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 220790Notes

Reaction equation

HRID 220790 reaction equation
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

Participants

6

Reactant 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

Product 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-benzylamideYield 56%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

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%).

Workup

  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

Sources & evidence

ORD record
ord-48019a5c02f242ffb440077b9acc6384
Source dataset
uspto-grants-2012_06
Patent number
US08202858B2

Reaction notes

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