Diisopropylethylamine → 1-[4-(3,3-Dimethyl-butyl)-piperazin-1-yl]-4-[2-methyl-4-(3-methyl-4,10-dihydro-3H-2,3,4,9-tetraaza-benzo[f]azulene-9-carbonyl)-phenyl]-butan-1-one

HRID 220887Notes

Reaction equation

HRID 220887 reaction equation
[CH3:1][C:2]([CH3:27])([CH3:26])[CH2:3][CH2:4][N:5]1[CH2:10][CH2:9][N:8]([C:11](=[O:25])[CH2:12][CH2:13][CH2:14][C:15]2[CH:23]=[CH:22][C:18]([C:19](O)=[O:20])=[CH:17][C:16]=2[CH3:24])[CH2:7][CH2:6]1.[CH3:28][N:29]1[C:38]2[NH:37][C:36]3[CH:39]=[CH:40][CH:41]=[CH:42][C:35]=3[NH:34][CH2:33][C:32]=2[CH:31]=[N:30]1.CCN(C(C)C)C(C)C>ClCCl.CN(C1C=CN=CC=1)C>[CH3:1][C:2]([CH3:27])([CH3:26])[CH2:3][CH2:4][N:5]1[CH2:10][CH2:9][N:8]([C:11](=[O:25])[CH2:12][CH2:13][CH2:14][C:15]2[CH:23]=[CH:22][C:18]([C:19]([N:34]3[CH2:33][C:32]4[CH:31]=[N:30][N:29]([CH3:28])[C:38]=4[NH:37][C:36]4[CH:39]=[CH:40][CH:41]=[CH:42][C:35]3=4)=[O:20])=[CH:17][C:16]=2[CH3:24])[CH2:7][CH2:6]1

Participants

6

Reactant 3

HCID 81531DiisopropylethylamineHCID 575552274-{4-[4-(3,3-Dimethyl-butyl)-piperazin-1-yl]-4-oxo-butyl}-3-methyl-benzoic AcidHCID 1357419771-Methyl-1,4,5,10-tetrahydrobenzo[b]pyrazolo[3,4-e][1,4]diazepine

Product 1

HCID 1357360131-[4-(3,3-Dimethyl-butyl)-piperazin-1-yl]-4-[2-methyl-4-(3-methyl-4,10-dihydro-3H-2,3,4,9-tetraaza-benzo[f]azulene-9-carbonyl)-phenyl]-butan-1-oneYield 5%

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6344DichloromethaneSolvent

Procedure

4-{4-[4-(3,3-Dimethyl-butyl)-piperazin-1-yl]-4-oxo-butyl}-3-methyl-benzoic acid from Example E43 (139 mg, 0.37 mmol) and 3-methyl-3,4,9,10-tetrahydro-2,3,4,9-tetraaza-benzo[f]azulene from Example E11 (75 mg, 0.37 mmol) were dissolved in dichloromethane (5 ml) and DIEA (0.195 ml, 1.11 mmol). WSCD (93 mg, 0.48 mmol) and DMAP (9 mg, 0.07 mmol) were added and the mixture was heated at reflux for 3 days, then washed with saturated NaHCO3 then brine, dried and concentrated in vacuo. The residue was purified by preparative HPLC (eluant; 0.5% 35% ammonia:9.5% methanol:90% dichloromethane) to give a white powder identified as the title compound (11 mg, 5%).

Workup

  1. temperaturethe mixture was heated
  2. temperatureat reflux for 3 days
  3. washwashed with saturated NaHCO3
  4. dry with materialbrine, dried
  5. concentrationconcentrated in vacuo
  6. customThe residue was purified by preparative HPLC (eluant; 0.5% 35% ammonia:9.5% methanol:90% dichloromethane)
  7. customto give a white powder

Sources & evidence

ORD record
ord-f17782379f854bac821e59f160a58cc6
Source dataset
uspto-grants-2012_06
Patent number
US08202858B2

Reaction notes

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