Potassium Carbonate → 3-cyclopentyl-2-[4-(1H-indol-4-yloxy)-6-oxo-6H-pyridazin-1-yl]-propionic acid methyl ester

HRID 2381379Notes

Reaction equation

HRID 2381379 reaction equation
[NH:1]1[C:9]2[CH:8]=[CH:7][CH:6]=[C:5]([OH:10])[C:4]=2[CH:3]=[CH:2]1.C(=O)([O-])[O-].[K+].[K+].[CH3:17][O:18][C:19](=[O:35])[CH:20]([N:27]1[C:32](=[O:33])[CH:31]=[C:30](I)[CH:29]=[N:28]1)[CH2:21][CH:22]1[CH2:26][CH2:25][CH2:24][CH2:23]1>CN(C)C=O>[CH3:17][O:18][C:19](=[O:35])[CH:20]([N:27]1[C:32](=[O:33])[CH:31]=[C:30]([O:10][C:5]2[CH:6]=[CH:7][CH:8]=[C:9]3[C:4]=2[CH:3]=[CH:2][NH:1]3)[CH:29]=[N:28]1)[CH2:21][CH:22]1[CH2:23][CH2:24][CH2:25][CH2:26]1

Participants

5

Reactant 3

HCID 11430Potassium CarbonateHCID 754211H-indol-4-olHCID 668748863-cyclopentyl-2-(4-iodo-6-oxo-6H-pyridazin-1-yl)-propionic acid methyl ester2×

Product 1

HCID 668911313-cyclopentyl-2-[4-(1H-indol-4-yloxy)-6-oxo-6H-pyridazin-1-yl]-propionic acid methyl ester

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
120 °C

Procedure

A solution of 1H-indol-4-ol (3.5 g, 26.6 mmol) in N,N-dimethylformamide (40 mL) was treated with potassium carbonate (5.4 g, 39 mmol) and 3-cyclopentyl-2-(4-iodo-6-oxo-6H-pyridazin-1-yl)-propionic acid methyl ester (Intermediate 73 step 2.10 g, 26.6 mmol). The resulting reaction mixture was heated to 120° C. for 2 h. At this time, the reaction was cooled to 25° C. and then concentrated in vacuo. The residue was partitioned between water and methylene chloride. The aqueous phase was back extracted with methylene chloride. The combined organics was washed with a saturated aqueous sodium chloride solution, dried over anhydrous sodium sulfate, filtered and concentrated in vacuo. Chromatography afforded 3-cyclopentyl-2-[4-(1H-indol-4-yloxy)-6-oxo-6H-pyridazin-1-yl]-propionic acid methyl ester as a light oil (6.1 g, 60%).

Workup

  1. customThe resulting reaction mixture
  2. temperatureAt this time, the reaction was cooled to 25° C.
  3. concentrationconcentrated in vacuo
  4. customThe residue was partitioned between water and methylene chloride
  5. extractionThe aqueous phase was back extracted with methylene chloride
  6. washThe combined organics was washed with a saturated aqueous sodium chloride solution
  7. dry with materialdried over anhydrous sodium sulfate
  8. filtrationfiltered
  9. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-e2eef24ca91b40c48c169cea41b1f0ce
Source dataset
uspto-grants-2012_09
Patent number
US08258134B2

Reaction notes

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