Nitrogen → (R)-tert-Butyl 3-(2-(1-(6-(N-(2,4-dimethoxybenzyl)-N-(1,2,4-thiadiazol-5-yl)sulfamoyl)-5-fluoro-2-oxobenzo[d]oxazol-3(2H)-yl)ethyl)phenyl)-3-fluoroazetidine-1-carboxylate

HRID 920262Notes

Reaction equation

HRID 920262 reaction equation
N#N.[CH3:3][O:4][C:5]1[CH:51]=[C:50]([O:52][CH3:53])[CH:49]=[CH:48][C:6]=1[CH2:7][N:8]([C:43]1[S:47][N:46]=[CH:45][N:44]=1)[S:9]([C:12]1[C:41]([F:42])=[CH:40][C:15]2[N:16]([C@@H:20]([C:22]3[CH:27]=[CH:26][CH:25]=[CH:24][C:23]=3[C:28]3(O)[CH2:31][N:30]([C:32]([O:34][C:35]([CH3:38])([CH3:37])[CH3:36])=[O:33])[CH2:29]3)[CH3:21])[C:17](=[O:19])[O:18][C:14]=2[CH:13]=1)(=[O:11])=[O:10].CCN(S(F)(F)[F:60])CC>C(Cl)Cl>[CH3:3][O:4][C:5]1[CH:51]=[C:50]([O:52][CH3:53])[CH:49]=[CH:48][C:6]=1[CH2:7][N:8]([C:43]1[S:47][N:46]=[CH:45][N:44]=1)[S:9]([C:12]1[C:41]([F:42])=[CH:40][C:15]2[N:16]([C@@H:20]([C:22]3[CH:27]=[CH:26][CH:25]=[CH:24][C:23]=3[C:28]3([F:60])[CH2:31][N:30]([C:32]([O:34][C:35]([CH3:38])([CH3:37])[CH3:36])=[O:33])[CH2:29]3)[CH3:21])[C:17](=[O:19])[O:18][C:14]=2[CH:13]=1)(=[O:10])=[O:11]

Participants

5

Reactant 3

HCID 947NitrogenHCID 123472(Diethylamino)sulfur trifluorideHCID 89526166(R)-tert-Butyl 3-(2-(1-(6-(N-(2,4-dimethoxybenzyl)-N-(1,2,4-thiadiazol-5-yl)sulfamoyl)-5-fluoro-2-oxobenzo[d]oxazol-3(2H)-yl)ethyl)phenyl)-3-hydroxyazetidine-1-carboxylate

Product 1

HCID 117629309(R)-tert-Butyl 3-(2-(1-(6-(N-(2,4-dimethoxybenzyl)-N-(1,2,4-thiadiazol-5-yl)sulfamoyl)-5-fluoro-2-oxobenzo[d]oxazol-3(2H)-yl)ethyl)phenyl)-3-fluoroazetidine-1-carboxylate

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
-78 °C

Procedure

In an oven-dried 2 dram vial under N2, added (R)-tert-butyl 3-(2-(1-(6-(N-(2,4-dimethoxybenzyl)-N-(1,2,4-thiadiazol-5-yl)sulfamoyl)-5-fluoro-2-oxobenzo[d]oxazol-3(2H)-yl)ethyl)phenyl)-3-hydroxyazetidine-1-carboxylate (32-3, 55.8 mg, 0.075 mmol) to DCM (376 μl) and cooled to −78° C. Added DAST (19.88 μl, 0.150 mmol) dropwise. After 30 min at −78° C., removed from bath and allowed to slowly warm to RT. After 20 min, LCMS showed complete consumption of SM to desired product. Cooled reaction to 0° C., slowly quenched with 3 mL H2O. Diluted with 5 mL DCM, separated layers, back-extracted aqueous with 1×5 mL DCM. Washed combined organics with 1×5 mL H2O, 1×5 mL brine. Dried combined organics over Na2SO4, filtered, concentrated to give 32-5 as a white solid. Carried crude material forward to subsequent step.

Workup

  1. customremoved from bath
  2. temperatureto slowly warm to RT
  3. waitAfter 20 min
  4. customconsumption of SM to desired product
  5. temperatureCooled
  6. customreaction to 0° C.
  7. customslowly quenched with 3 mL H2O
  8. additionDiluted with 5 mL DCM
  9. customseparated layers
  10. extractionback-extracted aqueous with 1×5 mL DCM
  11. washWashed
  12. customDried
  13. filtrationfiltered
  14. concentrationconcentrated

Sources & evidence

ORD record
ord-405478e4b63547abae8989a7204c96a8
Source dataset
uspto-grants-2016_03
Patent number
US09273040B2

Reaction notes

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