Morpholine → Morpholine-4-carboxylic acid 3-[5-(2-fluorophenyl)-[1,2,4]oxadiazol-3-yl]benzoylamide
Reaction equation
[NH:1]1[CH2:6][CH2:5][O:4][CH2:3][CH2:2]1.[F:7][C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][C:9]=1[C:14]1[O:18][N:17]=[C:16]([C:19]2[CH:20]=[C:21]([CH:27]=[CH:28][CH:29]=2)[C:22]([N:24]=[C:25]=[O:26])=[O:23])[N:15]=1>ClCCl>[F:7][C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][C:9]=1[C:14]1[O:18][N:17]=[C:16]([C:19]2[CH:20]=[C:21]([CH:27]=[CH:28][CH:29]=2)[C:22]([NH:24][C:25]([N:1]2[CH2:6][CH2:5][O:4][CH2:3][CH2:2]2)=[O:26])=[O:23])[N:15]=1Participants
Procedure
Morpholine (114 μL; 1.30 mmol, 2.0 eq.) is added to a solution of 3-[5-(2-fluorophenyl)-[1,2,4]oxadiazol-3-yl]benzoyl isocyanate (Compound A4, 200 mg, 0.65 mmol) in anhydrous dichloromethane (4.0 mL) under nitrogen, and the reaction mixture is heated to reflux for 18 h. The resulting slurry is filtered and recrystallized from the minimum amount of dichloromethane in hexanes to afford 249 mg (97%) of morpholine-4-carboxylic acid 3-[5-(2-fluorophenyl)-[1,2,4]oxadiazol-3-yl]benzoylamide (Compound 25) as a white powder: mp 190-194° C.; 1H NMR (300 MHz, DMSO-d6) δ 3.05 (t, J=5.1 Hz, 2H), 3.46 (d, J=4.5 Hz, 2H), 3.61 (m, 2H), 3.76 (t, J=5.1 Hz, 2H), 7.46-7.90 (m, 4H), 7.59 (d, J=8.1 Hz, 1H), 8.22-8.29 (m, 2H), 8.53 (d, J=1.5 Hz, 1 H), 9.20 (br s, 1H); MS m/z 397.15, calcd for C20H17FN4O4 (MH+) 397.
Workup
- temperaturethe reaction mixture is heated
- temperatureto reflux for 18 h
- filtrationThe resulting slurry is filtered
- customrecrystallized from the minimum amount of dichloromethane in hexanes
Sources & evidence
- ORD record
- ord-201bab8d90854e018a6b189b8655b502
- Source dataset
- uspto-grants-2016_03
- Patent number
- US09273076B2
Reaction notes
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