Ethyl Acetate → 2-Bromo-5-cyano-4-(cyclopropanecarbonylamino)-6-methylbiphenyl-3-yl cyclopropanecarboxylate

반응식

[NH2:1][C:2]1[C:7]([OH:8])=[C:6]([Br:9])[C:5]([C:10]2[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=2)=[C:4]([CH3:16])[C:3]=1[C:17]#[N:18].C(N([CH:25]([CH3:27])[CH3:26])CC)(C)C.[CH:28]1([C:31](Cl)=[O:32])[CH2:30][CH2:29]1.[C:34](OCC)(=[O:36])C>>[CH:28]1([C:31]([O:8][C:7]2[C:6]([Br:9])=[C:5]([C:10]3[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=3)[C:4]([CH3:16])=[C:3]([C:17]#[N:18])[C:2]=2[NH:1][C:34]([CH:25]2[CH2:27][CH2:26]2)=[O:36])=[O:32])[CH2:30][CH2:29]1

참가 물질

반응물 4

HCID 8857Ethyl Acetate2회

HCID 77637Cyclopropanecarbonyl chloride

HCID 81531Diisopropylethylamine

HCID 860974494-Amino-6-bromo-5-hydroxy-2-methylbiphenyl-3-carbonitrile

생성물 1

HCID 866308142-Bromo-5-cyano-4-(cyclopropanecarbonylamino)-6-methylbiphenyl-3-yl cyclopropanecarboxylate

실험 절차

Under nitrogen atmosphere, 4-amino-6-bromo-5-hydroxy-2-methylbiphenyl-3-carbonitrile (I-42) (150 mg, 0.495 mmol) was dissolved in ethyl acetate (6 ml), diisopropylethylamine (431 μl, 2.48 mmol) was added, followed by cooling in an ice-water bath. Cyclopropanecarbonyl chloride (112 μl, 1.24 mmol) was dropwise added to it, followed by stirring overnight with restoring to room temperature. The reaction liquid was diluted with ethyl acetate, washed with saturated brine, then dried over anhydrous magnesium sulfate, concentrated under reduced pressure. The residue was purified by silica gel column chromatography (n-hexane:ethyl acetate=5:1) to obtain 2-bromo-5-cyano-4-(cyclopropanecarbonylamino)-6-methylbiphenyl-3-yl cyclopropanecarboxylate (87 mg) and a mixture of (2-bromo-5-cyano-3-hydroxy-6-methylbiphenyl-4-yl)cyclopropanecarboxamide and 4-amino-2-bromo-5-cyano-6-methylbiphenyl-4-yl cyclopropanecarboxylate (110 mg). Subsequently, 2-bromo-5-cyano-4-(cyclopropanecarbonylamino)-6-methylbiphenyl-3-yl cyclopropanecarboxylate was dissolved in ethanol (30 ml), aqueous 0.1 N sodium hydroxide solution (5.94 ml) was added, followed by stirring overnight at room temperature. Ethanol was evaporated away under reduced pressure, then the residue was dissolved in ethyl acetate, followed by successively washing with 1 N hydrochloric acid, saturated brine, dried on anhydrous magnesium sulfate, concentrated under reduced pressure to obtain (2-bromo-5-cyano-3-hydroxy-6-methylbiphenyl-4-yl)cyclopropanecarboxamide (56 mg) as a colorless oil.