Water → HCID 46190561, compound

HRID 2360525Notes

Reaction equation

HRID 2360525 reaction equation
[CH3:1][N:2]1[CH2:7][CH2:6][CH2:5][CH:4]([C:8]([OH:10])=O)[CH2:3]1.C(N1C=CN=C1)(N1C=CN=C1)=O.[C:23]([C:27]1[CH:28]=[C:29]([NH:55][S:56]([CH3:59])(=[O:58])=[O:57])[C:30]([O:53][CH3:54])=[C:31]([NH:33][C:34]([C:36]2[N:37]([CH3:52])[C:38]3[C:43]([CH:44]=2)=[CH:42][CH:41]=[CH:40][C:39]=3[CH2:45][N:46]2[CH2:51][CH2:50][NH:49][CH2:48][CH2:47]2)=[O:35])[CH:32]=1)([CH3:26])([CH3:25])[CH3:24].O>O1CCCC1.C(OCC)(=O)C>[C:23]([C:27]1[CH:28]=[C:29]([NH:55][S:56]([CH3:59])(=[O:58])=[O:57])[C:30]([O:53][CH3:54])=[C:31]([NH:33][C:34]([C:36]2[N:37]([CH3:52])[C:38]3[C:43]([CH:44]=2)=[CH:42][CH:41]=[CH:40][C:39]=3[CH2:45][N:46]2[CH2:47][CH2:48][N:49]([C:8]([CH:4]3[CH2:5][CH2:6][CH2:7][N:2]([CH3:1])[CH2:3]3)=[O:10])[CH2:50][CH2:51]2)=[O:35])[CH:32]=1)([CH3:26])([CH3:24])[CH3:25]

Participants

7

Reactant 4

HCID 962WaterHCID 682631,1'-Carbonyldiimidazole2×HCID 27369371-methylpiperidine-3-carboxylic Acid2×HCID 59856627HCID 59856627, compound

Product 1

HCID 46190561HCID 46190561, compound

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolvent2×HCID 8857Ethyl AcetateSolvent

Conditions

Temperature
50 °C

Procedure

61 mg 1-methyl-piperidine-3-carboxylic acid are dissolved in 1 ml of tetrahydrofuran, combined with 69 mg carbonyldiimidazole and stirred for 20 minutes at 50° C. The mixture is left to cool to ambient temperature, 150 mg 1-methyl-7-piperazin-1-ylmethyl-1H-indole-2-carboxylic acid (5-tert-butyl-3-methanesulphonylamino-2-methoxy-phenyl)-amide are added and then the mixture is stirred for 12 hours at ambient temperature. Then a further 122 mg of 1-methyl-piperidine-3-carboxylic acid in 2 ml of tetrahydrofuran are combined with 138 mg carbonyldiimidazole, the mixture is stirred for 20 minutes at 50° C. and this solution is added to the reaction mixture. It is stirred for 2 hours at 50° C., then divided between water and ethyl acetate, the organic phase is washed with saturated aqueous sodium chloride solution, dried with magnesium sulphate and the solvents are eliminated in vacuo. The residue is chromatographed on silica gel with dichloromethane/(methanol/ammonia 9:1) 99:1 to 90:10. The product thus obtained is purified by preparative HPLC (HPLC method 3).

Workup

  1. waitThe mixture is left
  2. temperatureto cool to ambient temperature
  3. stirringthe mixture is stirred for 12 hours at ambient temperature
  4. stirringthe mixture is stirred for 20 minutes at 50° C.
  5. additionthis solution is added to the reaction mixture
  6. stirringIt is stirred for 2 hours at 50° C.
  7. washthe organic phase is washed with saturated aqueous sodium chloride solution
  8. dry with materialdried with magnesium sulphate
  9. customThe residue is chromatographed on silica gel with dichloromethane/(methanol/ammonia 9:1) 99:1 to 90:10
  10. customThe product thus obtained
  11. customis purified by preparative HPLC (HPLC method 3)

Sources & evidence

ORD record
ord-e332837f93b640369b1b0769b3956362
Source dataset
uspto-grants-2014_04
Patent number
US08686022B2

Reaction notes

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