反応式
[NH2:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[CH:13]=[CH:12][C:11]([C:14](=[O:23])[CH2:15][C:16]([CH3:22])([CH3:21])[C:17]([O:19]C)=[O:18])=[CH:10][CH:9]=2)=[CH:4][CH:3]=1.[CH3:24][C:25]1[CH:37]=[CH:36][C:28]2[N:29]=[C:30](S(C)(=O)=O)[O:31][C:27]=2[CH:26]=1.[OH-].[Na+].Cl>ClC(Cl)C.CO>[CH3:21][C:16]([CH3:22])([CH2:15][C:14]([C:11]1[CH:10]=[CH:9][C:8]([C:5]2[CH:4]=[CH:3][C:2]([NH:1][C:30]3[O:31][C:27]4[CH:26]=[C:25]([CH3:24])[CH:37]=[CH:36][C:28]=4[N:29]=3)=[CH:7][CH:6]=2)=[CH:13][CH:12]=1)=[O:23])[C:17]([OH:19])=[O:18]参加物
反応物 4
生成物 1
試薬・触媒・溶媒 2
反応条件
- 温度
- -85 °C
実験手順
To a solution of methyl 4-(4′-amino-1,1′-biphenyl-4-yl)-2,2-dimethyl-4-oxobutanoate (74 mg, 0.24 mmol) in dichloroethane (3 mL), 6-methyl-2-(methylsulfonyl)-1,3-benzoxazole (50 mg, 0.24 mmol) was added, and the mixture was heated at −85° C. overnight. The solvent was removed by rotary evaporation, and the residue was redissolved in DMF (5 mL). A solution of 1 N aqueous NaOH (0.72 mL, 0.72 mmol) was added, and the mixture was heated at 65° C. overnight. A solution of 1 N aqueous HCl (0.24 mL, 0.24 mmol) and methanol (5 mL) were added to the reaction mixture and the crude product was purified by preparative reverse-phase HPLC (water/acetonitrile gradient, containing 0.1% TFA) to afford 2,2-dimethyl-4-{4′-[(6-methyl-1,3-benzoxazol-2-yl)amino]-1,1′-biphenyl-4-yl}-4-oxobutanoic acid as a white solid (32.6 mg, 32.1%). 1H NMR (300 MHz, DMSO-d6) δ 8.00-7.50 (m, 8H), 7.30 (d, 2H), 7.05 (d, 1H), 3.30 (s, 2H), 2.50 (s, 3H), 1.10 (s, 6H); LC-MS ret. time 3.53 min (method 2), m/z 429.17 (MH+).
後処理
- customThe solvent was removed by rotary evaporation
- dissolutionthe residue was redissolved in DMF (5 mL)
- temperaturethe mixture was heated at 65° C. overnight
- customthe crude product was purified by preparative reverse-phase HPLC (water/acetonitrile gradient, containing 0.1% TFA)
出典と根拠
- ORDレコード
- ord-aa6d1bd9da9a4b9d9b4f1e6738a932dd
- 出典データセット
- uspto-grants-2011_09
- 特許番号
- US08013166B2
関連ノート
読み込み中…