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

HRID 920261Notes

Reaction equation

HRID 920261 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([OH: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:8])=[O:9])=[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([OH:37])[CH2:27][NH:28][CH2:29]3)[CH3:19])[C:13]=2[CH:38]=1

Participants

5

Reactant 3

HCID 6344DichloromethaneHCID 6422Trifluoroacetic acidHCID 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 89525960(R)-5-Fluoro-3-(1-(2-(3-hydroxyazetidin-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 (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, 60 mg, 0.081 mmol) to DCM (647 μl) and TFA (162 μl). After 15 min, diluted with 1 mL MeOH, filtered through Celite, purified by reverse-phase HPLC (20 min run, 5-60% 0.1% TFA/CH3CN:0.1% TFA/H2O) to give 32-4 as a white solid. 1H NMR δ (ppm) (CH3OH-d4): 8.21 (1H, s), 7.83 (1H, d, J=7.64 Hz), 7.71 (1H, d, J=5.61 Hz), 7.54-7.41 (2H, m), 7.27 (1H, d, J=7.61 Hz), 7.00 (1H, d, J=10.04 Hz), 5.52 (1H, dt, J=13.86, 6.77 Hz), 4.42 (2H, dd, J=10.60, 3.89 Hz), 4.14 (2H, dd, J=10.77, 3.87 Hz), 1.95 (3H, d, J=6.97 Hz). HRMS C20H19FN505S2 [M+H] calc: 492.0806, obs: 492.0796.

Workup

  1. filtrationfiltered through Celite
  2. custompurified by reverse-phase HPLC (20 min run, 5-60% 0.1% TFA/CH3CN:0.1% TFA/H2O)

Sources & evidence

ORD record
ord-c0bb4f75be744e6f83763b03975ef4d4
Source dataset
uspto-grants-2016_03
Patent number
US09273040B2

Reaction notes

Loading…