1,1'-Carbonyldiimidazole → 4-(3,3-Dimethyl-butyl)-piperazine-1-carboxylic Acid 4-(3,6-dimethyl-4,10-dihydro-3H-2,3,4,9-tetraaza-benzo[f]azulene-9-carbonyl)-2-fluoro-benzylamide

HRID 220790ノート

反応式

HRID 220790 の反応式
CCN(C(C)C)C(C)C.[C:10](N1C=CN=C1)(N1C=CN=C1)=[O:11].Cl.[NH2:23][CH2:24][C:25]1[CH:30]=[CH:29][C:28]([C:31]([N:33]2[CH2:42][C:41]3[CH:40]=[N:39][N:38]([CH3:43])[C:37]=3[NH:36][C:35]3[CH:44]=[C:45]([CH3:48])[CH:46]=[CH:47][C:34]2=3)=[O:32])=[CH:27][C:26]=1[F:49].Cl.Cl.[CH3:52][C:53]([CH3:63])([CH3:62])[CH2:54][CH2:55][N:56]1[CH2:61][CH2:60][NH:59][CH2:58][CH2:57]1>CN(C=O)C>[CH3:43][N:38]1[C:37]2[NH:36][C:35]3[CH:44]=[C:45]([CH3:48])[CH:46]=[CH:47][C:34]=3[N:33]([C:31]([C:28]3[CH:29]=[CH:30][C:25]([CH2:24][NH:23][C:10]([N:59]4[CH2:58][CH2:57][N:56]([CH2:55][CH2:54][C:53]([CH3:63])([CH3:62])[CH3:52])[CH2:61][CH2:60]4)=[O:11])=[C:26]([F:49])[CH:27]=3)=[O:32])[CH2:42][C:41]=2[CH:40]=[N:39]1

参加物

6

反応物 4

HCID 682631,1'-CarbonyldiimidazoleHCID 81531DiisopropylethylamineHCID 670538001-(3,3-Dimethyl-butyl)-piperazine dihydrochlorideHCID 135736009(4-Aminomethyl-3-fluoro-phenyl)-(3,6-dimethyl-4,10-dihydro-3H-2,3,4,9-tetraaza-benzo[f]azulen-9-yl)-methanone Hydrochloride

生成物 1

HCID 1361283614-(3,3-Dimethyl-butyl)-piperazine-1-carboxylic Acid 4-(3,6-dimethyl-4,10-dihydro-3H-2,3,4,9-tetraaza-benzo[f]azulene-9-carbonyl)-2-fluoro-benzylamide収率 56%

試薬・触媒・溶媒 1

HCID 6228Dimethylformamide溶媒

実験手順

DIEA (0.10 ml, 0.60 mmol) and 1,1′-carbonyldiimidazole (28 mg, 0.17 mmol) were added to a solution of (4-aminomethyl-3-fluoro-phenyl)-(3,6-dimethyl-4,10-dihydro-3H-2,3,4,9-tetraaza-benzo[f]azulen-9-yl)-methanone hydrochloride from Example E8.2 (57 mg, 0.14 mmol) in DMF (5.0 ml) and the mixture was stirred at room temperature for 4 h. 1-(3,3-Dimethyl-butyl)-piperazine dihydrochloride from Example E4 (38 mg, 0.16 mmol) was added and the mixture was stirred at room temperature for 24 h and concentrated in vacuo. The residue was dissolved in EtOAc and the resulting solution was washed with brine and concentrated in vacuo. The residue was purified by preparative HPLC (eluant; 10% methanol:90% dichloromethane) to give a white solid identified as the title compound (45 mg, 56%).

後処理

  1. stirringthe mixture was stirred at room temperature for 24 h
  2. concentrationconcentrated in vacuo
  3. dissolutionThe residue was dissolved in EtOAc
  4. washthe resulting solution was washed with brine
  5. concentrationconcentrated in vacuo
  6. customThe residue was purified by preparative HPLC (eluant; 10% methanol:90% dichloromethane)
  7. customto give a white solid

出典と根拠

ORDレコード
ord-48019a5c02f242ffb440077b9acc6384
出典データセット
uspto-grants-2012_06
特許番号
US08202858B2

反応ノート

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