Potassium Phosphate, Tribasic → 1-(3-Imidazo[1,2-a]pyridin-3-yl-phenyl)-3-(2,2,2-trifluoro-ethyl)-urea

HRID 1093528ノート

反応式

HRID 1093528 の反応式
Br[C:2]1[N:6]2[CH:7]=[CH:8][CH:9]=[CH:10][C:5]2=[N:4][CH:3]=1.[O-]P([O-])([O-])=O.[K+].[K+].[K+].CC1(C)C(C)(C)OB([C:27]2[CH:28]=[C:29]([NH:33][C:34]([NH:36][CH2:37][C:38]([F:41])([F:40])[F:39])=[O:35])[CH:30]=[CH:31][CH:32]=2)O1>O.O1CCOCC1>[N:4]1[CH:3]=[C:2]([C:31]2[CH:30]=[C:29]([NH:33][C:34]([NH:36][CH2:37][C:38]([F:39])([F:40])[F:41])=[O:35])[CH:28]=[CH:27][CH:32]=2)[N:6]2[CH:7]=[CH:8][CH:9]=[CH:10][C:5]=12

参加物

6

反応物 3

HCID 62657Potassium Phosphate, TribasicHCID 3279513-Bromoimidazo[1,2-a]pyridineHCID 574976911-[3-(4,4,5,5-Tetramethyl-[1,3,2]dioxaborolan-2-yl)-phenyl]-3-(2,2,2-trifluoro-ethyl)-urea

生成物 1

HCID 665921101-(3-Imidazo[1,2-a]pyridin-3-yl-phenyl)-3-(2,2,2-trifluoro-ethyl)-urea

試薬・触媒・溶媒 2

HCID 962Water溶媒HCID 312751,4-Dioxane溶媒

反応条件

温度
90 °C

実験手順

To a stirred solution of 3-Bromoimidazo[1,2-a]pyridine (commercially available, ex Bionet, 394 mg, 2 mmol) was added a solution of K3PO4 (1.27 g, 6 mmol) in H2O (2 mls). 1-[3-(4,4,5,5-Tetramethyl-[1,3,2]dioxaborolan-2-yl)-phenyl]-3-(2,2,2-trifluoro-ethyl)-urea (905 mg, 2.5 mmol) dissolved in dioxane (8 ml) was added to the reaction mixture and the reaction deoxygenated by evacuation and refill of the flask with N2 (×2). PdCl2dppf (150 mg, 0.2 mmol) was added and the reaction mixture was deoxygenated (×3). The reaction mixture was heated at 90° C. for 16 h, cooled to RT and partitioned between CH2Cl2 and H2O, then filtered. The layers were separated and the aqueous layer further extracted with CH2Cl2. The organic fractions were combined and passed through a phase separating cartridge, then the solvent removed in vacuo. The residue was purified using a SCX cartridge, washing with MeOH and eluting with 2M NH3/MeOH. The resulting solid was further purified by silica column chromatography (0-3% 2M NH3/MeOH in CH2Cl2) to afford a beige solid (335 mg). MS: [M+H]+=335.

後処理

  1. additionwas added to the reaction mixture
  2. customthe reaction deoxygenated by evacuation and refill of the flask with N2 (×2)
  3. customthe reaction mixture was deoxygenated (×3)
  4. temperaturecooled to RT
  5. custompartitioned between CH2Cl2 and H2O
  6. filtrationfiltered
  7. customThe layers were separated
  8. extractionthe aqueous layer further extracted with CH2Cl2
  9. customseparating cartridge
  10. customthe solvent removed in vacuo
  11. customThe residue was purified
  12. washwashing with MeOH
  13. washeluting with 2M NH3/MeOH
  14. customThe resulting solid was further purified by silica column chromatography (0-3% 2M NH3/MeOH in CH2Cl2)

出典と根拠

ORDレコード
ord-d8d2ac7cafb14086bd66f3edf26a7572
出典データセット
uspto-grants-2012_03
特許番号
US08131527B1

反応ノート

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