Sodium Hydroxide → 6-[(E)-N-hydroxy-C-[(2R)-2-(2-methylphenyl)-2-(4-methylsulfonylphenyl)ethyl]carbonimidoyl]-2-methylpyridazin-3-one

HRID 1527980Notes

Reaction equation

HRID 1527980 reaction equation
[NH:1]1CCC[C@H]1C(O)=O.[OH-:9].[Na+].Br[C:12]1[CH:17]=[CH:16][C:15]([C@H:18]([C:33]2[CH:38]=[CH:37][CH:36]=[CH:35][C:34]=2[CH3:39])[CH2:19][C:20]2([C:25]3[CH:26]=[CH:27][C:28](=[O:32])[N:29]([CH3:31])[N:30]=3)OCCO2)=[CH:14][CH:13]=1.[CH3:40][S:41]([O-:43])=[O:42].[Na+]>[Cu]I.CS(C)=O>[OH:9]/[N:1]=[C:20](/[C:25]1[CH:26]=[CH:27][C:28](=[O:32])[N:29]([CH3:31])[N:30]=1)\[CH2:19][C@H:18]([C:15]1[CH:16]=[CH:17][C:12]([S:41]([CH3:40])(=[O:43])=[O:42])=[CH:13][CH:14]=1)[C:33]1[CH:38]=[CH:37][CH:36]=[CH:35][C:34]=1[CH3:39]

Participants

7

Reactant 4

HCID 14798Sodium HydroxideHCID 145742L-ProlineHCID 2733271Sodium methanesulfinateHCID 86684810(R)-6-(2-(2-(4-Bromophenyl)-2-o-tolylethyl)-1,3-dioxolan-2-yl)-2-methylpyridazin-3(2H)-one

Product 1

HCID 1366450646-[(E)-N-hydroxy-C-[(2R)-2-(2-methylphenyl)-2-(4-methylsulfonylphenyl)ethyl]carbonimidoyl]-2-methylpyridazin-3-oneYield 36.2%

Reagents, catalysts & solvents 2

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 679Dimethyl SulfoxideSolvent

Procedure

L-proline (7.5 mg, 65 μmol) was combined with dimethyl sulfoxide (1 ml), then sodium hydroxide (2.6 mg, 65 μmol) was added and the reaction stirred at room temperature for 30 min, then (R)-6-(2-(2-(4-bromophenyl)-2-o-tolylethyl)-1,3-dioxolan-2-yl)-2-methylpyridazin-3(2H)-one (37 mg, 81 μmol), sodium methanesulfinate (68 mg, 650 μmol) and copper(I) iodide (12.4 mg, 65 μmol) were added. The reaction mixture was heated at 120° C. for 22 h, then partitioned between water and ethyl acetate. The organic layer was washed with brine, dried over magnesium sulfate, filtered, and evaporated. Chromatography (SiO2; gradient heptane-ethyl acetate) produced the title compound (10 mg, 27%). White semisolid, MS: 455.2 [M+H]+.

Workup

  1. temperatureThe reaction mixture was heated at 120° C. for 22 h
  2. custompartitioned between water and ethyl acetate
  3. washThe organic layer was washed with brine
  4. dry with materialdried over magnesium sulfate
  5. filtrationfiltered
  6. customevaporated

Sources & evidence

ORD record
ord-8a1c10869cf34673b332e4db3a4704e1
Source dataset
uspto-grants-2015_07
Patent number
US09090565B2

Reaction notes

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