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

HRID 1428115노트

반응식

HRID 1428115 반응식
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

참가 물질

9

반응물 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

생성물 1

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

시약·촉매·용매 4

HCID 67553Tetrabutylammonium Iodide촉매HCID 178418807HCID 178418807, 화합물촉매HCID 8857Ethyl Acetate용매HCID 312751,4-Dioxane용매

실험 절차

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.

후처리

  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)]

출처 및 근거

ORD 기록
ord-69a61730e452476bb4d37b20566c34e4
출처 데이터셋
uspto-grants-2015_01
특허 번호
US08933103B2

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