N-methyl-2-pyrrolidone → HCID 57384605, compound

HRID 706684Notes

Reaction equation

HRID 706684 reaction equation
[CH3:1][N:2]1[CH2:7][CH2:6][N:5]([CH2:8][CH2:9][O:10][C:11]2[CH:16]=[CH:15][N:14]3[C:17]([C:20]([O-])=[O:21])=[CH:18][N:19]=[C:13]3[CH:12]=2)[CH2:4][CH2:3]1.[Li+].CN1C(=O)CCC1.ClC1C=C(Cl)C=C(Cl)C=1C(Cl)=O.[NH2:43][C:44]1[CH:52]=[CH:51][CH:50]=[C:49]2[C:45]=1[CH:46]=[N:47][N:48]2[CH2:53][C:54]1[CH:55]=[C:56]([CH:59]=[CH:60][CH:61]=1)[C:57]#[N:58]>CCOC(C)=O.C([O-])(O)=O.[Na+]>[C:57]([C:56]1[CH:55]=[C:54]([CH:61]=[CH:60][CH:59]=1)[CH2:53][N:48]1[C:49]2[C:45](=[C:44]([NH:43][C:20]([C:17]3[N:14]4[CH:15]=[CH:16][C:11]([O:10][CH2:9][CH2:8][N:5]5[CH2:6][CH2:7][N:2]([CH3:1])[CH2:3][CH2:4]5)=[CH:12][C:13]4=[N:19][CH:18]=3)=[O:21])[CH:52]=[CH:51][CH:50]=2)[CH:46]=[N:47]1)#[N:58]

Participants

7

Reactant 4

HCID 13387N-methyl-2-pyrrolidone2×HCID 27337032,4,6-Trichlorobenzoyl chlorideHCID 67252742Lithium 7-(2-(4-methylpiperazin-1-yl)ethoxy)imidazo[1,2-a]pyridine-3-carboxylateHCID 67976137HCID 67976137, compound

Product 1

HCID 57384605HCID 57384605, compoundYield 49.1%

Reagents, catalysts & solvents 2

HCID 8857Ethyl AcetateSolventHCID 516892Sodium BicarbonateSolvent

Procedure

To a vial was added lithium 7-(2-(4-methylpiperazin-1-yl)ethoxy)imidazo[1,2-a]pyridine-3-carboxylate (0.187 g, 0.544 mmol) and NMP (3.0 mL), and the mixture was warmed until homogeneous and then cooled to ambient temperature. 2,4,6-Trichlorobenzoyl chloride (0.0793 mL, 0.507 mmol) was added and the dark solution was stirred at ambient temperature for 0.5 hours. 3-((4-Amino-1H-indazol-1-yl)methyl)benzonitrile (0.090 g, 0.362 mmol) was added as a NMP solution (3.0 mL) and the mixture was heated to 75° C. with stirring for 3 hours. The reaction was equilibrated to ambient temperature and the mixture was diluted with EtOAc (30 mL) and saturated aqueous NaHCO3 (10 mL). The organic layer was washed with brine, dried over Na2SO4, concentrated and purified by column chromatography (15% MeOH/CH2Cl2 adding 1% 7N NH3/MeOH). The red/brown solid was slurried in Et2O and then filtered, and the isolated solid was washed with Et2O providing a pale red/brown solid that was dried under vacuum to provide 0.095 g (42%) of the desired product. MS (ES+APCI) m/z=535 (M+H).

Workup

  1. temperaturethe mixture was warmed until homogeneous and
  2. temperaturethe mixture was heated to 75° C.
  3. stirringwith stirring for 3 hours
  4. customwas equilibrated to ambient temperature
  5. washThe organic layer was washed with brine
  6. dry with materialdried over Na2SO4
  7. concentrationconcentrated
  8. custompurified by column chromatography (15% MeOH/CH2Cl2 adding 1% 7N NH3/MeOH)
  9. filtrationfiltered
  10. washthe isolated solid was washed with Et2O providing a pale red/brown solid that
  11. customwas dried under vacuum

Sources & evidence

ORD record
ord-1ee52405923341639af22addb179a542
Source dataset
uspto-grants-2015_11
Patent number
US09174981B2

Reaction notes

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