3-Cyanopyridine → (2-Amino-4,5-difluorophenyl)(pyridin-3-yl)methanone

HRID 29512

反応式

HRID 29512 の反応式
B(Cl)(Cl)Cl.[F:5][C:6]1[CH:11]=[CH:10][C:9]([NH2:12])=[CH:8][C:7]=1[F:13].[C:14]([C:16]1[CH:17]=[N:18][CH:19]=[CH:20][CH:21]=1)#N.Cl.[OH-:23].[Na+]>ClC=C(Cl)Cl.O.ClCCl>[NH2:12][C:9]1[C:10]([C:14]([C:16]2[CH:17]=[N:18][CH:19]=[CH:20][CH:21]=2)=[O:23])=[CH:11][C:6]([F:5])=[C:7]([F:13])[CH:8]=1

参加物

9

反応物 5

HCID 793-CyanopyridineHCID 313Hydrochloric AcidHCID 14798Sodium HydroxideHCID 25135Boron TrichlorideHCID 774693,4-Difluoroaniline

生成物 1

HCID 59788583(2-Amino-4,5-difluorophenyl)(pyridin-3-yl)methanone

試薬・触媒・溶媒 3

HCID 962Water溶媒HCID 6344Dichloromethane溶媒HCID 6575Trichloroethylene溶媒

実験手順

BCl3 (6.2 ml, 1M in DCM) was added dropwise to 1,2-difluoro-4-aminobenzene (0.5 g, 0.004 mol) in trichloroethylene (6.5 ml) at 0° C., the reaction mixture stirred for 15 min, then 3-Cyanopyridine (0.48 g, 0.005 mol) added and the solution warmed to room temperature and stirred for 30 min. The solution was then heated at 80-90° C. for 1 h. The resulting solution was refluxed at 160° C. for 4 hr, then stirred at room temprature over night, then 3N HCl was added to the reaction mixture and again refluxed at 110° C. for 1.5 h. The reaction mixture was cooled to RT and made basic (pH=12) with 6N NaOH. The reaction mixture was diluted with water and dichloromethane. The resulting two layers were separated and the aqueous layer was extracted with dichloromethane, dried over sodium sulfate and concentrated. The compound was purified by column chromatography on silica gel. 1H NMR (CDCl3): 6.29 (bs, 2H, NH2), 6.56 (m,1H), 7.25 (m,1H), 7.46 (m,1H), 7.93 (m,1H), 8.80 (m,1H), 8.85 (s, 1H). 13C NMR (CDCl3): 104.5, 104.7, 112.7, 121.3, 123.3, 135.1, 136.1, 142.5, 149.3, 149.5, 152.0, 153.8, 153.9, 156.3, 194.7. LC-MS m/e=235 (M+H)+. HPLC [c18 BDS 25 min column, flow=0.8 ml/min (70:30; ACN:0.1% TFA), rt=4.34 min].

後処理

  1. stirringstirred for 30 min
  2. temperatureThe solution was then heated at 80-90° C. for 1 h
  3. temperatureThe resulting solution was refluxed at 160° C. for 4 hr
  4. stirringstirred at room temprature over night
  5. temperatureagain refluxed at 110° C. for 1.5 h
  6. temperatureThe reaction mixture was cooled to RT
  7. customThe resulting two layers were separated
  8. extractionthe aqueous layer was extracted with dichloromethane
  9. dry with materialdried over sodium sulfate
  10. concentrationconcentrated
  11. customThe compound was purified by column chromatography on silica gel
  12. customHPLC [c18 BDS 25 min column, flow=0.8 ml/min (70:30; ACN:0.1% TFA), rt=4.34 min]

出典と根拠

ORDレコード
ord-208764f47c9d4c928247e9fd8401e36a
出典データセット
uspto-grants-2008_09
特許番号
US07420055B2

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