(Diethylamino)sulfur trifluoride → N-(1-(3-(4-Chlorophenyl)-1-fluoropentan-3-yl)-1H-indol-4-yl)methanesulfonamide

HRID 1477918Notes

Reaction equation

HRID 1477918 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]([N:14]2[C:22]3[C:17](=[C:18]([NH:23][S:24]([CH3:27])(=[O:26])=[O:25])[CH:19]=[CH:20][CH:21]=3)[CH:16]=[CH:15]2)([CH2:12][CH3:13])[CH2:9][CH2:10]O)=[CH:4][CH:3]=1.CCN(S(F)(F)[F:34])CC>C(Cl)Cl>[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]([N:14]2[C:22]3[C:17](=[C:18]([NH:23][S:24]([CH3:27])(=[O:26])=[O:25])[CH:19]=[CH:20][CH:21]=3)[CH:16]=[CH:15]2)([CH2:12][CH3:13])[CH2:9][CH2:10][F:34])=[CH:4][CH:3]=1

Participants

4

Reactant 2

HCID 123472(Diethylamino)sulfur trifluorideHCID 70560533N-(1-(3-(4-Chlorophenyl)-1-hydroxypentan-3-yl)-1H-indol-4-yl)methanesulfonamide

Product 1

HCID 70562733N-(1-(3-(4-Chlorophenyl)-1-fluoropentan-3-yl)-1H-indol-4-yl)methanesulfonamide

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of N-(1-(3-(4-chlorophenyl)-1-hydroxypentan-3-yl)-1H-indol-4-yl)methanesulfonamide (20 mg, 0.05 mmol), as described in Example 40 Step I, in DCM (5 mL) was added DAST (16 mg, 0.1 mmol) at 0° C. The mixture was stirred for 1 h, then quenched with saturated aqueous ammonium chloride (5 mL) and extracted with ethyl acetate. The combined organics were washed with water (5 mL) and brine (5 mL), dried over MgSO4, filtered and concentrated. The resulting crude product was purified by Pre-HPLC (Mobile phase: acetonitrile/water (0.03% TFA)) to afford the title racemic compound as a white solid. The racemic compound was submitted to chiral SFC separation using IC (30% MeOH (0.1% DEA)/CO2, 4.6×250 mm, 41° C.) to give two separated enantiomers. LC/MS m/z=409.1[M+H]+.

Workup

  1. customquenched with saturated aqueous ammonium chloride (5 mL)
  2. extractionextracted with ethyl acetate
  3. washThe combined organics were washed with water (5 mL) and brine (5 mL)
  4. dry with materialdried over MgSO4
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customThe resulting crude product was purified by Pre-HPLC (Mobile phase: acetonitrile/water (0.03% TFA))

Sources & evidence

ORD record
ord-8bec717bea0144d893b5194e9c36c509
Source dataset
uspto-grants-2016_08
Patent number
US09403807B2

Reaction notes

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