Trifluoroacetic acid → 2-(6-Dimethylaminomethyl-imidazo[1,2-a]pyridin-3-yl)-acetamide

HRID 216670

Reaction equation

HRID 216670 reaction equation
O.[OH-].[Li+].C([O:6][C:7](=O)[CH2:8][C:9]1[N:13]2[CH:14]=[C:15]([CH2:18][N:19]([CH3:21])[CH3:20])[CH:16]=[CH:17][C:12]2=[N:11][CH:10]=1)C.FC(F)(F)C(O)=O.C(N1C=CN=C1)([N:32]1C=CN=C1)=O>O1CCOCC1.O>[CH3:20][N:19]([CH2:18][C:15]1[CH:16]=[CH:17][C:12]2[N:13]([C:9]([CH2:8][C:7]([NH2:32])=[O:6])=[CH:10][N:11]=2)[CH:14]=1)[CH3:21]

Participants

7

Reactant 4

HCID 6422Trifluoroacetic acidHCID 682631,1'-CarbonyldiimidazoleHCID 168937Lithium hydroxide, monohydrateHCID 59192025HCID 59192025, compound

Product 1

HCID 591920412-(6-Dimethylaminomethyl-imidazo[1,2-a]pyridin-3-yl)-acetamideYield 92%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 312751,4-DioxaneSolvent

Procedure

Lithium hydroxide monohydrate (55 mg, 1.31 mmol, 1.5 equiv) is added to a solution of (6-dimethylaminomethyl-imidazo[1,2-a]pyridin-3-yl)-acetic acid ethyl ester (240 mg, 0.87 mmol) in dioxane (10 ml) and water (10 ml). After 1 hour at room temperature, the reaction mixture is concentrated in vacuo. The residue is taken up in N,N-dimethylformamide (10 ml) and treated with trifluoroacetic acid (0.34 ml, 4.5 mmol, 4.5 equiv). Carbonyldiimidazole (167 mg, 0.98 mmol, 1.0 equiv) is added, and the mixture is stirred at room temperature for 1 hour. After removal of the solvent, concentrated aqueous ammonia (10 ml) is added to the activated acid. The mixture is stirred at room temperature for 30 minutes. Volatiles are removed in vacuo, and purification of the residue via flash chromatography (CH2Cl2/MeOH 7:3) affords the title compound (186 mg, 76%). 1H NMR (400 MHz, d4-MeOH): δ=8.31 (s, 1H), 7.55 (d, J=9.0 Hz, 1H), 7.49 (s, 1H), 7.35 (dd, J=9.0/1.5 Hz, 1H), 3.95 (s, 2H), 3.71 (s, 2H), 2.42 (s, 6H). MS (ES+): 233 (M+H)+.

Workup

  1. concentrationthe reaction mixture is concentrated in vacuo
  2. customAfter removal of the solvent, concentrated aqueous ammonia (10 ml)
  3. additionis added to the activated acid
  4. stirringThe mixture is stirred at room temperature for 30 minutes
  5. customVolatiles are removed in vacuo, and purification of the residue via flash chromatography (CH2Cl2/MeOH 7:3)

Sources & evidence

ORD record
ord-f224263e6e4e447584dae6fd3a0c2bc1
Source dataset
uspto-grants-2012_06
Patent number
US08193236B2

Linked notes

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