Cesium carbonate → 2-{4-[2-(2-chloro-phenyl)-ethoxy]-6-oxo-6H-pyridazin-1-yl}-3-cyclopentyl-N-[1-((R)-2,2-dimethyl-[1,3]dioxolan-4-ylmethyl)-1H-pyrazol-3-yl]-propionamide

HRID 2381538Notes

Reaction equation

HRID 2381538 reaction equation
N1([O:10][C:11]2[CH:12]=[N:13][N:14]([CH:18]([CH2:35][CH:36]3[CH2:40][CH2:39][CH2:38][CH2:37]3)[C:19]([NH:21][C:22]3[CH:26]=[CH:25][N:24]([CH2:27][C@@H:28]4[CH2:32][O:31][C:30]([CH3:34])([CH3:33])[O:29]4)[N:23]=3)=[O:20])[C:15](=[O:17])[CH:16]=2)C2C=CC=CC=2N=N1.C(=O)([O-])[O-].[Cs+].[Cs+].[Cl:47][C:48]1[CH:53]=[CH:52][CH:51]=[CH:50][C:49]=1[CH2:54][CH2:55]O>C(#N)C>[Cl:47][C:48]1[CH:53]=[CH:52][CH:51]=[CH:50][C:49]=1[CH2:54][CH2:55][O:10][C:11]1[CH:12]=[N:13][N:14]([CH:18]([CH2:35][CH:36]2[CH2:40][CH2:39][CH2:38][CH2:37]2)[C:19]([NH:21][C:22]2[CH:26]=[CH:25][N:24]([CH2:27][C@@H:28]3[CH2:32][O:31][C:30]([CH3:34])([CH3:33])[O:29]3)[N:23]=2)=[O:20])[C:15](=[O:17])[CH:16]=1

Participants

5

Reactant 3

HCID 10796Cesium carbonateHCID 88266o-Chlorophenethylic alcoholHCID 668932872-[4-(benzotriazol-1-yloxy)-6-oxo-6H-pyridazin-1-yl]-3-cyclopentyl-N-[1-((R)-2,2-dimethyl-[1,3]dioxolan-4-ylmethyl)-1H-pyrazol-3-yl]-propionamide

Product 1

HCID 689930362-{4-[2-(2-chloro-phenyl)-ethoxy]-6-oxo-6H-pyridazin-1-yl}-3-cyclopentyl-N-[1-((R)-2,2-dimethyl-[1,3]dioxolan-4-ylmethyl)-1H-pyrazol-3-yl]-propionamideYield 37.1%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Conditions

Temperature
25 °C

Procedure

A solution of 2-[4-(benzotriazol-1-yloxy)-6-oxo-6H-pyridazin-1-yl]-3-cyclopentyl-N-[1-((R)-2,2-dimethyl-[1,3]dioxolan-4-ylmethyl)-1H-pyrazol-3-yl]-propionamide (0.30 g, 0.54 mmol) in acetonitrile (10 mL, 0.055M) was treated with cesium carbonate (0.36 g, 1.10 mmol) and 2-(2-chloro-phenyl)-ethanol (86 μL, 0.65 mmol). The resulting reaction mixture was stirred at 25° C. overnight. The reaction mixture was then heated at 75° C. for 5.5-6 h. At this time, the reaction was partitioned between water and methylene chloride. The organics were dried over sodium sulfate, filtered, rinsed, and concentrated in vacuo. Silica gel column chromatography (AnaLogix 12 g, 50-75% ethyl acetate/hexanes) afforded 2-{4-[2-(2-chloro-phenyl)-ethoxy]-6-oxo-6H-pyridazin-1-yl}-3-cyclopentyl-N-[1-((R)-2,2-dimethyl-[1,3]dioxolan-4-ylmethyl)-1H-pyrazol-3-yl]-propionamide (114.1 mg, 37%) as a light yellow solid as a mixture of diastereomers.

Workup

  1. customThe resulting reaction mixture
  2. temperatureThe reaction mixture was then heated at 75° C. for 5.5-6 h
  3. customAt this time, the reaction was partitioned between water and methylene chloride
  4. dry with materialThe organics were dried over sodium sulfate
  5. filtrationfiltered
  6. washrinsed
  7. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-1a3ebf5b55f9460f8f3e5d5a52efc13f
Source dataset
uspto-grants-2012_09
Patent number
US08258134B2

Reaction notes

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