Sodium Carbonate → 3-[3-(2-Cyanothien-3-yl)phenyl]imidazo[1,2-alpha]pyridine-7-carboxylic acid methyl ester

HRID 985532Notes

Reaction equation

HRID 985532 reaction equation
[CH3:1][O:2][C:3]([C:5]1[CH:10]=[CH:9][N:8]2[C:11](Br)=[CH:12][N:13]=[C:7]2[CH:6]=1)=[O:4].CC1(C)C(C)(C)OB([C:23]2[CH:24]=[C:25]([C:29]3[CH:33]=[CH:32][S:31][C:30]=3[C:34]#[N:35])[CH:26]=[CH:27][CH:28]=2)O1.C(=O)([O-])[O-].[Na+].[Na+]>COCCOC.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>[NH3:8].[CH3:1][O:2][C:3]([C:5]1[CH:10]=[CH:9][N:8]2[C:11]([C:27]3[CH:28]=[CH:23][CH:24]=[C:25]([C:29]4[CH:33]=[CH:32][S:31][C:30]=4[C:34]#[N:35])[CH:26]=3)=[CH:12][N:13]=[C:7]2[CH:6]=1)=[O:4]

Participants

7

Reactant 3

HCID 10340Sodium CarbonateHCID 225070883-[3-(4,4,5,5-Tetramethyl-[1,3,2]dioxaborolan-2-yl)phenyl]thiophene-2-carbonitrileHCID 45790121Methyl 3-bromoimidazo[1,2-A]pyridine-7-carboxylate

Product 2

HCID 222AmmoniaHCID 99469203-[3-(2-Cyanothien-3-yl)phenyl]imidazo[1,2-alpha]pyridine-7-carboxylic acid methyl esterYield 132.9%

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 80711,2-DimethoxyethaneSolvent

Conditions

Temperature
80 °C

Procedure

3-Bromoimidazo[1,2-α]pyridine-7-carboxylic acid methyl ester (0.63 g, 2.47 mmol) and 3-[3-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)phenyl]thiophene-2-carbonitrile (0.55 g, 1.76 mmol) were suspended in 1,2-dimethoxyethane (10 ml) and 2N sodium carbonate solution (5 ml) and degassed with nitrogen for 30 min before addition of tetrakis(triphenylphosphine)palladium(0) (0.14 g, 0.12 mmol). The mixture was heated at 80° C. for 18 h then cooled to room temperature. The mixture was partitioned between ethyl acetate (100 ml) and water (50 ml). The organic layer was washed with brine, dried over sodium sulfate and pre-adsorbed onto silica gel. Purification by silica gel chromatography eluting with dichloromethane/methanol/conc. ammonia (gradient 99:1:0.1 through to 97:2:0.2) gave the title compound (0.59 g, 94%) as pale brown needles. 1H NMR (400 MHz, CDCl3) δH 3.98 (3H, s), 7.35 (1H, d, J 5), 7.48 (1H, dd, J 7 and 2), 7.65-7.75 (3H, m), 7.93 (2H, m), 8.43 (1H, s), 8.54 (1H, dd, J 7 and 1); m/z (ES+) 360 (M++H).

Workup

  1. temperaturethen cooled to room temperature
  2. customThe mixture was partitioned between ethyl acetate (100 ml) and water (50 ml)
  3. washThe organic layer was washed with brine
  4. dry with materialdried over sodium sulfate and pre-adsorbed onto silica gel
  5. customPurification by silica gel chromatography
  6. washeluting with dichloromethane/methanol/conc

Sources & evidence

ORD record
ord-53c3a5e244e542cb83555ce1314396f7
Source dataset
uspto-grants-2005_03
Patent number
US06872731B2

Reaction notes

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