Chloroacetyl chloride → HCID 46190332, compound

HRID 2360527Notes

Reaction equation

HRID 2360527 reaction equation
[C:1]([C:5]1[CH:6]=[C:7]([NH:33][S:34]([CH3:37])(=[O:36])=[O:35])[C:8]([O:31][CH3:32])=[C:9]([NH:11][C:12]([C:14]2[N:15]([CH3:30])[C:16]3[C:21]([CH:22]=2)=[CH:20][CH:19]=[CH:18][C:17]=3[CH2:23][N:24]2[CH2:29][CH2:28][NH:27][CH2:26][CH2:25]2)=[O:13])[CH:10]=1)([CH3:4])([CH3:3])[CH3:2].C(N(CC)C(C)C)(C)C.Cl[CH2:48][C:49](Cl)=[O:50].C(=O)([O-])[O-].[K+].[K+].[CH3:58][N:59]([CH3:66])[CH:60]1[CH2:65][CH2:64][NH:63][CH2:62][CH2:61]1>ClCCl.CN(C)C=O.C(OCC)(=O)C.O>[C:1]([C:5]1[CH:6]=[C:7]([NH:33][S:34]([CH3:37])(=[O:36])=[O:35])[C:8]([O:31][CH3:32])=[C:9]([NH:11][C:12]([C:14]2[N:15]([CH3:30])[C:16]3[C:21]([CH:22]=2)=[CH:20][CH:19]=[CH:18][C:17]=3[CH2:23][N:24]2[CH2:25][CH2:26][N:27]([C:49](=[O:50])[CH2:48][N:63]3[CH2:64][CH2:65][CH:60]([N:59]([CH3:66])[CH3:58])[CH2:61][CH2:62]3)[CH2:28][CH2:29]2)=[O:13])[CH:10]=1)([CH3:4])([CH3:2])[CH3:3]

Participants

10

Reactant 5

HCID 6577Chloroacetyl chlorideHCID 11430Potassium CarbonateHCID 81531DiisopropylethylamineHCID 417391N,N-Dimethylpiperidin-4-amineHCID 59856627HCID 59856627, compound

Product 1

HCID 46190332HCID 46190332, compound

Reagents, catalysts & solvents 4

HCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
0 °C

Procedure

160 mg of 1-methyl-7-piperazin-1-ylmethyl-1H-indole-2-carboxylic acid (5-tert-butyl-3-methanesulphonylamino-2-methoxy-phenyl)-amide are dissolved in 5 ml dichloromethane, combined with 100 μL N,N-diisopropyl-ethylamine (DIEA) and cooled to 0° C. Then 30 μl of chloroacetic acid chloride are added dropwise, the mixture is heated to ambient temperature and stirred for 1 hour. The solvent is eliminated in vacuo and the residue is taken up in 2 ml N,N-dimethylformamide. Then 65 mg potassium carbonate and 55 μl 4-dimethylamino-piperidine are added successively. The mixture is stirred for 12 hours at ambient temperature, divided between water and ethyl acetate and the organic phase is washed with saturated aqueous sodium chloride solution. After drying with magnesium sulphate the solvents are eliminated in vacuo and the residue is chromatographed on silica gel (dichloromethane/(methanol/conc. ammonia 9:1) 99:1 to 85:15).

Workup

  1. temperaturethe mixture is heated to ambient temperature
  2. stirringThe mixture is stirred for 12 hours at ambient temperature
  3. washthe organic phase is washed with saturated aqueous sodium chloride solution
  4. dry with materialAfter drying with magnesium sulphate the solvents
  5. customthe residue is chromatographed on silica gel (dichloromethane/(methanol/conc. ammonia 9:1) 99:1 to 85:15)

Sources & evidence

ORD record
ord-a749023db92546d6af81201c0d2661e1
Source dataset
uspto-grants-2014_04
Patent number
US08686022B2

Reaction notes

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