Hydrogen Bromide → HCID 58452585, compound

HRID 70678Notes

Reaction equation

HRID 70678 reaction equation
Br.[C:2]([C:6]1[CH:11]=[CH:10][C:9](/[C:12](/[C:31]2[CH:36]=[CH:35][C:34]([S:37][CH3:38])=[C:33]([O:39]C)[N:32]=2)=[CH:13]\[C@@H:14]2[N:18](CC3C=CC(OC)=CC=3OC)[C:17](=[O:30])[CH2:16][CH2:15]2)=[CH:8][CH:7]=1)([CH3:5])([CH3:4])[CH3:3].O>O1CCOCC1>[C:2]([C:6]1[CH:11]=[CH:10][C:9](/[C:12](/[C:31]2[NH:32][C:33](=[O:39])[C:34]([S:37][CH3:38])=[CH:35][CH:36]=2)=[CH:13]\[C@H:14]2[CH2:15][CH2:16][C:17](=[O:30])[NH:18]2)=[CH:8][CH:7]=1)([CH3:5])([CH3:3])[CH3:4]

Participants

5

Reactant 3

HCID 260Hydrogen BromideHCID 962WaterHCID 67400637(5R)-5-{(E)-2-(4-tert-butylphenyl)-2-[6-methoxy-5-(methylsulfanyl)pyridin-2-yl]ethenyl}-1-(2,4-dimethoxybenzyl)pyrrolidin-2-one

Product 1

HCID 58452585HCID 58452585, compoundYield 27%

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent

Conditions

Temperature
65 °C

Procedure

48% hydrobromic acid (1.5 mL) was added to a solution of (5R)-5-{(E)-2-(4-tert-butylphenyl)-2-[6-methoxy-5-(methylsulfanyl)pyridin-2-yl]ethenyl}-1-(2,4-dimethoxybenzyl)pyrrolidin-2-one (53 mg) in 1,4-dioxane (2 mL), and the mixture was stirred at 65° C. for 30 minutes. Water was added to the reaction solution, followed by extraction with ethyl acetate. The organic layer was washed with brine and dried over anhydrous magnesium sulfate, after which the solvent was evaporated under reduced pressure. A solution of the residue in trifluoroacetic acid (4 mL) and anisole (2 mL) was stirred at 80° C. for six hours. The solvent was evaporated from the reaction solution under reduced pressure. The residue was purified by silica gel column chromatography (chloroform:methanol=100:1→3:1) and preparative HPLC (Waters Sunfire 19×150 mm 5 μm, rate: 20 mL/min, eluent: A=acetonitrile, B=0.1% trifluoroacetic acid solution, gradient: 10 to 90%) and powdered with ethyl acetate-hexane to give the title compound as a colorless powder (10 mg, 27%).

Workup

  1. extractionfollowed by extraction with ethyl acetate
  2. washThe organic layer was washed with brine
  3. dry with materialdried over anhydrous magnesium sulfate
  4. customafter which the solvent was evaporated under reduced pressure
  5. stirringA solution of the residue in trifluoroacetic acid (4 mL) and anisole (2 mL) was stirred at 80° C. for six hours
  6. customThe solvent was evaporated from the reaction solution under reduced pressure
  7. customThe residue was purified by silica gel column chromatography (chloroform:methanol=100:1→3:1) and preparative HPLC (Waters Sunfire 19×150 mm 5 μm, rate

Sources & evidence

ORD record
ord-8877bb50b7504e12851a26d50357e6e2
Source dataset
uspto-grants-2014_09
Patent number
US08822503B2

Reaction notes

Loading…