Trifluoroacetic acid → N-(2-amino-5-phenylphenyl)-4-{1,8-diazaspiro[4.5]decan-8-ylcarbonyl}benzamide

HRID 2360555ノート

反応式

HRID 2360555 の反応式
[C:1](Cl)(=[O:11])[C:2]1[CH:10]=[CH:9][C:5]([C:6](Cl)=[O:7])=[CH:4][CH:3]=1.[NH2:13][C:14]1[CH:15]=[C:16]([C:28]2[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=2)[CH:17]=[CH:18][C:19]=1[NH:20]C(=O)OC(C)(C)C.C(N(C(C)C)CC)(C)C.[N:43]1(C(OC(C)(C)C)=O)[C:47]2([CH2:52][CH2:51][NH:50][CH2:49][CH2:48]2)[CH2:46][CH2:45][CH2:44]1.C(=O)([O-])[O-].FC(F)(F)C(O)=O>ClCCl.CN(C)C=O>[NH2:20][C:19]1[CH:18]=[CH:17][C:16]([C:28]2[CH:29]=[CH:30][CH:31]=[CH:32][CH:33]=2)=[CH:15][C:14]=1[NH:13][C:1](=[O:11])[C:2]1[CH:10]=[CH:9][C:5]([C:6]([N:50]2[CH2:51][CH2:52][C:47]3([NH:43][CH2:44][CH2:45][CH2:46]3)[CH2:48][CH2:49]2)=[O:7])=[CH:4][CH:3]=1

参加物

9

反応物 6

HCID 6422Trifluoroacetic acidHCID 7488Terephthaloyl chlorideHCID 19660Carbonate IonHCID 81531Diisopropylethylamine2 回HCID 34178602tert-Butyl 1,8-diazaspiro(4.5)decane-1-carboxylateHCID 57717454N-(3-Amino[1,1'-biphenyl]-4-yl)-carbamic Acid tert-Butyl Ester

生成物 1

HCID 25218563N-(2-amino-5-phenylphenyl)-4-{1,8-diazaspiro[4.5]decan-8-ylcarbonyl}benzamide

試薬・触媒・溶媒 2

HCID 6228Dimethylformamide溶媒HCID 6344Dichloromethane溶媒

実験手順

To a solution of stirring terephthaloyl chloride (50 mg, 0.246 mmol) in 3 mL dichloromethane was added tert-butyl (3-aminobiphenyl-4-yl)carbamate (70 mg, 0.246 mmol) slowly over a period of 10 minutes, followed by the addition of diisopropylethylamine (43 μL, 0.246 mmol). The reaction mixture was allowed to stir for 30 min. at room temperature. Tert-butyl 1,8-diazaspiro[4,5]decane-1-carboxylate (59 mg, 0.246 mmol) was then added, followed by the addition of diisopropylethylamine (43 μL, 0.246 mmol). The reaction mixture was allowed to stir for 1 hour at room temperature. The reaction mixture became cloudy. Argonaut MP-Carbonate scavenging resin (255 mg, 0.738 mmol) was then added and stirred overnight at room temperature. The mixture was then fully dissolved by adding 3 mL dimethylformamide, filtered from scavenging resin, and concentrated. Added dichloromethane (1 mL) and stirred to form suspension, then treated with trifluoroacetic acid (1 mL). The reaction mixture was concentrated after 2 hours of stirring at room temperature and the crude residue was purified by reverse-phase chromatography (5-75-95% acetonitrile/water with 0.1% formic acid). The appropriate fractions were combined and lyophilized. MS (ESI+): cal'd [M+H]+ 455.2, obs'd 455.1.

後処理

  1. stirringto stir for 1 hour at room temperature
  2. stirringstirred overnight at room temperature
  3. dissolutionThe mixture was then fully dissolved
  4. filtrationfiltered
  5. concentrationconcentrated
  6. stirringAdded dichloromethane (1 mL) and stirred
  7. customto form suspension
  8. concentrationThe reaction mixture was concentrated after 2 hours
  9. stirringof stirring at room temperature
  10. customthe crude residue was purified by reverse-phase chromatography (5-75-95% acetonitrile/water with 0.1% formic acid)

出典と根拠

ORDレコード
ord-68a281b9b95e4ef5b933f2e9d875a28d
出典データセット
uspto-grants-2014_04
特許番号
US08686020B2

反応ノート

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