Dichloromethane → (R)-5-Fluoro-3-(1-(2-(3-fluoroazetidin-3-yl)phenyl)ethyl)-2-oxo-N-(1,2,4-thiadiazol-5-yl)-2,3-dihydrobenzo[d]oxazole-6-sulfonamide

HRID 920263Notes

Reaction equation

HRID 920263 reaction equation
COC1C=C(OC)C=CC=1C[N:6]([C:41]1[S:45][N:44]=[CH:43][N:42]=1)[S:7]([C:10]1[C:39]([F:40])=[CH:38][C:13]2[N:14]([C@@H:18]([C:20]3[CH:25]=[CH:24][CH:23]=[CH:22][C:21]=3[C:26]3([F:37])[CH2:29][N:28](C(OC(C)(C)C)=O)[CH2:27]3)[CH3:19])[C:15](=[O:17])[O:16][C:12]=2[CH:11]=1)(=[O:9])=[O:8].C(Cl)Cl.C(O)(C(F)(F)F)=O>CO>[F:40][C:39]1[C:10]([S:7]([NH:6][C:41]2[S:45][N:44]=[CH:43][N:42]=2)(=[O:9])=[O:8])=[CH:11][C:12]2[O:16][C:15](=[O:17])[N:14]([C@@H:18]([C:20]3[CH:25]=[CH:24][CH:23]=[CH:22][C:21]=3[C:26]3([F:37])[CH2:27][NH:28][CH2:29]3)[CH3:19])[C:13]=2[CH:38]=1

Participants

5

Reactant 3

HCID 6344DichloromethaneHCID 6422Trifluoroacetic acidHCID 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

Product 1

HCID 89526122(R)-5-Fluoro-3-(1-(2-(3-fluoroazetidin-3-yl)phenyl)ethyl)-2-oxo-N-(1,2,4-thiadiazol-5-yl)-2,3-dihydrobenzo[d]oxazole-6-sulfonamide

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

In a 1 dram vial, added crude (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 (32-5, 25.8 mg, 0.035 mmol) to DCM (277 μl) and TFA (69.4 μl). After 15 min, diluted with 1 mL MeOH, filtered through Celite and concentrated in vacuo. Dissolved in 2 mL DMSO and purified by reverse-phase HPLC (C18 column, 5-60% 0.1% TFA/CH3CN:0.1% TFA/H2O) to give 32-6 as a white solid. 1H NMR δ (ppm) (CH3OH-d4): 8.22 (1H, s), 7.80 (1H, d, J=7.86 Hz), 7.75 (1H, d, J=5.61 Hz), 7.62 (1H, t, J=7.61 Hz), 7.56-7.44 (2H, m), 7.06 (1H, d, J=9.97 Hz), 5.49 (1H, d, J=6.64 Hz), 5.12-4.90 (2H, m), 4.81-4.61 (2H, m), 1.95 (3H, d, J=7.03 Hz). HRMS C20H18F2N5O4S2 [M+H] calc: 494.0763, obs: 494.0754.

Workup

  1. filtrationfiltered through Celite
  2. concentrationconcentrated in vacuo
  3. dissolutionDissolved in 2 mL DMSO
  4. custompurified by reverse-phase HPLC (C18 column, 5-60% 0.1% TFA/CH3CN:0.1% TFA/H2O)

Sources & evidence

ORD record
ord-4eee8536b3884cf2ac84b62af04ab414
Source dataset
uspto-grants-2016_03
Patent number
US09273040B2

Reaction notes

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