1-Naphthol → 4-methyl-2-[4-(naphthalen-1-yloxy)-6-oxo-6H-pyridazin-1-yl]-pentanoic acid [1-((R)-2,2-dimethyl-[1,3]dioxolan-4-ylmethyl)-1H-pyrazol-3-yl]-amide

HRID 2381531Notes

Reaction equation

HRID 2381531 reaction equation
[CH3:1][C:2]1([CH3:38])[O:6][C@H:5]([CH2:7][N:8]2[CH:12]=[CH:11][C:10]([NH:13][C:14](=[O:37])[CH:15]([N:20]3[C:25](=[O:26])[CH:24]=[C:23]([O:27]N4C5C=CC=CC=5N=N4)[CH:22]=[N:21]3)[CH2:16][CH:17]([CH3:19])[CH3:18])=[N:9]2)[CH2:4][O:3]1.C(=O)([O-])[O-].[Cs+].[Cs+].[C:45]1(O)[C:54]2[C:49](=[CH:50][CH:51]=[CH:52][CH:53]=2)[CH:48]=[CH:47][CH:46]=1>C(#N)C>[CH3:1][C:2]1([CH3:38])[O:6][C@H:5]([CH2:7][N:8]2[CH:12]=[CH:11][C:10]([NH:13][C:14](=[O:37])[CH:15]([N:20]3[C:25](=[O:26])[CH:24]=[C:23]([O:27][C:53]4[C:54]5[C:49](=[CH:48][CH:47]=[CH:46][CH:45]=5)[CH:50]=[CH:51][CH:52]=4)[CH:22]=[N:21]3)[CH2:16][CH:17]([CH3:18])[CH3:19])=[N:9]2)[CH2:4][O:3]1

Participants

5

Reactant 3

HCID 70051-NaphtholHCID 10796Cesium carbonateHCID 669004582-[4-(benzotriazol-1-yloxy)-6-oxo-6H-pyridazin-1-yl]-4-methyl-pentanoic acid [1-((R)-2,2-dimethyl-[1,3]dioxolan-4-ylmethyl)-1H-pyrazol-3-yl]-amide

Product 1

HCID 668929594-methyl-2-[4-(naphthalen-1-yloxy)-6-oxo-6H-pyridazin-1-yl]-pentanoic acid [1-((R)-2,2-dimethyl-[1,3]dioxolan-4-ylmethyl)-1H-pyrazol-3-yl]-amideYield 68.9%

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]-4-methyl-pentanoic acid [1-((R)-2,2-dimethyl-[1,3]dioxolan-4-ylmethyl)-1H-pyrazol-3-yl]-amide (0.30 g, 0.57 mmol) in acetonitrile (12 mL, 0.048M) was treated with cesium carbonate (0.37 g, 1.14 mmol) and naphthalen-1-ol (0.10 g, 0.69 mmol). The resulting reaction mixture was stirred at 25° C. for 2 h. The reaction mixture was then concentrated in vacuo and partitioned between water (100 mL) and ethyl acetate (100 mL). The organics were washed with a saturated aqueous sodium chloride solution (50 mL), dried over magnesium sulfate, filtered, rinsed, and concentrated in vacuo. Silica gel column chromatography (AnaLogix 40 g, 25-75% ethyl acetate/hexanes) afforded 4-methyl-2-[4-(naphthalen-1-yloxy)-6-oxo-6H-pyridazin-1-yl]-pentanoic acid [1-((R)-2,2-dimethyl-[1,3]dioxolan-4-ylmethyl)-1H-pyrazol-3-yl]-amide (208.7 mg, 68%) as a light orange solid as a mixture of diastereomers.

Workup

  1. customThe resulting reaction mixture
  2. concentrationThe reaction mixture was then concentrated in vacuo
  3. custompartitioned between water (100 mL) and ethyl acetate (100 mL)
  4. washThe organics were washed with a saturated aqueous sodium chloride solution (50 mL)
  5. dry with materialdried over magnesium sulfate
  6. filtrationfiltered
  7. washrinsed
  8. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-ba4c88b4e973468b91d41c5815babeb6
Source dataset
uspto-grants-2012_09
Patent number
US08258134B2

Reaction notes

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