Oxalyl chloride → HCID 178432323, compound

HRID 220893Notes

Reaction equation

HRID 220893 reaction equation
C(Cl)(=O)C(Cl)=O.[CH3:7][C:8]([CH3:32])([CH3:31])[CH2:9][CH2:10][N:11]1[CH2:16][CH2:15][N:14]([C:17](=[O:30])[CH2:18][CH2:19][C:20]2[CH:28]=[CH:27][C:23]([C:24]([OH:26])=O)=[CH:22][C:21]=2[CH3:29])[CH2:13][CH2:12]1.CCN(C(C)C)C(C)C.[CH3:42][C:43]1[NH:52][C:51]2[C:50]3[CH:53]=[CH:54][CH:55]=[CH:56][C:49]=3[NH:48][CH2:47][CH2:46][C:45]=2[N:44]=1>ClCCl.CN(C=O)C>[CH3:7][C:8]([CH3:32])([CH3:31])[CH2:9][CH2:10][N:11]1[CH2:16][CH2:15][N:14]([C:17](=[O:30])[CH2:18][CH2:19][C:20]2[CH:28]=[CH:27][C:23]([C:24]([N:48]3[CH2:47][CH2:46][C:45]4[N:44]=[C:43]([CH3:42])[NH:52][C:51]=4[C:50]4[CH:53]=[CH:54][CH:55]=[CH:56][C:49]3=4)=[O:26])=[CH:22][C:21]=2[CH3:29])[CH2:13][CH2:12]1

Participants

7

Reactant 4

HCID 65578Oxalyl chlorideHCID 81531DiisopropylethylamineHCID 575552774-{3-[4-(3,3-Dimethyl-butyl)-piperazin-1-yl]-3-oxo-propyl}-3-methyl-benzoic AcidHCID 178432321HCID 178432321, compound

Product 1

HCID 178432323HCID 178432323, compoundYield 28%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent

Procedure

Oxalyl chloride (0.049 ml, 0.55 mmol) was added slowly to a solution of 4-{3-[4-(3,3-dimethyl-butyl)-piperazin-1-yl]-3-oxo-propyl}-3-methyl-benzoic acid from Example E44 (100 mg, 0.28 mmol) in dichloromethane (10 ml) and few drops of DMF. The mixture was stirred for 1 h at room temperature then concentrated in vacuo and azeotroped with toluene. The residue was redissolved in dichloro-methane (10 ml) and DIEA (0.144 ml, 0.84 mmol) then 2-methyl-1,4,5,6-tetrahydro-1,3,6-triaza-benzo[e]azulene from Example E5 (55 mg, 0.28 mmol) was added. The mixture was stirred for 20 h at room temperature 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% dichloro-methane) to give a white fluffy solid identified as the title compound (42 mg, 28%).

Workup

  1. concentrationthen concentrated in vacuo
  2. customazeotroped with toluene
  3. dissolutionThe residue was redissolved in dichloro-methane (10 ml)
  4. stirringThe mixture was stirred for 20 h at room temperature
  5. washthen washed 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% dichloro-methane)
  9. customto give a white fluffy solid

Sources & evidence

ORD record
ord-135646058bc54ab39459594b044dcf39
Source dataset
uspto-grants-2012_06
Patent number
US08202858B2

Reaction notes

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