Iodine → 4-[4-(4,5-dihydro-1-methyl-5-phenyl-1H-imidazol-2-yl)-2-thiazolyl]-1-[[5-methyl-3-(trifluoromethyl)-1H-pyrazol-1-yl]acetyl]piperidine

HRID 2095991ノート

反応式

HRID 2095991 の反応式
[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.CC1N(CC(N2CCC(C3SC=C(C4C=C(C5C=CC=CC=5)ON=4)N=3)CC2)=O)N=C(C(F)(F)F)C=1.[CH3:62][NH:63][CH:64]([C:67]1[CH:72]=[CH:71][CH:70]=[CH:69][CH:68]=1)[CH2:65][NH2:66].C(=O)([O-])[O-].[K+].[K+].II>C(O)(C)(C)C>[CH3:62][N:63]1[CH:64]([C:67]2[CH:72]=[CH:71][CH:70]=[CH:69][CH:68]=2)[CH2:65][N:66]=[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

参加物

7

反応物 5

HCID 807IodineHCID 11430Potassium CarbonateHCID 98060N1-Methyl-1-phenylethylenediamineHCID 687422261-[[5-methyl-3-(trifluoromethyl)-1H-pyrazol-1-yl]acetyl]-4-[4-(5-phenyl-3-isoxazolyl)-2-thiazolyl]piperidineHCID 866312444-(4-formyl-2-thiazolyl)-1-[[5-methyl-3-(trifluoromethyl)-1H-pyrazol-1-yl]acetyl]piperidine

生成物 1

HCID 687437374-[4-(4,5-dihydro-1-methyl-5-phenyl-1H-imidazol-2-yl)-2-thiazolyl]-1-[[5-methyl-3-(trifluoromethyl)-1H-pyrazol-1-yl]acetyl]piperidine

試薬・触媒・溶媒 1

HCID 6386tert-Butanol溶媒

実験手順

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 as an oil.

後処理

  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

出典と根拠

ORDレコード
ord-fef34ff316314e6abcb093c4f2f4705b
出典データセット
uspto-grants-2013_05
特許番号
US08449898B2

反応ノート

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