N-Hydroxyacetamidine → Methyl [3,5-bis(trifluoromethyl)benzyl]{[2'-methoxy-5'-(3-methyl-1,2,4-oxadiazol-5-yl)-4-(trifluoromethyl)biphenyl-2-yl]methyl}carbamate

HRID 17092

反応式

HRID 17092 の反応式
C(Cl)(=O)C(Cl)=O.[F:7][C:8]([F:48])([F:47])[C:9]1[CH:10]=[C:11]([CH:40]=[C:41]([C:43]([F:46])([F:45])[F:44])[CH:42]=1)[CH2:12][N:13]([CH2:18][C:19]1[CH:24]=[C:23]([C:25]([F:28])([F:27])[F:26])[CH:22]=[CH:21][C:20]=1[C:29]1[C:34]([O:35][CH3:36])=[CH:33][CH:32]=[C:31]([C:37]([OH:39])=O)[CH:30]=1)[C:14]([O:16][CH3:17])=[O:15].[C:49](=[N:52]O)([NH2:51])[CH3:50]>CN(C)C=O.C(Cl)Cl>[F:44][C:43]([F:46])([F:45])[C:41]1[CH:40]=[C:11]([CH:10]=[C:9]([C:8]([F:7])([F:48])[F:47])[CH:42]=1)[CH2:12][N:13]([CH2:18][C:19]1[CH:24]=[C:23]([C:25]([F:28])([F:27])[F:26])[CH:22]=[CH:21][C:20]=1[C:29]1[CH:30]=[C:31]([C:37]2[O:39][N:52]=[C:49]([CH3:50])[N:51]=2)[CH:32]=[CH:33][C:34]=1[O:35][CH3:36])[C:14](=[O:15])[O:16][CH3:17]

参加物

6

反応物 3

HCID 30926N-HydroxyacetamidineHCID 65578Oxalyl chlorideHCID 115924972'-{[[3,5-Bis(trifluoromethyl)benzyl](methoxycarbonyl)amino]methyl}-6-methoxy-4'-(trifluoromethyl)biphenyl-3-carboxylic acid

生成物 1

HCID 11563674Methyl [3,5-bis(trifluoromethyl)benzyl]{[2'-methoxy-5'-(3-methyl-1,2,4-oxadiazol-5-yl)-4-(trifluoromethyl)biphenyl-2-yl]methyl}carbamate

試薬・触媒・溶媒 2

HCID 6228Dimethylformamide触媒2 回HCID 6344Dichloromethane溶媒

実験手順

Oxalyl chloride (0.14 mL, 0.28 mmol) and a few drops of dimethylformamide were added to a solution of the title compound from Example 145 (86 mg, 0.14 mmol) in methylene chloride. The reaction mixture was stirred at room temperature for 1 h then concentrated in vacuo. The crude product was re-dissolved in anhydrous dichloroethane, and acetamide oxime (16 mg, 0.21 mmol) was added along with a few drops of dimethylformamide to increase solubility. The reaction was heated to and maintained at reflux overnight. Once the reaction cooled to room temperature, the solvent was removed through evaporation. The oil was taken up in methylene chloride, washed with water, then brine, dried over anhydrous sodium sulfate, filtered and concentrated. The title compound was obtained by preparative thin layer chromatography using 50% EtOAc/hexane. 1H NMR (CDCl3, 600 MHz) δ 8.15 (s, 1H), 7.86 (s, 1H), 7.71 (s, 1H), 7.62 (d, J=8.4 Hz, 1H), 7.43-7.56 (m, 3H), 7.35 (d, J=7.8 Hz, 1H), 7.07 (m, 1H), 4.20-4.60 (m, 4H), 3.81 (s, 3H), 3.70 (m, 3H), 2.46 (s, 3H). LC-MS (M+1) 647.9 (4.40 min).

後処理

  1. concentrationthen concentrated in vacuo
  2. dissolutionThe crude product was re-dissolved in anhydrous dichloroethane
  3. temperatureto increase solubility
  4. temperatureThe reaction was heated to and
  5. temperaturemaintained
  6. temperatureat reflux overnight
  7. temperatureOnce the reaction cooled to room temperature
  8. customthe solvent was removed through evaporation
  9. washwashed with water
  10. dry with materialbrine, dried over anhydrous sodium sulfate
  11. filtrationfiltered
  12. concentrationconcentrated

出典と根拠

ORDレコード
ord-3b966f8e234140ce9a70b189ec935769
出典データセット
uspto-grants-2010_06
特許番号
US07737295B2

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