Morpholine → Morpholine-4-carboxylic acid 3-[5-(2-fluorophenyl)-[1,2,4]oxadiazol-3-yl]benzoylamide

HRID 2369807Notes

Reaction equation

HRID 2369807 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]=1

Participants

4

Reactant 2

HCID 8083MorpholineHCID 578225153-[5-(2-Fluorophenyl)-[1,2,4]oxadiazol-3-yl]benzoyl isocyanate2×

Product 1

HCID 57822494Morpholine-4-carboxylic acid 3-[5-(2-fluorophenyl)-[1,2,4]oxadiazol-3-yl]benzoylamideYield 97%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

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-d5) δ 3.05 (t, 5.1 Hz, 2H), 3.46 (d, 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, 1H), 9.20 (br s, 1H); MS m/z 397.15, calcd for C20H17FN4O4 (MH+) 397.

Workup

  1. temperaturethe reaction mixture is heated
  2. temperatureto reflux for 18 h
  3. filtrationThe resulting slurry is filtered
  4. customrecrystallized from the minimum amount of dichloromethane in hexanes

Sources & evidence

ORD record
ord-4822b18b943b41d387e79d00b1b2cbb7
Source dataset
uspto-grants-2014_04
Patent number
US08710031B2

Reaction notes

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