(Diethylamino)sulfur trifluoride → HCID 178425791, compound

HRID 1488070Notes

Reaction equation

HRID 1488070 reaction equation
O[C:2]1([C:6]2[NH:7][C:8]([C:12]3[CH:13]=[C:14]([CH:29]=[CH:30][C:31]=3[CH3:32])[C:15]([N:17]3[CH2:20][CH:19]([C:21]4[CH:28]=[CH:27][C:24]([C:25]#[N:26])=[CH:23][CH:22]=4)[CH2:18]3)=[O:16])=[C:9]([CH3:11])[N:10]=2)[CH2:5][O:4][CH2:3]1.CCN(S(F)(F)[F:39])CC>ClCCl>[F:39][C:2]1([C:6]2[NH:7][C:8]([C:12]3[CH:13]=[C:14]([CH:29]=[CH:30][C:31]=3[CH3:32])[C:15]([N:17]3[CH2:20][CH:19]([C:21]4[CH:28]=[CH:27][C:24]([C:25]#[N:26])=[CH:23][CH:22]=4)[CH2:18]3)=[O:16])=[C:9]([CH3:11])[N:10]=2)[CH2:5][O:4][CH2:3]1

Participants

4

Reactant 2

HCID 123472(Diethylamino)sulfur trifluorideHCID 178425793HCID 178425793, compound2×

Product 1

HCID 178425791HCID 178425791, compoundYield 8%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

Into a 50-mL three neck round-bottom flask, which was purged and maintained with an inert atmosphere of nitrogen, was placed a solution of 4-(1-(3-(2-(3-hydroxyoxetan-3-yl)-4-methyl-1H-imidazol-5-yl)-4-methylbenzoyl)azetidin-3-yl)benzonitrile (compound 192, 200 mg, 0.47 mmol) in dichloromethane (5 mL). This was followed by the addition of a solution of DAST (76.2 μL, 0.58 mmol) in dichloromethane (1 mL) dropwise at −78° C. The resulting solution was stirred for 1 h at room temperature, then quenched by the addition of 2 mL of sodium bicarbonate (sat.). The resulting solution was diluted with 60 mL of EtOAc and additional water. The organic layer was dried over anhydrous sodium sulfate and concentrated under reduced pressure. The residue was purified by silica gel chromatography with ethyl acetate as eluent. The crude product (50 mg) was purified by Prep-HPLC with the following conditions (Prep-HPLC-020): Column, SunFire Prep C18 OBD Column, 5 μm, 19*150 mm; mobile phase, WATER WITH 0.05% TFA and MeCN (18.0% MeCN up to 28.0% in 9 min, up to 100.0% in 2 min, down to 18.0% in 1 min); Detector, Waters 2489, 254 and 220 nm. This resulted in 15.1 mg (8%) of the title compound as a white solid. m/z (ES+) 431 (M+H)+.

Workup

  1. customInto a 50-mL three neck round-bottom flask, which was purged
  2. temperaturemaintained with an inert atmosphere of nitrogen
  3. customquenched by the addition of 2 mL of sodium bicarbonate (sat.)
  4. additionThe resulting solution was diluted with 60 mL of EtOAc and additional water
  5. dry with materialThe organic layer was dried over anhydrous sodium sulfate
  6. concentrationconcentrated under reduced pressure
  7. customThe residue was purified by silica gel chromatography with ethyl acetate as eluent
  8. customThe crude product (50 mg) was purified by Prep-HPLC with the following conditions (Prep-HPLC-020)
  9. waitmobile phase, WATER WITH 0.05% TFA and MeCN (18.0% MeCN up to 28.0% in 9 min
  10. waitup to 100.0% in 2 min
  11. waitdown to 18.0% in 1 min)

Sources & evidence

ORD record
ord-7face50af54044f295ad0b1ecc6a08cb
Source dataset
uspto-grants-2016_08
Patent number
US09428502B2

Reaction notes

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