1,3-Dimethyl-2-imidazolidinone → N-[4-(4-Fluoro-2-methoxy-phenyl)-6-methyl-pyridazin-3-yl]-3-methanesulfonyl-N-methyl-5-trifluoromethyl-benzamide

HRID 403374Notes

Reaction equation

HRID 403374 reaction equation
Cl[C:2]1[N:7]=[N:6][C:5]([N:8]([CH3:25])[C:9](=[O:24])[C:10]2[CH:15]=[C:14]([C:16]([F:19])([F:18])[F:17])[CH:13]=[C:12]([S:20]([CH3:23])(=[O:22])=[O:21])[CH:11]=2)=[C:4]([C:26]2[CH:31]=[CH:30][C:29]([F:32])=[CH:28][C:27]=2[O:33][CH3:34])[CH:3]=1.[Cl-].C[Zn+].[CH3:38]N1CCN(C)C1=O.C(=O)(O)[O-].[Na+]>O1CCCC1.C(OCC)(=O)C>[F:32][C:29]1[CH:30]=[CH:31][C:26]([C:4]2[CH:3]=[C:2]([CH3:38])[N:7]=[N:6][C:5]=2[N:8]([CH3:25])[C:9](=[O:24])[C:10]2[CH:15]=[C:14]([C:16]([F:18])([F:17])[F:19])[CH:13]=[C:12]([S:20]([CH3:23])(=[O:21])=[O:22])[CH:11]=2)=[C:27]([O:33][CH3:34])[CH:28]=1

Participants

7

Reactant 4

HCID 66611,3-Dimethyl-2-imidazolidinoneHCID 516892Sodium BicarbonateHCID 71766083HCID 71766083, compoundHCID 178477797HCID 178477797, compound

Product 1

HCID 71766084N-[4-(4-Fluoro-2-methoxy-phenyl)-6-methyl-pyridazin-3-yl]-3-methanesulfonyl-N-methyl-5-trifluoromethyl-benzamide

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
60 °C

Procedure

To a solution of N-[6-chloro-4-(4-fluoro-2-methoxy-phenyl)-pyridazin-3-yl]-3-methanesulfonyl-N-methyl-5-trifluoromethyl-benzamide (100 mg, 193 mmol, example 1) in tetrahydrofuran (2 mL) was added methylzinc chloride (2M solution in tetrahydrofuran, 145 μL, 290 mmol) and 1,3-dimethyl-2-imidazolidinone (400 μL, CAS RN 80-73-9) and PEPPSI-IPr (2.62 mg, 3.86 μmol, CAS RN 905459-27-0). The reaction mixture was stirred at 60° C. for 5 hours, poured on 10% aqueous sodium bicarbonate solution (30 mL) and ethyl acetate (30 mL) and the layers were separated. The aqueous layer was extracted a second time with ethyl acetate (30 mL). The organic layers were washed with brine (30 mL), dried over magnesium sulfate, filtered and concentrated under vacuum. The compound was purified by silica gel chromatography on a 20 g column using an MPLC (Flashmaster) system eluting with a gradient of n-heptane:ethyl acetate (100:0 to 0:100). Light brown solid (70 mg, 72.9%). MS (ESI+): m/z=498.110 ([M+H]+).

Workup

  1. customthe layers were separated
  2. extractionThe aqueous layer was extracted a second time with ethyl acetate (30 mL)
  3. washThe organic layers were washed with brine (30 mL)
  4. dry with materialdried over magnesium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated under vacuum
  7. customThe compound was purified by silica gel chromatography on a 20 g column
  8. washeluting with a gradient of n-heptane:ethyl acetate (100:0 to 0:100)

Sources & evidence

ORD record
ord-5da0f6f10d2f47c9acf258a59ff8efdd
Source dataset
uspto-grants-2014_06
Patent number
US08748434B2

Reaction notes

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