Piperazine → N-(1-(6-chloro-2,3-dihydrobenzo[b][1,4]dioxin-8-yl)ethyl)-2-(methylsulfonyl)-5-(piperazin-1-yl)benzenamine

HRID 2426032ノート

反応式

HRID 2426032 の反応式
ClC1C=C(C(N)C)C2OCCOC=2C=1.FC1C=C(F)C=CC=1S(C)(=O)=O.C(N(C(C)C)CC)(C)C.[Cl:36][C:37]1[CH:46]=[C:45]([CH:47]([NH:49][C:50]2[CH:55]=[C:54](F)[CH:53]=[CH:52][C:51]=2[S:57]([CH3:60])(=[O:59])=[O:58])[CH3:48])[C:40]2[O:41][CH2:42][CH2:43][O:44][C:39]=2[CH:38]=1.[NH:61]1[CH2:66][CH2:65][NH:64][CH2:63][CH2:62]1>CN(C)C=O.C(#N)C.O>[Cl:36][C:37]1[CH:46]=[C:45]([CH:47]([NH:49][C:50]2[CH:55]=[C:54]([N:61]3[CH2:66][CH2:65][NH:64][CH2:63][CH2:62]3)[CH:53]=[CH:52][C:51]=2[S:57]([CH3:60])(=[O:59])=[O:58])[CH3:48])[C:40]2[O:41][CH2:42][CH2:43][O:44][C:39]=2[CH:38]=1

参加物

9

反応物 5

HCID 4837PiperazineHCID 81531Diisopropylethylamine2 回HCID 27583362,4-Difluoro-1-(methylsulfonyl)benzeneHCID 587073121-(6-Chloro-2,3-dihydrobenzo[b][1,4]dioxin-8-yl)ethanamineHCID 67147312N-(1-(6-chloro-2,3-dihydrobenzo[b][1,4]dioxin-8-yl)ethyl)-5-fluoro-2-(methylsulfonyl)benzenamine

生成物 1

HCID 11633830N-(1-(6-chloro-2,3-dihydrobenzo[b][1,4]dioxin-8-yl)ethyl)-2-(methylsulfonyl)-5-(piperazin-1-yl)benzenamine収率 80%

試薬・触媒・溶媒 3

HCID 962Water溶媒HCID 6228Dimethylformamide溶媒HCID 6342Acetonitrile溶媒

実験手順

A solution of 1-(6-chloro-2,3-dihydrobenzo[b][1,4]dioxin-8-yl)ethanamine (130 mg, 0.61 mmol), 2,4-difluoro-1-(methylsulfonyl)benzene (116 mg, 0.61 mmol) and diisopropylethylamine (314 mg, 2.43 mmol) in N,N-dimethylformamide (2 mL) was stirred at 110° C. for 16 h. The reaction was cooled to room temperature, poured over water and extracted with diethyl ether. The solvent was concentrated in vacuo to collect 53.4 mg of the desired product, which was used for the next reaction without further purification. A solution of N-(1-(6-chloro-2,3-dihydrobenzo[b][1,4]dioxin-8-yl)ethyl)-5-fluoro-2-(methylsulfonyl)benzenamine (53.4 mg, 0.14 mmol), piperazine (239 mg, 2.76 mmol) and N,N-diisopropylethylamine (0.25 mL, 1.38 mmol) in acetonitrile (2 mL) was stirred at reflux for 16 h. The reaction mixture was cooled down and concentrated under reduced pressure. The residue was taken up in dichloromethane, washed with water, dried and concentrated in vacuo. The crude product was purified by silica chromatography (10% ethyl acetate in hexanes) to yield 50 mg (80%) of desired product. 1H NMR (400 MHz, CDCl3): δ 7.58 (d, 1H), 6.82 (d, 1H), 6.76 (d, 1H), 6.60 (d, 1H), 6.23 (d, 1H), 5.87 (d, 1H), 4.73 (m, 1H), 4.28 (m, 4H), 3.24 (m, 4H), 3.05 (s, 3H), 3.03 (m, 4H), 1.54 (d, 3H); MS (ESI) m/z: 452.3 (M++1).

後処理

  1. extractionextracted with diethyl ether
  2. concentrationThe solvent was concentrated in vacuo
  3. customto collect 53.4 mg of the desired product, which
  4. customwas used for the next reaction without further purification
  5. temperatureat reflux for 16 h
  6. temperatureThe reaction mixture was cooled down
  7. concentrationconcentrated under reduced pressure
  8. washwashed with water
  9. customdried
  10. concentrationconcentrated in vacuo
  11. customThe crude product was purified by silica chromatography (10% ethyl acetate in hexanes)

出典と根拠

ORDレコード
ord-7bb9398d3dbe4794a886d8137c9567c8
出典データセット
uspto-grants-2011_06
特許番号
US07968538B2

反応ノート

読み込み中…