Hydrochloric Acid → 3-Imidazo[1,2-a]pyridin-6-yl-but-2-enoic acid methyl ester

HRID 1394647Notes

Reaction equation

HRID 1394647 reaction equation
CO[CH:3](OC)[CH2:4]Br.Cl.C(=O)(O)[O-].[Na+].[CH3:14][O:15][C:16](=[O:27])[CH:17]=[C:18]([C:20]1[CH:21]=[N:22][C:23]([NH2:26])=[CH:24][CH:25]=1)[CH3:19]>O>[CH3:14][O:15][C:16](=[O:27])[CH:17]=[C:18]([C:20]1[CH:25]=[CH:24][C:23]2[N:22]([CH:3]=[CH:4][N:26]=2)[CH:21]=1)[CH3:19]

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 816722-Bromo-1,1-dimethoxyethaneHCID 516892Sodium BicarbonateHCID 692203773-(2-Amino-pyridin-5-yl)-but-2-enoic Acid Methyl Ester

Product 1

HCID 692181443-Imidazo[1,2-a]pyridin-6-yl-but-2-enoic acid methyl ester

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Procedure

Bromoacetaldehyde dimethyl acetal (0.692 mL, 5.85 mmol) was refluxed in a solution of water (10 mL) and concentrated HCl (0.1 mL) for 30 min. The reaction was cooled to ambient temperature, and sodium bicarbonate (629 mg, 7.49 mmol) was added in several portions. After the addition was complete, 3-(6-amino-pyridin-3-yl)-but-2-enoic acid methyl ester (900 mg, 4.68 mmol) was added, and the reaction stirred overnight. During this time, the reaction became homogenous. After extracting the reaction mixture with ethyl acetate (3×20 mL), the organic layers were combined, dried over MgSO4 and concentrated in vacuo. The residue was purified by chromatography (chromatotron, 4μ plate, 50% ethyl acetate in hexanes) to yield 3-imidazo[1,2-a]pyridin-6-yl-but-2-enoic acid methyl ester as an off white solid (223.3 mg, 22%). 1H NMR (250 MHz, CDCl3): δ 8.32 (bs, 1H), 7.58-7.70 (m, 3H), 7.35 (dd, 1H, J=7.5, J=3.1), 6.24 (d, 1H, J=0.62), 3.31 (s, 3H), 2.64 (d, 3H, J=0.62). MS [EI+] 217 (M+H)+.

Workup

  1. additionAfter the addition
  2. extractionAfter extracting the reaction mixture with ethyl acetate (3×20 mL)
  3. dry with materialdried over MgSO4
  4. concentrationconcentrated in vacuo
  5. customThe residue was purified by chromatography (chromatotron, 4μ plate, 50% ethyl acetate in hexanes)

Sources & evidence

ORD record
ord-57348b2047664a2a97c293a76ce56a1b
Source dataset
uspto-grants-2008_03
Patent number
US07348359B2

Reaction notes

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