Cesium carbonate → N-[[1-(3-chloro-5-cyclopropyl-2-pyridyl)cyclopropyl]methyl]-2-(trifluoromethyl)benzamide

HRID 578864ノート

反応式

HRID 578864 の反応式
Br[C:2]1[CH:3]=[C:4]([Cl:25])[C:5]([C:8]2([CH2:11][NH:12][C:13](=[O:24])[C:14]3[CH:19]=[CH:18][CH:17]=[CH:16][C:15]=3[C:20]([F:23])([F:22])[F:21])[CH2:10][CH2:9]2)=[N:6][CH:7]=1.[CH:26]1([B-](F)(F)F)[CH2:28][CH2:27]1.[K+].C(=O)([O-])[O-].[Cs+].[Cs+]>C1(C)C=CC=CC=1.O>[Cl:25][C:4]1[C:5]([C:8]2([CH2:11][NH:12][C:13](=[O:24])[C:14]3[CH:19]=[CH:18][CH:17]=[CH:16][C:15]=3[C:20]([F:23])([F:22])[F:21])[CH2:10][CH2:9]2)=[N:6][CH:7]=[C:2]([CH:26]2[CH2:28][CH2:27]2)[CH:3]=1

参加物

6

反応物 3

HCID 10796Cesium carbonateHCID 23697338Potassium cyclopropyltrifluoroborateHCID 89544470N-[[1-(5-bromo-3-chloro-2-pyridyl)cyclopropyl]methyl]-2-(trifluoromethyl)benzamide

生成物 1

HCID 71558842N-[[1-(3-chloro-5-cyclopropyl-2-pyridyl)cyclopropyl]methyl]-2-(trifluoromethyl)benzamide収率 44.7%

試薬・触媒・溶媒 2

HCID 962Water溶媒HCID 1140Toluene溶媒

反応条件

温度
100 °C

実験手順

150 mg of N-[[1-(5-bromo-3-chloro-2-pyridyl)cyclopropyl]methyl]-2-(trifluoromethyl)benzamide (step 4), 61 mg potassium cyclopropyltrifluoroborate and 340 mg cesium carbonate were dissolved in 3 ml of a mixture of toluene and water (3:1) in a microwave vial. The reaction mixture was degassed with argon for 1 min and 14 mg of [1,1′-Bis(diphenylphosphino)ferrocene]dichloropalladium(II) was added. The vial was sealed and the reaction mixture was then stirred at 100° C. in a microwave reactor for 30 min, then at 130° C. for 30 min. Then the mixture was cooled to ambient temperature, water was added and the reaction mixture was extracted with dichloromethane. The organic phase was dried with anhydrous sodium sulfate, filtered and concentrated. Crude material was obtained as a brown sticky solid, which was purified by flash chromatography on silica gel with heptane/ethyl acetate as a solvent. Thus, 61 mg of N-[[1-(3-chloro-5-cyclopropyl-2-pyridyl)cyclopropyl]methyl]-2-(trifluoromethyl)benzamide was obtained as a pale yellow sticky solid. 1H-NMR (CDCl3): 8.19 ppm (d, 1H), 7.65 ppm (d, 1H), 7.52 ppm (m, 2H), 7.40 ppm (d, 1H), 7.30 ppm (d, 1H), 6.20 ppm (s, 1H, broad), 3.68 ppm (d, 2H), 1.85 ppm (m, 1H), 1.05 ppm (m, 5H), 0.88 ppm (m, 1H), 0.70 ppm (m, 2H).

後処理

  1. customThe reaction mixture was degassed with argon for 1 min
  2. addition14 mg of [1,1′-Bis(diphenylphosphino)ferrocene]dichloropalladium(II) was added
  3. customThe vial was sealed
  4. waitat 130° C. for 30 min
  5. temperatureThen the mixture was cooled to ambient temperature
  6. additionwater was added
  7. extractionthe reaction mixture was extracted with dichloromethane
  8. dry with materialThe organic phase was dried with anhydrous sodium sulfate
  9. filtrationfiltered
  10. concentrationconcentrated
  11. customCrude material was obtained as a brown sticky solid, which
  12. customwas purified by flash chromatography on silica gel with heptane/ethyl acetate as a solvent

出典と根拠

ORDレコード
ord-12db9d251a2d4220b14781ab6ed69bc5
出典データセット
uspto-grants-2015_05
特許番号
US09040708B2

反応ノート

読み込み中…