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

HRID 339993Notes

Reaction equation

[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

Participants

Conditions

Temperature: 67 °C

Procedure

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)+.

Workup

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

Sources & evidence

ORD record: ord-08054d47a9b94fecbdcead17394ab71f
Source dataset: uspto-grants-2014_11
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08895571B2

Reaction notes

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