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

HRID 220924Notes

Reaction equation

HRID 220924 reaction equation
C(Cl)(=O)C(Cl)=O.[CH3:7][N:8]1[C:17]2[N:16]([CH3:18])[C:15]3[CH:19]=[CH:20][CH:21]=[CH:22][C:14]=3[N:13]([C:23]([C:25]3[CH:30]=[CH:29][C:28]([CH2:31][CH2:32][C:33]([OH:35])=O)=[C:27]([CH3:36])[CH:26]=3)=[O:24])[CH2:12][C:11]=2[CH:10]=[N:9]1.Cl.Cl.[CH3:39][C:40]([CH3:50])([CH3:49])[CH2:41][CH2:42][N:43]1[CH2:48][CH2:47][NH:46][CH2:45][CH2:44]1.CCN(C(C)C)C(C)C>ClCCl.CN(C=O)C>[CH3:39][C:40]([CH3:50])([CH3:49])[CH2:41][CH2:42][N:43]1[CH2:44][CH2:45][N:46]([C:33](=[O:35])[CH2:32][CH2:31][C:28]2[CH:29]=[CH:30][C:25]([C:23]([N:13]3[CH2:12][C:11]4[CH:10]=[N:9][N:8]([CH3:7])[C:17]=4[N:16]([CH3:18])[C:15]4[CH:19]=[CH:20][CH:21]=[CH:22][C:14]3=4)=[O:24])=[CH:26][C:27]=2[CH3:36])[CH2:47][CH2:48]1

Participants

7

Reactant 4

HCID 65578Oxalyl chlorideHCID 81531DiisopropylethylamineHCID 575553673-[4-(3,4-Dimethyl-4,10-dihydro-3H-2,3,4,9-tetraaza-benzo[f]azulene-9-carbonyl)-2-methyl-phenyl]-propionic AcidHCID 670538001-(3,3-Dimethyl-butyl)-piperazine dihydrochloride

Product 1

HCID 575553321-[4-(3,3-Dimethyl-butyl)-piperazin-1-yl]-3-[4-(3,4-dimethyl-4,10-dihydro-3H-2,3,4,9-tetraaza-benzo[f]azulene-9-carbonyl)-2-methyl-phenyl]-propan-1-oneYield 65%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideCatalystHCID 6344DichloromethaneSolvent

Procedure

Oxalyl chloride (0.018 ml, 0.20 mmol) was added to a solution of 3-[4-(3,4-dimethyl-4,10-dihydro-3H-2,3,4,9-tetraaza-benzo[f]azulene-9-carbonyl)-2-methyl-phenyl]-propionic acid from Example E80.2 (40 mg, 0.10 mmol) in dichloromethane (5 ml) and a few drops of DMF. The mixture was stirred for 1 h at room temperature, concentrated in vacuo and azeotroped with toluene. The residue was dissolved in dichloromethane (5 ml) and 1-(3,3-dimethyl-butyl)-piperazine dihydrochloride from Example E4 (30 mg, 0.12 mmol) and DIEA (0.052 ml, 0.30 mmol) were added. The mixture was stirred for 20 h at room temperature, 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 (36 mg, 65%).

Workup

  1. concentrationconcentrated in vacuo
  2. customazeotroped with toluene
  3. dissolutionThe residue was dissolved in dichloromethane (5 ml)
  4. stirringThe mixture was stirred for 20 h at room temperature
  5. washwashed with saturated NaHCO3
  6. dry with materialbrine, dried
  7. concentrationconcentrated in vacuo
  8. customThe residue was purified by preparative HPLC (eluant; 0.5% 35% ammonia:9.5% methanol:90% dichloromethane)
  9. customto give a white powder

Sources & evidence

ORD record
ord-77442b585ddf4a65aa369b7ba39b0573
Source dataset
uspto-grants-2012_06
Patent number
US08202858B2

Reaction notes

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