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)-cyclohexylmethyl]-amide

HRID 220810Notes

Reaction equation

HRID 220810 reaction equation
CCN(C(C)C)C(C)C.[C:10](N1C=CN=C1)(N1C=CN=C1)=[O:11].Cl.[NH2:23][CH2:24][CH:25]1[CH2:30][CH2:29][CH: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])[CH2:27][CH2:26]1.Cl.Cl.[CH3:51][C:52]([CH3:62])([CH3:61])[CH2:53][CH2:54][N:55]1[CH2:60][CH2:59][NH:58][CH2:57][CH2:56]1>CN(C=O)C.CCOC(C)=O>[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]([CH:28]3[CH2:29][CH2:30][CH:25]([CH2:24][NH:23][C:10]([N:58]4[CH2:57][CH2:56][N:55]([CH2:54][CH2:53][C:52]([CH3:62])([CH3:61])[CH3:51])[CH2:60][CH2:59]4)=[O:11])[CH2:26][CH2:27]3)=[O:32])[CH2:42][C:41]=2[CH:40]=[N:39]1

Participants

7

Reactant 4

HCID 682631,1'-CarbonyldiimidazoleHCID 81531DiisopropylethylamineHCID 670538001-(3,3-Dimethyl-butyl)-piperazine dihydrochlorideHCID 136346633(4-Aminomethyl-cyclohexyl)-(3,6-dimethyl-4,10-dihydro-3H-2,3,4,9-tetraaza-benzo[f]azulen-9-yl)-methanone hydrochloride

Product 1

HCID 1354759954-(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)-cyclohexylmethyl]-amideYield 29.1%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

DIEA (0.30 ml, 1.7 mmol) and 1,1′-carbonyldiimidazole (39 mg, 0.24 mmol) were added to a solution of (4-aminomethyl-cyclohexyl)-(3,6-dimethyl-4,10-dihydro-3H-2,3,4,9-tetraaza-benzo[f]azulen-9-yl)-methanone hydro-chloride (Compound number 149) (78 mg, 0.20 mmol) in DMF (4.0 ml) and the mixture was stirred at room temperature for 2 h. 1-(3,3-Dimethyl-butyl)-piperazine dihydrochloride from Example E4 (56 mg, 0.23 mmol) was added and the mixture was stirred at room temperature for 18 h. The mixture was diluted with EtOAc, washed with brine, dried and concentrated in vacuo. The residue was purified by preparative HPLC (eluant; 10% methanol:90% di-chloromethane) to give a white solid identified as the title compound (32 mg, 29%).

Workup

  1. stirringthe mixture was stirred at room temperature for 18 h
  2. washwashed with brine
  3. customdried
  4. concentrationconcentrated in vacuo
  5. customThe residue was purified by preparative HPLC (eluant; 10% methanol:90% di-chloromethane)
  6. customto give a white solid

Sources & evidence

ORD record
ord-1ee9691b6de249228c0463692443256e
Source dataset
uspto-grants-2012_06
Patent number
US08202858B2

Reaction notes

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