Trifluoroacetic acid → HCID 66671673、化合物

HRID 446528ノート

反応式

HRID 446528 の反応式
[C:1]([O:5][C:6]([N:8]([CH3:35])[CH2:9][CH2:10][CH2:11][N:12]([CH3:34])[C:13]([C:15]1[CH:20]=[CH:19][C:18]([NH:21][CH2:22][CH2:23][O:24][CH2:25][CH2:26][C:27](OC(C)(C)C)=[O:28])=[CH:17][CH:16]=1)=[O:14])=[O:7])([CH3:4])([CH3:3])[CH3:2].FC(F)(F)C(O)=O.C(N(CC)CC)C.C(OC(OC(C)(C)C)=O)(OC(C)(C)C)=O.C(Cl)(=O)C(C)(C)C.[C:72]1([C:92]2[CH:97]=[CH:96][CH:95]=[CH:94][CH:93]=2)[CH:77]=[CH:76][CH:75]=[CH:74][C:73]=1[NH:78][C:79](=[O:91])[O:80][CH:81]1[CH2:86][CH2:85][N:84]([CH2:87][CH2:88][NH:89][CH3:90])[CH2:83][CH2:82]1>C(Cl)Cl>[C:72]1([C:92]2[CH:97]=[CH:96][CH:95]=[CH:94][CH:93]=2)[CH:77]=[CH:76][CH:75]=[CH:74][C:73]=1[NH:78][C:79](=[O:91])[O:80][CH:81]1[CH2:86][CH2:85][N:84]([CH2:87][CH2:88][N:89]([C:27](=[O:28])[CH2:26][CH2:25][O:24][CH2:23][CH2:22][NH:21][C:18]2[CH:19]=[CH:20][C:15]([C:13](=[O:14])[N:12]([CH2:11][CH2:10][CH2:9][N:8]([C:6]([O:5][C:1]([CH3:2])([CH3:3])[CH3:4])=[O:7])[CH3:35])[CH3:34])=[CH:16][CH:17]=2)[CH3:90])[CH2:83][CH2:82]1

参加物

8

反応物 6

HCID 6422Trifluoroacetic acidHCID 8471Triethylamine2 回HCID 62493Pivaloyl chlorideHCID 90495Di-tert-butyl dicarbonateHCID 566436031-(2-(Methylamino)ethyl)piperidin-4-yl [1,1'-biphenyl]-2-ylcarbamateHCID 86663437HCID 86663437、化合物

生成物 1

HCID 66671673HCID 66671673、化合物収率 66.6%

試薬・触媒・溶媒 1

HCID 6344Dichloromethane溶媒

実験手順

The compound (188 mg, 0.381 mmol) obtained in Example 28e was dissolved in methylene chloride (4 mL), trifluoroacetic acid (2 mL) was added under ice cooling, and the mixture was stirred at room temperature for 2.5 hours. The solvent was evaporated under reduced pressure, and moisture was removed from the resulting residue azeotropically with toluene (×2). The resulting residue was dissolved in methylene chloride (4 mL), triethylamine (0.318 mL, 2.29 mmol) and di-tert-butyl dicarbonate (183 mg, 0.838 mmol) were added, and the mixture was stirred at room temperature for 18.5 hours. The solvent was evaporated under reduced pressure, the resulting residue was dissolved in methylene chloride (4 mL), triethylamine (79 μL, 0.572 mmol) and pivaloyl chloride (49 μL, 0.400 mmol) were added under ice cooling, and the mixture was stirred at room temperature for 20 minutes. 1-[2-(Methylamino)ethyl]piperidin-4-yl biphenyl-2-ylcarbamate (296 mg, 0.838 mmol) was added under ice cooling, and the mixture was stirred at room temperature for 2 hours. The solvent was evaporated under reduced pressure, and the resulting residue was purified by NH silica gel column chromatography (ethyl acetate:methanol=50:1, v/v) to give the title compound (196 mg; yield, 66%) as a white solid.

後処理

  1. customThe solvent was evaporated under reduced pressure, and moisture
  2. customwas removed from the resulting residue azeotropically with toluene (×2)
  3. dissolutionThe resulting residue was dissolved in methylene chloride (4 mL)
  4. stirringthe mixture was stirred at room temperature for 18.5 hours
  5. customThe solvent was evaporated under reduced pressure
  6. dissolutionthe resulting residue was dissolved in methylene chloride (4 mL)
  7. stirringthe mixture was stirred at room temperature for 20 minutes
  8. stirringthe mixture was stirred at room temperature for 2 hours
  9. customThe solvent was evaporated under reduced pressure
  10. customthe resulting residue was purified by NH silica gel column chromatography (ethyl acetate

出典と根拠

ORDレコード
ord-896c9e11361f4e5397fcc0039f5f0811
出典データセット
uspto-grants-2013_07
特許番号
US08476253B2

反応ノート

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