5-amino-6-chloro-2-ethyl-N-(piperidin-4-ylmethyl)imidazo[1,2-a]pyridine-8-carboxamide → 5-amino-6-chloro-2-ethyl-N-{[1-(4-hydroxy-3,3-dimethyl-2-oxobutyl)piperidin-4-yl]methyl}imidazo[1,2-a]pyridine-8-carboxamide

HRID 965804Notes

Reaction equation

HRID 965804 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].FC(F)(F)C([O:28][CH2:29][C:30]([CH3:36])([CH3:35])[C:31](=[O:34])[CH2:32]Br)=O>CO>[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]([CH2:32][C:31](=[O:34])[C:30]([CH3:36])([CH3:35])[CH2:29][OH:28])[CH2:19][CH2:18]2)=[O:14])=[CH:4][C:3]=1[Cl:23]

Participants

4

Reactant 2

HCID 99496125-amino-6-chloro-2-ethyl-N-(piperidin-4-ylmethyl)imidazo[1,2-a]pyridine-8-carboxamideHCID 859569444-Bromo-2,2-dimethyl-3-oxobutyl trifluoroacetate

Product 1

HCID 99811725-amino-6-chloro-2-ethyl-N-{[1-(4-hydroxy-3,3-dimethyl-2-oxobutyl)piperidin-4-yl]methyl}imidazo[1,2-a]pyridine-8-carboxamideYield 25%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

A mixture of 5-amino-6-chloro-2-ethyl-N-(piperidin-4-ylmethyl)imidazo[1,2-a]-pyridine-8-carboxamide (Example 4, step 4, 530 mg, 1.57 mmol) and 4-bromo-2,2-dimethyl-3-oxobutyl trifluoroacetate (Example 6, step 1, 777 mg, 2.67 mmol) in methanol (15 mL) was stirred at room temperature for 5 days. The reaction mixture was concentrated in vacuo. The residue was basified with aqueous potassium carbonate (20 mL) and extracted with dichloromethane (3×30 mL). The combined extract was washed with brine, dried over magnesium sulfate, and evaporated. Flash column chromatography (NH-silica gel) of the residue eluting with dichloromethane/methanol (200:1 to 50:1) afforded a white solid. This was recrystallized from ethanol to afford 173 mg (25%) of the title compound as a white solid.

Workup

  1. concentrationThe reaction mixture was concentrated in vacuo
  2. extractionextracted with dichloromethane (3×30 mL)
  3. extractionThe combined extract
  4. washwas washed with brine
  5. dry with materialdried over magnesium sulfate
  6. customevaporated
  7. washFlash column chromatography (NH-silica gel) of the residue eluting with dichloromethane/methanol (200:1 to 50:1)
  8. customafforded a white solid
  9. customThis was recrystallized from ethanol

Sources & evidence

ORD record
ord-0df8d1a3d85f4409be1cdc023e34d06e
Source dataset
uspto-grants-2005_10
Patent number
US06951867B2

Reaction notes

Loading…