Iodine → HCID 68743737, compound

HRID 238655Notes

Reaction equation

HRID 238655 reaction equation
[CH:1]([C:3]1[N:4]=[C:5]([CH:8]2[CH2:13][CH2:12][N:11]([C:14](=[O:26])[CH2:15][N:16]3[C:20]([CH3:21])=[CH:19][C:18]([C:22]([F:25])([F:24])[F:23])=[N:17]3)[CH2:10][CH2:9]2)[S:6][CH:7]=1)=O.[CH3:27][NH:28][CH:29]([C:32]1[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=1)[CH2:30][NH2:31].C(=O)([O-])[O-].[K+].[K+].II>C(O)(C)(C)C>[CH3:27][N:28]1[CH:29]([C:32]2[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=2)[CH2:30][N:31]=[C:1]1[C:3]1[N:4]=[C:5]([CH:8]2[CH2:13][CH2:12][N:11]([C:14](=[O:26])[CH2:15][N:16]3[C:20]([CH3:21])=[CH:19][C:18]([C:22]([F:25])([F:24])[F:23])=[N:17]3)[CH2:10][CH2:9]2)[S:6][CH:7]=1

Participants

6

Reactant 4

HCID 807IodineHCID 11430Potassium CarbonateHCID 98060N1-Methyl-1-phenylethylenediamineHCID 86631244HCID 86631244, compound2×

Product 1

HCID 68743737HCID 68743737, compound

Reagents, catalysts & solvents 1

HCID 6386tert-ButanolSolvent

Procedure

To a solution of 4-(4-formyl-2-thiazolyl)-1-[[5-methyl-3-(trifluoromethyl)-1H-pyrazol-1-yl]acetyl]piperidine (i.e. the product of Example 2, Step B) (0.8 g, 2.07 mmol) in tert-butanol (5 mL) was added N1-methyl-1-phenyl-1,2-ethanediamine (43.57 mg, 0.29 mmol). The reaction mixture was stirred at room temperature under a nitrogen atmosphere for 30 minutes, and then potassium carbonate (107.8 mg, 0.78 mmol) and iodine (43.57 mg, 0.33 mmol) were added. The reaction mixture was stirred at 70° C. for 3 h and then quenched by addition of saturated aqueous sodium sulfite solution until the iodine color almost disappeared. The reaction mixture was extracted with chloroform, and the organic layer was washed with saturated aqueous sodium bicarbonate solution and brine, dried (Na2SO4), filtered and concentrated. The residue was purified by preparative thin-layer chromatography on silica gel using a mixture of 94% ethyl acetate, 5% methanol and 1% triethylamine as eluant to give 64 mg of the title product, a compound of the present invention, as an oil.

Workup

  1. stirringThe reaction mixture was stirred at 70° C. for 3 h
  2. customquenched by addition of saturated aqueous sodium sulfite solution until the iodine color
  3. extractionThe reaction mixture was extracted with chloroform
  4. washthe organic layer was washed with saturated aqueous sodium bicarbonate solution and brine
  5. dry with materialdried (Na2SO4)
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customThe residue was purified by preparative thin-layer chromatography on silica gel using
  9. additiona mixture of 94% ethyl acetate, 5% methanol and 1% triethylamine as eluant

Sources & evidence

ORD record
ord-706266a5727f420c9b9fe0c6ee940cc8
Source dataset
uspto-grants-2014_02
Patent number
US08642634B2

Reaction notes

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