Sodium Iodide → 5-amino-6-chloro-N-{[1-(3,3-dimethyl-2-oxobutyl)piperidin-4-yl]methyl}-2-ethylimidazo[1,2-a]pyridine-8-carboxamide

HRID 965802Notes

Reaction equation

HRID 965802 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].Br[CH2:25][C:26](=[O:31])[C:27]([CH3:30])([CH3:29])[CH3:28].[I-].[Na+].C(N(CC)CC)C>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][C:26](=[O:31])[C:27]([CH3:30])([CH3:29])[CH3:28])[CH2:19][CH2:18]2)=[O:14])=[CH:4][C:3]=1[Cl:23]

Participants

6

Reactant 4

HCID 5238Sodium IodideHCID 8471TriethylamineHCID 21642BromopinacoloneHCID 99496125-amino-6-chloro-2-ethyl-N-(piperidin-4-ylmethyl)imidazo[1,2-a]pyridine-8-carboxamide

Product 1

HCID 223132735-amino-6-chloro-N-{[1-(3,3-dimethyl-2-oxobutyl)piperidin-4-yl]methyl}-2-ethylimidazo[1,2-a]pyridine-8-carboxamideYield 32%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
70 °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, 150 mg, 0.446 mmol) and 1-bromo-3,3-dimethylbutan-2-one (72 μL, 0.670 mmol) in N,N-dimethylformamide (4.4 mL) were added sodium iodide (67 mg, 0.670 mmol) and triethylamine (0.156 mL, 1.12 mmol). The reaction mixture was stirred at 70° C. for 76 h. After removal of solvent, the residue was dissolved in ethyl acetate (100 mL), and washed with aqueous sodium bicarbonate (5 mL) and brine. The organic layer was dried over magnesium sulfate and concentrated in vacuo. Flash column chromatography (NH-silica gel) of the residue eluting with hexane/ethyl acetate (9:1 to 1:1) afforded a pale brown solid, which was recrystallized from ethyl acetate to afford 62 mg (32%) of the title compound as off-white solid.

Workup

  1. customAfter removal of solvent
  2. dissolutionthe residue was dissolved in ethyl acetate (100 mL)
  3. washwashed with aqueous sodium bicarbonate (5 mL) and brine
  4. dry with materialThe organic layer was dried over magnesium sulfate
  5. concentrationconcentrated in vacuo
  6. washFlash column chromatography (NH-silica gel) of the residue eluting with hexane/ethyl acetate (9:1 to 1:1)
  7. customafforded a pale brown solid, which
  8. customwas recrystallized from ethyl acetate

Sources & evidence

ORD record
ord-ad3ee26c4892493db315e9af4385385f
Source dataset
uspto-grants-2005_10
Patent number
US06951867B2

Reaction notes

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