(Diethylamino)sulfur trifluoride → 5-(5-Chloro-2-fluoro-phenyl)-3-[4-(2-fluoro-ethyl)-5-thiophen-2-yl-4H-[1,2,4]triazol-3-ylsulfanylmethyl]-[1,2,4]oxadiazole

HRID 732083Notes

Reaction equation

HRID 732083 reaction equation
[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([F:28])=[C:6]([C:8]2[O:12][N:11]=[C:10]([CH2:13][S:14][C:15]3[N:19]([CH2:20][CH2:21]O)[C:18]([C:23]4[S:24][CH:25]=[CH:26][CH:27]=4)=[N:17][N:16]=3)[N:9]=2)[CH:7]=1.CCN(S(F)(F)[F:35])CC>C1COCC1>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([F:28])=[C:6]([C:8]2[O:12][N:11]=[C:10]([CH2:13][S:14][C:15]3[N:19]([CH2:20][CH2:21][F:35])[C:18]([C:23]4[S:24][CH:25]=[CH:26][CH:27]=4)=[N:17][N:16]=3)[N:9]=2)[CH:7]=1

Participants

4

Reactant 2

HCID 123472(Diethylamino)sulfur trifluorideHCID 670708392-{3-[5-(5-Chloro-2-fluoro-phenyl)-[1,2,4]oxadiazol-3-ylmethylsulfanyl]-5-thiophen-2-yl-[1,2,4]triazol-4-yl}-ethanol

Product 1

HCID 670706995-(5-Chloro-2-fluoro-phenyl)-3-[4-(2-fluoro-ethyl)-5-thiophen-2-yl-4H-[1,2,4]triazol-3-ylsulfanylmethyl]-[1,2,4]oxadiazoleYield 22.7%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a cooled (−15° C.) solution of 2-{3-[5-(5-chloro-2-fluoro-phenyl)-[1,2,4]oxadiazol-3-ylmethylsulfanyl]-5-thiophen-2-yl-[1,2,4]triazol-4-yl}-ethanol (46 mg, 0.11 mmol) in anhydrous THF (15 ml) was dropwise added DAST (32 ml, 0.24 mmol). The mixture was stirred at room temperature for 1.5 h and was then quenched with MeOH (1 ml). The solvent was removed under reduced pressure and the residue was partitioned between brine and EtOAc. The aqueous layer was extracted with EtOAc (2×20 ml). The combined organic layers were washed with brine (10 ml), dried (MgSO4) and concentrated under reduced pressure. Purification by flash chromatography (EtOAc:heptane 2:1) and preparative HPLC afforded the title compound as a white solid (11 mg, 22%). 1H NMR (CDCl3) d (ppm): 8.05 (dd, 1H), 7.52 (m, 3H), 7.20 (m, 1H), 7.16 (m, 1H), 4.75 (t, 1H), 4.63 (m, 3H), 4.45 (m, 2H).

Workup

  1. customwas then quenched with MeOH (1 ml)
  2. customThe solvent was removed under reduced pressure
  3. customthe residue was partitioned between brine and EtOAc
  4. extractionThe aqueous layer was extracted with EtOAc (2×20 ml)
  5. washThe combined organic layers were washed with brine (10 ml)
  6. dry with materialdried (MgSO4)
  7. concentrationconcentrated under reduced pressure
  8. customPurification by flash chromatography (EtOAc:heptane 2:1) and preparative HPLC

Sources & evidence

ORD record
ord-d0f6b985bd574c69a6650266f9e63bc7
Source dataset
uspto-grants-2009_09
Patent number
US07585881B2

Reaction notes

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