Dimethylamine → (6-Dimethylaminomethyl-imidazo[1,2-a]pyridin-3-yl)-acetic acid ethyl ester

HRID 216671Notes

Reaction equation

HRID 216671 reaction equation
[CH2:1]([O:3][C:4](=[O:17])[CH2:5][C:6]1[N:10]2[CH:11]=[C:12]([CH:15]=O)[CH:13]=[CH:14][C:9]2=[N:8][CH:7]=1)[CH3:2].[CH3:18][NH:19][CH3:20].C([BH3-])#N.[Na+].C([O-])(O)=O.[Na+]>C1COCC1.CO.C(O)(=O)C.O>[CH2:1]([O:3][C:4](=[O:17])[CH2:5][C:6]1[N:10]2[CH:11]=[C:12]([CH2:15][N:19]([CH3:20])[CH3:18])[CH:13]=[CH:14][C:9]2=[N:8][CH:7]=1)[CH3:2]

Participants

9

Reactant 4

HCID 674DimethylamineHCID 516892Sodium BicarbonateHCID 5003444Sodium cyanoborohydrideHCID 59192016Ethyl 2-(6-formylimidazo[1,2-a]pyridin-3-yl)acetate

Product 1

HCID 59192025(6-Dimethylaminomethyl-imidazo[1,2-a]pyridin-3-yl)-acetic acid ethyl esterYield 29%

Reagents, catalysts & solvents 4

HCID 176Acetic AcidSolventHCID 887MethanolSolventHCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
60 °C

Procedure

(6-Formyl-imidazo[1,2-a]pyridin-3-yl)-acetic acid ethyl ester (770 mg, 3.15 mmol) is dissolved in THF (10 ml) and treated with an excess of dimethylamine. The reaction mixture is stirred for 16 hours at room temperature in a stainless steel autoclave. A solution of sodium cyanoborohydride (229 mg, 3.46 mmol, 1.1 equiv) in MeOH (1.0 ml) and glacial acetic acid (1.1 ml) are added, and the solution is stirred for 1 hour at 60° C. The reaction mixture is diluted with water and adjusted to pH 8-9 by the addition of concentrated aqueous NaHCO3 solution. Extraction with EtOAc, washing with brine, drying over Na2SO4 and removal of solvent affords the crude reaction product. Purification via flash chromatography (EtOAc/cyclohexane 4:1, +0.2% NEt3) yields the title compound (242 mg, 29%). 1H NMR (400 MHz, CDCl3): δ=7.76-7.74 (m, 1H), 7.35 (dd, J=9.3/1.0 Hz, 1H), 7.31 (s, 1H), 6.99 (dd, J=9.1/1.7 Hz, 1H), 3.95 (q, J=7.1 Hz, 2H), 3.71 (s, 2H), 3.23 (s, 2H), 2.06 (s, 6H), 1.03 (t, J=7.1 Hz, 3H). MS (ES+): 262 (M+H)+.

Workup

  1. extractionExtraction with EtOAc
  2. washwashing with brine
  3. dry with materialdrying over Na2SO4 and removal of solvent
  4. customaffords the crude
  5. customreaction product
  6. customPurification via flash chromatography (EtOAc/cyclohexane 4:1, +0.2% NEt3)

Sources & evidence

ORD record
ord-6c64d187cc23463b98a4fc4048684e59
Source dataset
uspto-grants-2012_06
Patent number
US08193236B2

Reaction notes

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