Ethyl Acetate → (S)-N-((3-Fluoro-4-(trifluoromethoxy)phenyl)(3-fluoropyridin-2-yl)methyl)-2-oxo-1,2-dihydrooxazolo[5,4-b]pyridine-5-carboxamide

HRID 2370841ノート

反応式

HRID 2370841 の反応式
[NH2:1][C:2]1[CH:3]=[CH:4][C:5]([C:9]([NH:11][C@@H:12]([C:20]2[CH:25]=[CH:24][C:23]([O:26][C:27]([F:30])([F:29])[F:28])=[C:22]([F:31])[CH:21]=2)[C:13]2[C:18]([F:19])=[CH:17][CH:16]=[CH:15][N:14]=2)=[O:10])=[N:6][C:7]=1[OH:8].Cl[C:33](Cl)([O:35]C(=O)OC(Cl)(Cl)Cl)Cl.CCOC(C)=O>C1COCC1.CCCCCC>[F:31][C:22]1[CH:21]=[C:20]([C@@H:12]([C:13]2[C:18]([F:19])=[CH:17][CH:16]=[CH:15][N:14]=2)[NH:11][C:9]([C:5]2[N:6]=[C:7]3[O:8][C:33](=[O:35])[NH:1][C:2]3=[CH:3][CH:4]=2)=[O:10])[CH:25]=[CH:24][C:23]=1[O:26][C:27]([F:28])([F:30])[F:29]

参加物

6

反応物 3

HCID 8857Ethyl AcetateHCID 94429TriphosgeneHCID 178507640HCID 178507640、化合物

生成物 1

HCID 71144268(S)-N-((3-Fluoro-4-(trifluoromethoxy)phenyl)(3-fluoropyridin-2-yl)methyl)-2-oxo-1,2-dihydrooxazolo[5,4-b]pyridine-5-carboxamide

試薬・触媒・溶媒 2

HCID 8028Tetrahydrofuran溶媒HCID 8058Hexane溶媒

反応条件

温度
-78 °C

実験手順

To a cooled (−78° C.), stirred mixture of (S)-5-amino-N-((3-fluoro-4-(trifluoromethoxy)phenyl)(3-fluoropyridin-2-yl)methyl)-6-hydroxypicolinamide (400 mg, 0.00098 mol) in THF (4 mL) was added TEA (1.31 mL, 0.0090 mol, Spectrochem, India) and triphosgene (323 mg, 0.0010 mol, Spectrochem, India) in one lot and the reaction mixture was stirred for 2 h at the same temperature. The reaction was slowly warmed to room temperature overnight. After completion of the reaction (monitored by TLC, 50% EtOAc in hexane), the reaction mixture was quenched with water (2 mL) and extracted with EtOAc (2 mL×3). The combined organic layers were dried over anhydrous sodium sulfate and purified by column chromatography, silica (60-120 mesh) using 50-60% EtOAc in petroleum ether as an eluent, and subsequently purified further using Prep TLC plates, mobile phase 50% EtOAc in hexane to give the title compound. 1H NMR (400 MHz, DMSO-d6) δ: 12.40 (s, 1H), 9.53 (d, J=7.2 Hz, 1H), 8.59 (d, J=4.4 Hz, 1H), 7.90-7.80 (m, 2H), 7.61-7.53 (m, 4H), 7.35 (d, J=8.8 Hz, 1H), 6.54 (d, J=7.2 Hz, 1H). MS (ESI, positive ion) m/z: 467.1 (M+H).

後処理

  1. stirringthe reaction mixture was stirred for 2 h at the same temperature
  2. temperatureThe reaction was slowly warmed to room temperature overnight
  3. customthe reaction mixture was quenched with water (2 mL)
  4. extractionextracted with EtOAc (2 mL×3)
  5. dry with materialThe combined organic layers were dried over anhydrous sodium sulfate
  6. custompurified by column chromatography, silica (60-120 mesh)
  7. customsubsequently purified further

出典と根拠

ORDレコード
ord-e4dad014c392432fb091ac818937d0d3
出典データセット
uspto-grants-2014_04
特許番号
US08710043B2

反応ノート

読み込み中…