Sodium Carbonate → 3-[3-(2-Ethoxy-3,5-diisopropyl-phenyl)-imidazo[1,2-a]pyridin-6-yl]-but-2-enoic acid methyl ester

HRID 1394649Notes

Reaction equation

HRID 1394649 reaction equation
[CH3:1][O:2][C:3](=[O:17])[CH:4]=[C:5]([C:7]1[CH:8]=[CH:9][C:10]2[N:11]([C:13](I)=[CH:14][N:15]=2)[CH:12]=1)[CH3:6].C(=O)([O-])[O-].[Na+].[Na+].[CH2:24]([O:26][C:27]1[C:32]([CH:33]([CH3:35])[CH3:34])=[CH:31][C:30]([CH:36]([CH3:38])[CH3:37])=[CH:29][C:28]=1B(O)O)[CH3:25]>C1(C)C=CC=CC=1.[Cl-].[Na+].O.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[CH3:1][O:2][C:3](=[O:17])[CH:4]=[C:5]([C:7]1[CH:8]=[CH:9][C:10]2[N:11]([C:13]([C:28]3[CH:29]=[C:30]([CH:36]([CH3:38])[CH3:37])[CH:31]=[C:32]([CH:33]([CH3:35])[CH3:34])[C:27]=3[O:26][CH2:24][CH3:25])=[CH:14][N:15]=2)[CH:12]=1)[CH3:6]

Participants

7

Reactant 3

HCID 10340Sodium CarbonateHCID 18504242(2-Ethoxy-3,5-diisopropylphenyl)-boronic acidHCID 692183553-(3-Iodo-imidazo[1,2-a]pyridin-6-yl)-but-2-enoic acid methyl ester

Product 1

HCID 692176403-[3-(2-Ethoxy-3,5-diisopropyl-phenyl)-imidazo[1,2-a]pyridin-6-yl]-but-2-enoic acid methyl esterYield 76.4%

Reagents, catalysts & solvents 3

HCID 178418397HCID 178418397, compoundCatalystHCID 1140TolueneSolventHCID 57417360Sodium chloride; waterSolvent

Conditions

Temperature
90 °C

Procedure

3-(3-Iodo-imidazo[1,2-a]pyridin-6-yl)-but-2-enoic acid methyl ester (168 mg, 0.49 mmol), tetrakis(triphenylphosphine)palladium(0) (57 mg, 0.05 mmol), followed by 2M sodium carbonate solution (1 ml) were added to a solution of 2-ethoxy-3,5-diisopropyl-phenyl-boronic acid (246 mg, 0.98 mmol) (see Example 5, step B) in toluene (10 mL). The reaction mixture was heated to 90° C. overnight, then poured into brine (20 mL) and extracted with ethyl acetate (2×20 mL). The organic layers were combined, dried over MgSO4 and concentrated in vacuo. The residue was purified by chromatography (chromatotron, 2μ plate, 50% ethyl acetate in hexanes) to give a 3-[3-(2-ethoxy-3,5-diisopropyl-phenyl)-imidazo[1,2-a]pyridin-6-yl]-but-2-enoic acid methyl ester as a yellow oil (157.5 mg, 76%). 1H NMR (250 MHz, CDCl3): δ 8.19 (bs, 1H), 7.75 (s, 1H), 7.68 (d, 1H, J=9.4), 7.42 (dd, 1H, J=9.4, J=1.2), 7.25 (d, 1H, J=2.5), 7.15 (d, 1H, J=2.5), 6.24 (d, 1H, J=0.62), 3.28 (s, 3H), 3.44 (m, 1H), 3.35 (q, 2H, J=8.1), 2.97 (m, 1H), 2.59 (d, 3H, J=0.62), 1.35 (s, 3H), 1.33 (s, 3H), 1.32 (s, 3H), 1.30 (s, 3H), 1.29 (t, 3H, J=8.1). MS [EI+] 421 (M+1)+.

Workup

  1. extractionextracted with ethyl acetate (2×20 mL)
  2. dry with materialdried over MgSO4
  3. concentrationconcentrated in vacuo
  4. customThe residue was purified by chromatography (chromatotron, 2μ plate, 50% ethyl acetate in hexanes)

Sources & evidence

ORD record
ord-64f79c875aca4750a3c9e66d1ed33aa5
Source dataset
uspto-grants-2008_03
Patent number
US07348359B2

Reaction notes

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