Potassium Carbonate → Methyl 4-oxo-4-[[5-(2-thienyl)-2-pyridyl]amino]butanoate

HRID 526001Notes

Reaction equation

HRID 526001 reaction equation
Br[C:2]1[CH:3]=[CH:4][C:5]([NH:8][C:9](=[O:16])[CH2:10][CH2:11][C:12]([O:14][CH3:15])=[O:13])=[N:6][CH:7]=1.BrC1C=CC(N)=NC=1.[S:25]1[CH:29]=[CH:28][CH:27]=[C:26]1B(O)O.C(=O)([O-])[O-].[K+].[K+]>COCCOC.O.CC(C)([P](C(C)(C)C)([Pd][P](C(C)(C)C)(C(C)(C)C)C(C)(C)C)C(C)(C)C)C>[O:16]=[C:9]([NH:8][C:5]1[CH:4]=[CH:3][C:2]([C:26]2[S:25][CH:29]=[CH:28][CH:27]=2)=[CH:7][N:6]=1)[CH2:10][CH2:11][C:12]([O:14][CH3:15])=[O:13]

Participants

8

Reactant 4

HCID 11430Potassium CarbonateHCID 706222-Amino-5-bromopyridineHCID 1506825Methyl 4-[(5-bromopyridin-2-yl)amino]-4-oxobutanoateHCID 27339602-Thiopheneboronic acid

Product 1

HCID 89444364Methyl 4-oxo-4-[[5-(2-thienyl)-2-pyridyl]amino]butanoate

Reagents, catalysts & solvents 3

HCID 178418851HCID 178418851, compoundCatalystHCID 962WaterSolventHCID 80711,2-DimethoxyethaneSolvent

Conditions

Temperature
130 °C

Procedure

In a microwave tube was charged with methyl 4-[(5-bromo-2-pyridyl)amino]-4-oxo-butanoate (commercially available or prepared as described in example II using as starting material the commercially available: 5-bromo-2-aminopyridine; 200 mg, 0.696 mmol, 1 equiv.), 2-thienylboronic acid (3 equiv., 2.09 mmol, 3 equiv.), bis(tri-tert-butylphosphine)palladium(0) (22 mg, 0.043 mmol, 0.06 equiv.), potassium carbonate (179 mg, 1.28 mmol, 1.8 equiv.) and dissolved in glycol dimethyl ether (5 ml)/water (2 ml). The reaction mixture was heated at 130° C. for 20 minutes in the microwave. The reaction was stopped and the solution was partitioned between ethyl acetate and alkaline water. The aqueous layer was separated and extracted with ethyl acetate (2×). The combined organic layer was dried on magnesium sulfate, and then concentrated under vacuum. The solid obtained was purified by flash chromatography (RF-machine) eluting with a gradient of cyclohexane-ethyl acetate to give methyl 4-oxo-4-[[5-(2-thienyl)-2-pyridyl]amino]butanoate A71 (8%). %). LC-MS (Method F) RT 0.85, 291 (M+H+). The aqueous layer was acidified with hydrogen chloride until pH 1-2 and extracted with ethyl acetate (2×). The combined organic layer was dried on magnesium sulfate, and then concentrated under vacuum. The solid was washed with ethyl acetate, filtered and dried to give 4-oxo-4-[[5-(2-thienyl)-2-pyridyl]amino]butanoic acid A72 (31% yield). %). LC-MS (Method F) RT 0.74, 277 (M+H+).

Workup

  1. customprepared
  2. customthe solution was partitioned between ethyl acetate
  3. customThe aqueous layer was separated
  4. extractionextracted with ethyl acetate (2×)
  5. customThe combined organic layer was dried on magnesium sulfate
  6. concentrationconcentrated under vacuum
  7. customThe solid obtained
  8. customwas purified by flash chromatography (RF-machine)
  9. washeluting with a gradient of cyclohexane-ethyl acetate

Sources & evidence

ORD record
ord-4ec90490c71546499ac84fa2ac619eef
Source dataset
uspto-grants-2016_05
Patent number
US09345244B2

Reaction notes

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