Iodine → HCID 71548841, compound

HRID 1526521Notes

Reaction equation

HRID 1526521 reaction equation
II.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C(N(CC)CC)C.[CH2:29]([C:36]1([C:51]([NH:53][NH:54][C:55]([C:57]2[CH:62]=[C:61]([O:63][CH3:64])[CH:60]=[C:59]([O:65][CH3:66])[CH:58]=2)=[O:56])=O)[C:40](=[O:41])[N:39]([C@@H:42]([C:44]2[CH:49]=[CH:48][CH:47]=[CH:46][CH:45]=2)[CH3:43])[C:38](=[O:50])[NH:37]1)[C:30]1[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=1.C(=O)([O-])O.[Na+].S([O-])([O-])(=O)=S.[Na+].[Na+]>ClCCl>[CH2:29]([C@:36]1([C:51]2[O:56][C:55]([C:57]3[CH:62]=[C:61]([O:63][CH3:64])[CH:60]=[C:59]([O:65][CH3:66])[CH:58]=3)=[N:54][N:53]=2)[NH:37][C:38](=[O:50])[N:39]([C@@H:42]([C:44]2[CH:49]=[CH:48][CH:47]=[CH:46][CH:45]=2)[CH3:43])[C:40]1=[O:41])[C:30]1[CH:31]=[CH:32][CH:33]=[CH:34][CH:35]=1

Participants

8

Reactant 6

HCID 807IodineHCID 8471TriethylamineHCID 11776TriphenylphosphineHCID 24477Sodium ThiosulfateHCID 516892Sodium BicarbonateHCID 89509950HCID 89509950, compound

Product 1

HCID 71548841HCID 71548841, compound

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

To a stirring solution of iodine (354 mg, 1.394 mmol) in dichloromethane (8 mL) was added triphenylphosphine (375 mg, 1.429 mmol). After 5 min triethylamine (0.389 mL, 2.79 mmol) was added. After 5 min a solution of the product from Step A (180 mg, 0.348 mmol) in dichloromethane (3 mL) was added. After stirring at ambient temperature for 1 h, a 1:1 mixture of saturated aqueous sodium hydrogen carbonate and saturated aqueous sodium thiosulfate (5 mL) was added. The biphasic mixture was stirred for 10 min, the layers were separated and the aqueous phase extracted with dichloromethane (3×5 mL). The combined organic phases were washed with saturated aqueous brine (1×5 mL), dried with anhydrous sodium sulfate, filtered and the solvent removed in vacuo. The residue was purified by column chromatography (silica gel 40 g column) eluting with ethyl acetate/hexane (gradient from 0% to 100%) to give a mixture of diastereomers as a colorless amorphous solid. The isomers were separated via chiral HPLC (ChiralPak AS-H; 40% 2:1 methanol:acetonitrile/carbon dioxide) to afford the first eluting isomer (5R)-5-Benzyl-5-[5-(3,5-dimethoxyphenyl)-1,3,4-oxadiazol-2-yl]-3-[(1R)-1-phenylethyl]imidazolidine-2,4-dione (2.25 minutes) and the second eluting isomer (5S)-5-Benzyl-5-[5-(3,5-dimethoxyphenyl)-1,3,4-oxadiazol-2-yl]-3-[(1R)-1-phenylethyl]imidazolidine-2,4-dione (3.45 minutes) as colorless amorphous solids. LC/MS 499.1 (M+1). IC50 value=C rating for the title compound.

Workup

  1. additionwas added
  2. stirringThe biphasic mixture was stirred for 10 min
  3. customthe layers were separated
  4. extractionthe aqueous phase extracted with dichloromethane (3×5 mL)
  5. washThe combined organic phases were washed with saturated aqueous brine (1×5 mL)
  6. dry with materialdried with anhydrous sodium sulfate
  7. filtrationfiltered
  8. customthe solvent removed in vacuo
  9. customThe residue was purified by column chromatography (silica gel 40 g column)
  10. washeluting with ethyl acetate/hexane (gradient from 0% to 100%)
  11. customto give
  12. additiona mixture of diastereomers as a colorless amorphous solid
  13. customThe isomers were separated via chiral HPLC (ChiralPak AS-H; 40% 2:1 methanol:acetonitrile/carbon dioxide)

Sources & evidence

ORD record
ord-52a7e08470e24790ab082975ff9176d8
Source dataset
uspto-grants-2015_07
Patent number
US09085568B2

Reaction notes

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