Potassium Carbonate → HCID 66900498, compound

HRID 2381536Notes

Reaction equation

HRID 2381536 reaction equation
[CH3:1][N:2]1[CH:6]=[CH:5][C:4]([NH:7][C:8](=[O:31])[CH:9]([N:14]2[C:19](=[O:20])[CH:18]=[C:17]([O:21][C:22]3[CH:30]=[CH:29][CH:28]=[C:27]4[C:23]=3[CH:24]=[CH:25][NH:26]4)[CH:16]=[N:15]2)[CH2:10][CH:11]([CH3:13])[CH3:12])=[N:3]1.[C:32](=O)([O-])[O-].[K+].[K+].[CH3:38][C:39]1([CH3:55])[O:43][C@@H:42](OS(C2C=CC(C)=CC=2)(=O)=O)[CH2:41][O:40]1>CN(C)C=O>[CH3:1][N:2]1[CH:6]=[CH:5][C:4]([NH:7][C:8](=[O:31])[CH:9]([N:14]2[C:19](=[O:20])[CH:18]=[C:17]([O:21][C:22]3[CH:30]=[CH:29][CH:28]=[C:27]4[C:23]=3[CH:24]=[CH:25][N:26]4[CH2:32][C@@H:42]3[CH2:41][O:40][C:39]([CH3:55])([CH3:38])[O:43]3)[CH:16]=[N:15]2)[CH2:10][CH:11]([CH3:13])[CH3:12])=[N:3]1

Participants

5

Reactant 3

HCID 11430Potassium CarbonateHCID 66893591HCID 66893591, compoundHCID 86635181HCID 86635181, compound

Product 1

HCID 66900498HCID 66900498, compoundYield 21%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
90 °C

Procedure

A solution of 2-[4-(1H-indol-4-yloxy)-6-oxo-6H-pyridazin-1-yl]-4-methyl-pentanoic acid (1-methyl-1H-pyrazol-3-yl)-amide (34.0 mg, 0.0809 mmol) in N,N-dimethylformamide (1.0 mL) was treated with potassium carbonate (23.1 mg, 0.16 mmol) and toluene-4-sulfonic acid (S)-2,2-dimethyl-[1,3]dioxolan-4-yl ester (25.5 mg, 0.08 mmol). The resulting reaction mixture was heated at 90° C. overnight. At this time, the reaction mixture was allowed to cool to 25° C., concentrated in vacuo and was treated with a saturated aqueous ammonium chloride solution (2 drops). The reaction was then concentrated in vacuo onto silica gel. Silica gel column chromatography (AnaLogix 12 g, 1-5% methanol/methylene chloride) afforded 2-{4-[1-((R)-2,2-dimethyl-[1,3]dioxolan-4-ylmethyl)-1H-indol-4-yloxy]-6-oxo-6H-pyridazin-1-yl}-4-methyl-pentanoic acid (1-methyl-1H-pyrazol-3-yl)-amide (9.0 mg, 21%) as a viscous brown oil.

Workup

  1. customThe resulting reaction mixture
  2. temperatureto cool to 25° C.
  3. concentrationconcentrated in vacuo
  4. additionwas treated with a saturated aqueous ammonium chloride solution (2 drops)
  5. concentrationThe reaction was then concentrated in vacuo onto silica gel

Sources & evidence

ORD record
ord-b6d9a4e90f254e2aa09fe6754886363c
Source dataset
uspto-grants-2012_09
Patent number
US08258134B2

Reaction notes

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