Sodium Iodide → 5-AMINO-6-CHLORO-2-ETHYL-N-{[1-(3-MORPHOLIN-4-YL-3-OXOPROPYL)PIPERIDIN-4-YL]METHYL}IMIDAZO[1,2-a]PYRIDINE-8-CARBOXAMIDE

HRID 965806Notes

Reaction equation

HRID 965806 reaction equation
[NH2:1][C:2]1[N:7]2[CH:8]=[C:9]([CH2:11][CH3:12])[N:10]=[C:6]2[C:5]([C:13]([NH:15][CH2:16][CH:17]2[CH2:22][CH2:21][NH:20][CH2:19][CH2:18]2)=[O:14])=[CH:4][C:3]=1[Cl:23].Cl[CH2:25][CH2:26][C:27]([N:29]1[CH2:34][CH2:33][O:32][CH2:31][CH2:30]1)=[O:28].C(=O)([O-])[O-].[K+].[K+].[I-].[Na+]>CN(C)C=O>[NH2:1][C:2]1[N:7]2[CH:8]=[C:9]([CH2:11][CH3:12])[N:10]=[C:6]2[C:5]([C:13]([NH:15][CH2:16][CH:17]2[CH2:22][CH2:21][N:20]([CH2:25][CH2:26][C:27]([N:29]3[CH2:34][CH2:33][O:32][CH2:31][CH2:30]3)=[O:28])[CH2:19][CH2:18]2)=[O:14])=[CH:4][C:3]=1[Cl:23]

Participants

6

Reactant 4

HCID 5238Sodium IodideHCID 11430Potassium CarbonateHCID 5320543-Chloro-1-(morpholin-4-yl)propan-1-oneHCID 99496125-amino-6-chloro-2-ethyl-N-(piperidin-4-ylmethyl)imidazo[1,2-a]pyridine-8-carboxamide

Product 1

HCID 100965595-AMINO-6-CHLORO-2-ETHYL-N-{[1-(3-MORPHOLIN-4-YL-3-OXOPROPYL)PIPERIDIN-4-YL]METHYL}IMIDAZO[1,2-a]PYRIDINE-8-CARBOXAMIDEYield 63.2%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
90 °C

Procedure

To a stirred mixture of 5-amino-6-chloro-2-ethyl-N-(piperidin-4-ylmethyl)imidazo[1,2-a]pyridine-8-carboxamide (Example 4, Step 4, 400 mg, 1.19 mmol) and 4-(3-chloro-propanoyl)morpholine (G. Mattalia,; C. Serafini; U. Bucciarelli, Farmaco, Ed. Sci., 1976, 31, 457-67., 529 mg, 2.98 mmol) in N,N-dimethylformamide (5 mL) were added potassium carbonate (576 mg, 4.17 mmol) and sodium iodide (446 mg, 2.98 mmol). After stirring at 90° C. for 48 h, the reaction mixture was cooled to room temperature. The mixture was evaporated and the obtained residue was partitioned between dichloromethane (30 mL) and water (20 mL). The mixture was extracted with dichloromethane (2×30 mL). The combined extract was washed with brine, dried over magnesium sulfate, and concentrated in vacuo. Flash column chromatography (NH-silica gel) of the residue eluting with dichloromethane/methanol (100:1 to 20:1) afforded a yellow amorphous powder, which was crystallized from ethyl acetate/ethanol to give 359 mg (63%) of the title compound as a pale brown solid.

Workup

  1. temperaturethe reaction mixture was cooled to room temperature
  2. customThe mixture was evaporated
  3. customthe obtained residue was partitioned between dichloromethane (30 mL) and water (20 mL)
  4. extractionThe mixture was extracted with dichloromethane (2×30 mL)
  5. extractionThe combined extract
  6. washwas washed with brine
  7. dry with materialdried over magnesium sulfate
  8. concentrationconcentrated in vacuo
  9. washFlash column chromatography (NH-silica gel) of the residue eluting with dichloromethane/methanol (100:1 to 20:1)
  10. customafforded a yellow amorphous powder, which
  11. customwas crystallized from ethyl acetate/ethanol

Sources & evidence

ORD record
ord-2bbb9a8011e743c69c34d30bb829c1fb
Source dataset
uspto-grants-2005_10
Patent number
US06951867B2

Reaction notes

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