(4-Aminophenyl)-5-bromopyridin-2-amineHCID 86609782(2R)-1,4-dioxan-2-ylmethyl methanesulfonate

Product 1

HCID 867000683-(4-Aminophenyl)-5-{1-[(2S)-1,4-dioxan-2-ylmethyl]-1H-pyrazol-4-yl}pyridin-2-amineYield 71%

Reagents, catalysts & solvents 4

HCID 67553Tetrabutylammonium IodideCatalystHCID 178418807HCID 178418807, compoundCatalystHCID 8857Ethyl AcetateSolventHCID 312751,4-DioxaneSolvent

Procedure

4-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole (10.0 g) was added to a suspension of cesium carbonate (75.6 g) in 1,4-dioxane (200 ml), followed by stirring. (2R)-1,4-Dioxan-2-ylmethyl methanesulfonate (12.1 g) and tetra-n-butylammonium iodide (0.95 g) were then added, and the mixture was stirred at 100° C. for six hours. After cooling the reaction solution to room temperature, 3-(4-aminophenyl)-5-bromopyridin-2-amine (10.9 g) and [1,1′-bis(diphenylphosphino)ferrocene]palladium(II) dichloride-dichloromethane adduct (2.1 g) were added, and the mixture was stirred at 100° C. for one hour. The reaction solution was returned to room temperature, ethyl acetate was added, and the insoluble matter was then removed by filtration. The resulting organic layer was sequentially washed with water and brine and then dried over anhydrous sodium sulfate. The solvent was distilled off under reduced pressure, and the residue was purified by silica gel column chromatography [chloroform:methanol=99:1->19:1 (v/v)] to give 10.3 g of the title compound as a solid.

Workup

  1. stirringthe mixture was stirred at 100° C. for six hours
  2. stirringthe mixture was stirred at 100° C. for one hour
  3. customwas returned to room temperature
  4. customthe insoluble matter was then removed by filtration
  5. washThe resulting organic layer was sequentially washed with water and brine
  6. dry with materialdried over anhydrous sodium sulfate
  7. distillationThe solvent was distilled off under reduced pressure
  8. customthe residue was purified by silica gel column chromatography [chloroform:methanol=99:1->19:1 (v/v)]

Sources & evidence

ORD record
ord-69a61730e452476bb4d37b20566c34e4
Source dataset
uspto-grants-2015_01
Patent number
US08933103B2

Reaction notes

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