反応式
Cl.[F:2][C:3]1[C:4]([F:19])=[CH:5][C:6]2[N:15]=[C:14]([NH2:16])[C:13]3[CH:12]=[C:11]([CH3:17])[S:10][C:9]=3[NH:8][C:7]=2[CH:18]=1.C(N(CC)C(C)C)(C)C.[NH:29]1[CH2:34][CH2:33]N[CH2:31][C@@H:30]1[CH2:35][CH2:36][OH:37]>CS(C)=O.C1(C)C=CC=CC=1.O.C(OCC)(=O)C>[F:2][C:3]1[C:4]([F:19])=[CH:5][C:6]2[N:15]=[C:14]([N:16]3[CH2:33][CH2:34][NH:29][C@@H:30]([CH2:35][CH2:36][OH:37])[CH2:31]3)[C:13]3[CH:12]=[C:11]([CH3:17])[S:10][C:9]=3[NH:8][C:7]=2[CH:18]=1参加物
反応物 3
生成物 1
試薬・触媒・溶媒 3
反応条件
- 温度
- 120 °C
実験手順
Dissolve 6,7-difluoro-2-methyl-4H-3-thia-4,9-diaza-benzo[f]azulen-10-ylamine hydrochloride (1.51, 4.99 mmol), N,N-diisopropylethylamine (0.91 mL, 5.24 mmol) and (S)-2-piperazin-2-yl-ethanol (1.3 g, 9.99 mmol) in dimethylsulfoxide/toluene (1:2)(18 ml), stir under nitrogen and heat in an oil bath at 120° C. for 72 hours. Dilute the mixture with water (20 mL) and ethyl acetate (40 mL), separate layers and extract the aqueous with ethyl acetate. Combine all ethyl acetate extracts and wash with water and brine. Dry the organic phase (Na2SO4), filter and concentrate under reduced pressure. Purify by silica gel chromatography (eluent: 0-13% 2N ammonia in methanol/dichloromethane) to give 780 mg of impure product. Purify by silica gel chromatography (eluent: 85% dichloromethane/10% acetonitrile/0%2N ammonia in methanol to 80% dichloromethane/10% acetonitrile/10% 2N ammonia in methanol) to give the title compound (516 mg, 27%): Mass Spectrum (ESMS) 379 (M+1); 377 (M−1).
後処理
- customseparate layers
- extractionextract the aqueous with ethyl acetate
- washwash with water and brine
- dry with materialDry the organic phase (Na2SO4)
- filtrationfilter
- concentrationconcentrate under reduced pressure
- customPurify by silica gel chromatography (eluent: 0-13% 2N ammonia in methanol/dichloromethane)
出典と根拠
- ORDレコード
- ord-056780a3f2694141babfa2992ca66ad9
- 出典データセット
- uspto-grants-2008_06
- 特許番号
- US07384934B2
関連ノート
読み込み中…