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

HRID 339993노트

반응식

HRID 339993 반응식
[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

참가 물질

7

반응물 4

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

생성물 1

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

시약·촉매·용매 2

HCID 8857Ethyl Acetate용매HCID 312751,4-Dioxane용매

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온도
67 °C

실험 절차

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)+.

후처리

  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

출처 및 근거

ORD 기록
ord-08054d47a9b94fecbdcead17394ab71f
출처 데이터셋
uspto-grants-2014_11
특허 번호
US08895571B2

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