Diisopropylethylamine → 2-bromo-6-[(1S)-1-(3-fluorobenzyl)-2-hydroxyethyl]-6,7-dihydro-5H-pyrrolo[3,4-b]pyridin-5-one

HRID 339993ノート

反応式

HRID 339993 の反応式
[Br:1][C:2]1[CH:12]=[CH:11][C:5]([C:6]([O:8]CC)=O)=[C:4]([CH2:13]Br)[N:3]=1.[NH2:15][C@@H:16]([CH2:19][C:20]1[CH:25]=[CH:24][CH:23]=[C:22]([F:26])[CH:21]=1)[CH2:17][OH:18].C(N(CC)C(C)C)(C)C.C([O-])(O)=O.[Na+]>CCOC(C)=O.O1CCOCC1>[Br:1][C:2]1[N:3]=[C:4]2[CH2:13][N:15]([C@@H:16]([CH2:19][C:20]3[CH:25]=[CH:24][CH:23]=[C:22]([F:26])[CH:21]=3)[CH2:17][OH:18])[C:6](=[O:8])[C:5]2=[CH:11][CH:12]=1

参加物

7

反応物 4

HCID 81531DiisopropylethylamineHCID 516892Sodium BicarbonateHCID 46911825(S)-2-Amino-3-(3-fluorophenyl)propan-1-olHCID 86681480Ethyl 6-bromo-2-(bromomethyl)nicotinate

生成物 1

HCID 866814792-bromo-6-[(1S)-1-(3-fluorobenzyl)-2-hydroxyethyl]-6,7-dihydro-5H-pyrrolo[3,4-b]pyridin-5-one

試薬・触媒・溶媒 2

HCID 8857Ethyl Acetate溶媒HCID 312751,4-Dioxane溶媒

反応条件

温度
67 °C

実験手順

Ethyl 6-bromo-2-(bromomethyl)nicotinate (0.17 g, 0.53 mmol), (2S)-2-amino-3-(3-fluorophenyl)propan-1-ol (0.11 g, 0.64 mmol), N,N-diisopropylethylamine (0.2 g, 2 mmol) and 1,4-dioxane (5 mL) were mixed in one 20 mL microwave tube, and the mixture was stirred at 67° C. for overnight. LC-MS showed most starting material was converted to Br-replacement product. Then the temperature was raised to 125° C. for 45 mins, cooled to room temperature, then worked up with EtOAc and aqueous NaHCO3 solution, extracted twice with EtOAc and dried over sodium sulfate, and concentrated under reduced pressure. Purification by combi-flash chromatography gave the desired product. LC-MS found: 365.1 (M+H)+.

後処理

  1. temperatureThen the temperature was raised to 125° C. for 45 mins
  2. temperaturecooled to room temperature
  3. extractionextracted twice with EtOAc
  4. dry with materialdried over sodium sulfate
  5. concentrationconcentrated under reduced pressure
  6. customPurification by combi-flash chromatography

出典と根拠

ORDレコード
ord-08054d47a9b94fecbdcead17394ab71f
出典データセット
uspto-grants-2014_11
特許番号
US08895571B2

反応ノート

読み込み中…