3-Methoxy-4-(oxazol-5-yl)aniline → Merimepodib

HRID 1984969Notes

Reaction equation

HRID 1984969 reaction equation
C1(O[C:8](=[O:26])[NH:9][C:10]2[CH:15]=[CH:14][CH:13]=[C:12]([CH2:16][NH:17][C:18]([O:20][C@H:21]3[CH2:25][CH2:24][O:23][CH2:22]3)=[O:19])[CH:11]=2)C=CC=CC=1.[CH3:27][O:28][C:29]1[CH:30]=[C:31]([NH2:40])[CH:32]=[CH:33][C:34]=1[C:35]1[O:39][CH:38]=[N:37][CH:36]=1>>[CH3:27][O:28][C:29]1[CH:30]=[C:31]([NH:40][C:8](=[O:26])[NH:9][C:10]2[CH:11]=[C:12]([CH:13]=[CH:14][CH:15]=2)[CH2:16][NH:17][C:18](=[O:19])[O:20][C@H:21]2[CH2:25][CH2:24][O:23][CH2:22]2)[CH:32]=[CH:33][C:34]=1[C:35]1[O:39][CH:38]=[N:37][CH:36]=1

Participants

3

Reactant 2

HCID 154627323-Methoxy-4-(oxazol-5-yl)anilineHCID 17748134(S)-Tetrahydrofuran-3-yl (3-((phenoxycarbonyl)amino)benzyl)carbamate

Product 1

HCID 153241MerimepodibYield 91.7%

Procedure

Added 15 g of {3-[((S)-tetrahydro-furan-3-yloxycarbonylamino)-methyl]-phenyl}-carbamic acid phenyl ester 2e and 8.58 g of 3-methoxy-4-(oxazol-5-yl)benzenamine 2g into a 500 ml 3-necked flask and then purged the system with nitrogen before adding 225 ml of ethyl acetate. Next added 5.43 g of diisopropylethylamine over 1 minute, then heated at reflux for 24 hours. Once the reaction was complete, the mixture was cooled to room temperature and stirred for an additional 1 hour. Precipitated solid was filtered, washed with 45 ml of EtOAc 2 times, then dried at 58° C. for 18 hours (until a LOD is achieved of less than 1%) to give 17.46 g of crude (S)-tetrahydrofuran-3-yl 3-(3-(3-methoxy-4-(oxazol-5-yl)phenyl)ureido)benzylcarbamate 2h (90.4% yield, 98.46% a/a) as a white crystalline solid.

Workup

  1. custompurged the system with nitrogen
  2. additionbefore adding 225 ml of ethyl acetate
  3. additionNext added 5.43 g of diisopropylethylamine over 1 minute
  4. temperatureheated
  5. temperatureat reflux for 24 hours
  6. customPrecipitated solid
  7. filtrationwas filtered
  8. washwashed with 45 ml of EtOAc 2 times
  9. customdried at 58° C. for 18 hours (until a LOD

Sources & evidence

ORD record
ord-3ccb1774ab054b338c2ba157fb5c8143
Source dataset
uspto-grants-2009_06
Patent number
US07544810B2

Reaction notes

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