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 220790노트

반응식

HRID 220790 반응식
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

참가 물질

6

반응물 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

생성물 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-benzylamide수율 56%

시약·촉매·용매 1

HCID 6228Dimethylformamide용매

실험 절차

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%).

후처리

  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

출처 및 근거

ORD 기록
ord-48019a5c02f242ffb440077b9acc6384
출처 데이터셋
uspto-grants-2012_06
특허 번호
US08202858B2

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