Methyl iodide → 4-(3,4-Dichloro-phenyl)-2-methyl-5-pyridin-4-yl-1-pyridin-3-ylmethyl-1,2-dihydro-pyrazol-3-one

HRID 1064088Notes

Reaction equation

HRID 1064088 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([CH:9]2[CH:13]([C:14]3[CH:19]=[CH:18][N:17]=[CH:16][CH:15]=3)[N:12]([CH2:20][C:21]3[CH:22]=[N:23][CH:24]=[CH:25][CH:26]=3)[NH:11][C:10]2=[O:27])[CH:5]=[CH:6][C:7]=1[Cl:8].[Li+].[CH3:29][Si]([N-][Si](C)(C)C)(C)C.IC>C1COCC1>[Cl:1][C:2]1[CH:3]=[C:4]([C:9]2[C:10](=[O:27])[N:11]([CH3:29])[N:12]([CH2:20][C:21]3[CH:22]=[N:23][CH:24]=[CH:25][CH:26]=3)[C:13]=2[C:14]2[CH:15]=[CH:16][N:17]=[CH:18][CH:19]=2)[CH:5]=[CH:6][C:7]=1[Cl:8]

Participants

5

Reactant 3

HCID 6328Methyl iodideHCID 2733832Lithium HexamethyldisilazideHCID 222779924-(3,4-Dichloro-phenyl)-5-pyridin-4-yl-1-pyridin-3-ylmethyl-pyrazolidin-3-one

Product 1

HCID 104317304-(3,4-Dichloro-phenyl)-2-methyl-5-pyridin-4-yl-1-pyridin-3-ylmethyl-1,2-dihydro-pyrazol-3-one

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
0 °C

Procedure

In a 100 mL round bottom flask, was added 70 mg 4-(3,4-Dichloro-phenyl)-5-pyridin-4-yl-1-pyridin-3-ylmethyl-pyrazolidin-3-one and 10 mL THF, stirred at 0° C. under nitrogen. 0.26 mL 1 M LHMDS in THF was added drop wise. After stirred at 0° C. for 30 min. 0.017 mL iodomethane was added drop wise. The resulted mixture was stirred from 0° C. to rt for 2 hour, quenched with 20 mL sat. NH4Cl, extracted with dichloromethane 3×25 mL. The crude MS showed the desired 4-(3,4-Dichloro-phenyl)-2-methyl-5-pyridin-4-yl-1-pyridin-3-ylmethyl-pyrazolidin-3-one was there, MS (ES+): 413 (M+H)+. The organic phase was dried over anhydrous Na2SO4. After purification by flash chromatography, the 4-(3,4-Dichloro-phenyl)-5-pyridin-4-yl-1-pyridin-3-ylmethyl-pyrazolidin-3-one was oxidized on column and obtained the 4-(3,4-Dichloro-phenyl)-2-methyl-5-pyridin-4-yl-1-pyridin-3-ylmethyl-1,2-dihydro-pyrazol-3-one 12 mg as light yellow solid. MS (ES+): 411 (M+H)+.

Workup

  1. stirringAfter stirred at 0° C. for 30 min
  2. stirringThe resulted mixture was stirred from 0° C. to rt for 2 hour
  3. customquenched with 20 mL sat. NH4Cl
  4. extractionextracted with dichloromethane 3×25 mL
  5. dry with materialThe organic phase was dried over anhydrous Na2SO4
  6. customAfter purification by flash chromatography

Sources & evidence

ORD record
ord-bb1610e48e98447ea0c815de2a4e5399
Source dataset
uspto-grants-2005_11
Patent number
US06967254B2

Reaction notes

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