Dichloromethane → N-(2-Fluoro-5-(2-(4-methylpiperazin-1-yl)benzylcarbamoyl)phenyl)-7-(1-methyl-1H-pyrazol-5-yl)imidazo[1,2-a]pyridine-3-carboxamide

HRID 335267

反応式

HRID 335267 の反応式
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:36])[NH:21][CH2:22][C:23]4[CH:28]=[CH:27][CH:26]=[CH:25][C:24]=4[N:29]4[CH2:34][CH2:33][N:32]([CH3:35])[CH2:31][CH2:30]4)[CH:17]=[CH:16][C:15]=3[F:37])=[O:12])=[CH:9][N:10]=[C:4]2[CH:3]=1.[CH3:38][N:39]1[C:43](B2OC(C)(C)C(C)(C)O2)=[CH:42][CH:41]=[N:40]1.C(=O)([O-])[O-].[Cs+].[Cs+].C(Cl)Cl>CN(C=O)C.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]>[F:37][C:15]1[CH:16]=[CH:17][C:18]([C:20](=[O:36])[NH:21][CH2:22][C:23]2[CH:28]=[CH:27][CH:26]=[CH:25][C:24]=2[N:29]2[CH2:34][CH2:33][N:32]([CH3:35])[CH2:31][CH2:30]2)=[CH:19][C:14]=1[NH:13][C:11]([C:8]1[N:5]2[CH:6]=[CH:7][C:2]([C:43]3[N:39]([CH3:38])[N:40]=[CH:41][CH:42]=3)=[CH:3][C:4]2=[N:10][CH:9]=1)=[O:12]

参加物

7

反応物 4

HCID 6344DichloromethaneHCID 10796Cesium carbonateHCID 49129081-methyl-5-(tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazoleHCID 712830957-Bromo-N-(2-fluoro-5-(2-(4-methylpiperazin-1-yl)benzylcarbamoyl)phenyl)imidazo[1,2-a]pyridine-3-carboxamide

生成物 1

HCID 71283192N-(2-Fluoro-5-(2-(4-methylpiperazin-1-yl)benzylcarbamoyl)phenyl)-7-(1-methyl-1H-pyrazol-5-yl)imidazo[1,2-a]pyridine-3-carboxamide

試薬・触媒・溶媒 2

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)触媒HCID 6228Dimethylformamide溶媒

実験手順

A mixture comprising 7-bromo-N-(2-fluoro-5-(2-(4-methylpiperazin-1-yl)benzyl carbamoyl)phenyl)imidazo[1,2-a]pyridine-3-carboxamide (step 1) (120 mg, 0.212 mmol), 1-methyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole (44.2 mg, 0.212 mmol), cesium carbonate (69.1 mg, 0.212 mmol) and PdCl2(dppf).CH2Cl2 adduct (17.33 mg, 0.021 mmol) in DMF (5 ml) under N2 was heated at 85° C. for 2 hrs. After cooling to RT, the reaction mixture was partitioned between with EtOAc and water. A precipitate formed which was removed by filtration and discarded. The organic portion was separated and washed with NaHCO3, water, dried (MgSO4) and concentrated in vacuo. The crude product was purified by chromatography on silica eluting with 0-20% MeOH/DCM 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 column under gravity. The column was washed with MeOH and the combined eluents were concentrated in vacuo. The product was triturated with THF (1% MeOH) followed by ether to afford the title compound;

後処理

  1. customthe reaction mixture was partitioned between with EtOAc and water
  2. customA precipitate formed which
  3. customwas removed by filtration
  4. customThe organic portion was separated
  5. washwashed with NaHCO3, water
  6. dry with materialdried (MgSO4)
  7. concentrationconcentrated in vacuo
  8. customThe crude product was purified by chromatography on silica eluting with 0-20% MeOH/DCM
  9. concentrationconcentrated in vacuo
  10. dissolutionThe product was dissolved in MeOH
  11. washThe column was washed with MeOH
  12. concentrationthe combined eluents were concentrated in vacuo
  13. customThe product was triturated with THF (1% MeOH)

出典と根拠

ORDレコード
ord-a0be9d3b9e6640f5b9d6c17ed83cf3f2
出典データセット
uspto-grants-2014_11
特許番号
US08883819B2

関連ノート

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