HCID 66933595, compound → HCID 59541743, compound

HRID 1928644Notes

Reaction equation

HRID 1928644 reaction equation
COCN[C:5]([C:7]1[CH:8]=[N:9][N:10]([C:12]2[CH:17]=[CH:16][C:15]([O:18][CH2:19][CH2:20][CH2:21][N:22]3[CH2:26][CH2:25][CH2:24][C@H:23]3[CH3:27])=[CH:14][CH:13]=2)[CH:11]=1)=[O:6].[F:28][C:29]1[CH:34]=[CH:33][C:32]([Mg]Br)=[CH:31][CH:30]=1>O1CCCC1.[Cl-].[NH4+]>[F:28][C:29]1[CH:34]=[CH:33][C:32]([C:5]([C:7]2[CH:8]=[N:9][N:10]([C:12]3[CH:13]=[CH:14][C:15]([O:18][CH2:19][CH2:20][CH2:21][N:22]4[CH2:26][CH2:25][CH2:24][C@H:23]4[CH3:27])=[CH:16][CH:17]=3)[CH:11]=2)=[O:6])=[CH:31][CH:30]=1

Participants

5

Reactant 2

HCID 66933595HCID 66933595, compoundHCID 178418676HCID 178418676, compound

Product 1

HCID 59541743HCID 59541743, compound

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolvent2×HCID 25517Ammonium ChlorideSolvent

Procedure

To a solution of 1-(4-{3-[(2R)-2-methylpyrrolidin-1-yl]propoxy}phenyl)-1H-pyrazole-4-carboxylic acid methoxymethylamide obtained in Example 23-(1) (0.25 g) in tetrahydrofuran (3 mL), a solution of 4-fluorophenylmagnesium bromide in tetrahydrofuran (1.0 M, 4.0 mL) was added dropwise in an ice bath and stirred at room temperature for 2 hours. The reaction mixture was diluted with saturated aqueous ammonium chloride and extracted with chloroform. The organic layer was dried over sodium sulfate and concentrated under reduced pressure, and the resulting residue was purified by NH-type silica gel column chromatography (eluting solvent: hexane:ethyl acetate=5:1 to 4:1) and silica gel column chromatography (eluting solvent: chloroform:methanol=95:5) to give the titled compound (0.11 g) as a light-blue solid.

Workup

  1. extractionextracted with chloroform
  2. dry with materialThe organic layer was dried over sodium sulfate
  3. concentrationconcentrated under reduced pressure
  4. customthe resulting residue was purified by NH-type silica gel column chromatography (eluting solvent: hexane:ethyl acetate=5:1 to 4:1) and silica gel column chromatography (eluting solvent: chloroform:methanol=95:5)

Sources & evidence

ORD record
ord-f73468e00c8e418284ae586ede599649
Source dataset
uspto-grants-2012_05
Patent number
US08183387B2

Reaction notes

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