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

HRID 220933Notes

Reaction equation

HRID 220933 reaction equation
[CH:1]1([CH2:5][N:6]2[CH2:11][CH2:10][N:9]([C:12](=[O:24])[CH2:13][C:14]3[CH:22]=[CH:21][C:17]([C:18](O)=[O:19])=[CH:16][C:15]=3[CH3:23])[CH2:8][CH2:7]2)[CH2:4][CH2:3][CH2:2]1.[CH3:25][N:26]1[C:35]2[NH:34][C:33]3[CH:36]=[CH:37][CH:38]=[CH:39][C:32]=3[NH:31][CH2:30][C:29]=2[CH:28]=[N:27]1.CCN(C(C)C)C(C)C>CN(C1C=CN=CC=1)C.ClCCl>[CH:1]1([CH2:5][N:6]2[CH2:7][CH2:8][N:9]([C:12](=[O:24])[CH2:13][C:14]3[CH:22]=[CH:21][C:17]([C:18]([N:31]4[CH2:30][C:29]5[CH:28]=[N:27][N:26]([CH3:25])[C:35]=5[NH:34][C:33]5[CH:36]=[CH:37][CH:38]=[CH:39][C:32]4=5)=[O:19])=[CH:16][C:15]=3[CH3:23])[CH2:10][CH2:11]2)[CH2:4][CH2:3][CH2:2]1

Participants

6

Reactant 3

HCID 81531DiisopropylethylamineHCID 575554124-[2-(4-Cyclobutylmethyl-piperazin-1-yl)-2-oxo-ethyl]-3-methyl-benzoic AcidHCID 1357419771-Methyl-1,4,5,10-tetrahydrobenzo[b]pyrazolo[3,4-e][1,4]diazepine

Product 1

HCID 1361284321-(4-Cyclobutylmethyl-piperazin-1-yl)-2-[2-methyl-4-(3-methyl-4,10-dihydro-3H-2,3,4,9-tetraaza-benzo[f]azulene-9-carbonyl)-phenyl]-ethanoneYield 32%

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6344DichloromethaneSolvent

Procedure

WSCD (76 mg, 0.39 mmol) and DMAP (7 mg, 0.06 mmol) were added to a solution of 4-[2-(4-cyclobutylmethyl-piperazin-1-yl)-2-oxo-ethyl]-3-methyl-benzoic acid from Example E85.2 (100 mg, 0.30 mmol) and 3-methyl-3,4,9,10-tetrahydro-2,3,4,9-tetraaza-benzo[f]azulene from Example E11 (61 mg, 0.30 mmol) in dichloromethane (20 ml) and DIEA (0.16 ml, 0.91 mmol). The mixture was heated at reflux for 20 h and concentrated in vacuo. The residue was purified by flash chromatography on silica gel (eluant; 4% methanol:96% dichloromethane to 6% methanol:94% dichloromethane to 1% 35% ammonia:7% methanol:92% dichloromethane) to give an off-white solid identified as the title compound (50 mg, 32%).

Workup

  1. temperatureThe mixture was heated
  2. temperatureat reflux for 20 h
  3. concentrationconcentrated in vacuo
  4. customThe residue was purified by flash chromatography on silica gel (eluant; 4% methanol:96% dichloromethane to 6% methanol:94% dichloromethane to 1% 35% ammonia:7% methanol:92% dichloromethane)
  5. customto give an off-white solid

Sources & evidence

ORD record
ord-b445d61964c849e69973f2d93fdf60a0
Source dataset
uspto-grants-2012_06
Patent number
US08202858B2

Reaction notes

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