Hydrochloric Acid → 1-[(R)-4-(6-Benzyl-4,5-dimethyl-pyridazin-3-yl)-2-methyl-3,4,5,6-tetrahydro-2H-[1,2']bipyrazinyl-5'-yl)-2-hydroxy-ethanone

HRID 447120Notes

Reaction equation

HRID 447120 reaction equation
[OH-].[K+].[CH2:3]([C:10]1[N:15]=[N:14][C:13]([N:16]2[CH2:21][CH2:20][N:19]([C:22]3[CH:27]=[N:26][C:25]([C:28](=[O:30])[CH3:29])=[CH:24][N:23]=3)[C@H:18]([CH3:31])[CH2:17]2)=[C:12]([CH3:32])[C:11]=1[CH3:33])[C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][CH:5]=1.C(O)(=[O:36])C.C(O)(=O)C.IC1C=CC=CC=1.Cl.C([O-])(O)=O.[Na+]>CO.O>[CH2:3]([C:10]1[N:15]=[N:14][C:13]([N:16]2[CH2:21][CH2:20][N:19]([C:22]3[CH:27]=[N:26][C:25]([C:28](=[O:30])[CH2:29][OH:36])=[CH:24][N:23]=3)[C@H:18]([CH3:31])[CH2:17]2)=[C:12]([CH3:32])[C:11]=1[CH3:33])[C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][CH:5]=1

Participants

8

Reactant 5

HCID 313Hydrochloric AcidHCID 14797Potassium HydroxideHCID 516892Sodium BicarbonateHCID 12217721Iodo benzene diacetateHCID 451071751-[(R)-4-(6-Benzyl-4,5-dimethyl-pyridazin-3-yl)-2-methyl-3,4,5,6-tetrahydro-2H-[1,2']bipyrazinyl-5'-yl]-ethanone

Product 1

HCID 591915351-[(R)-4-(6-Benzyl-4,5-dimethyl-pyridazin-3-yl)-2-methyl-3,4,5,6-tetrahydro-2H-[1,2']bipyrazinyl-5'-yl)-2-hydroxy-ethanoneYield 58%

Reagents, catalysts & solvents 2

HCID 887MethanolSolvent2×HCID 962WaterSolvent

Procedure

To a solution of KOH (224 mg, 4.0 mmol) and CH3OH (10 mL) is added 1-[(R)-4-(6-benzyl-4,5-dimethyl-pyridazin-3-yl)2-methyl-3,4,5,6-tetrahydro-2H-[1,2′]bipyrazinyl-5′-yl)-ethanone (400 mg, 1.0 mmol) in CH3OH (10 mL) and then iodobenzene diacetate (464 mg, 1.5 mmole) in portions at 0° C. The mixture is stirred at room temperature overnight. The solvent is removed and then extracted with DCM. The organic layer is washed with aqueous NH4Cl and afterwards concentrated to yield crude example 112. This material is dissolved in water and then 6 N HCl (5 mL) is added. The mixture is stirred at room temperature for 3 h. Afterwards it is made basic with NaHCO3 and extracted with DCM. The organic layer is concentrated to give a crude product that is purified by chromatography on silica gel (EtOAc/Heptane: 50%˜100%) to give the title compound (240 mg, 58%) as a yellow solid.

Workup

  1. customat 0° C
  2. customThe solvent is removed
  3. extractionextracted with DCM
  4. washThe organic layer is washed with aqueous NH4Cl
  5. concentrationafterwards concentrated
  6. customto yield crude example 112
  7. stirringThe mixture is stirred at room temperature for 3 h
  8. extractionextracted with DCM
  9. concentrationThe organic layer is concentrated
  10. customto give a crude product that
  11. customis purified by chromatography on silica gel (EtOAc/Heptane: 50%˜100%)

Sources & evidence

ORD record
ord-f9af190d3f1745cc8e6c40c4a223766f
Source dataset
uspto-grants-2013_07
Patent number
US08481542B2

Reaction notes

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