Ethyl orthoformate → HCID 51030866, compound

HRID 706270Notes

Reaction equation

HRID 706270 reaction equation
[NH2:1][C:2]1[CH:3]=[C:4]([N:9]2[C@@H:13]([C:14]3[CH:19]=[CH:18][C:17]([O:20][CH3:21])=[CH:16][CH:15]=3)[C@@H:12]([CH3:22])[N:11](CC3C=CC(OC)=CC=3)[C:10]2=[O:32])[CH:5]=[CH:6][C:7]=1[NH2:8].[CH:33](OCC)(OCC)OCC>>[NH:1]1[C:2]2[CH:3]=[C:4]([N:9]3[C@@H:13]([C:14]4[CH:19]=[CH:18][C:17]([O:20][CH3:21])=[CH:16][CH:15]=4)[C@@H:12]([CH3:22])[NH:11][C:10]3=[O:32])[CH:5]=[CH:6][C:7]=2[N:8]=[CH:33]1

Participants

3

Reactant 2

HCID 31214Ethyl orthoformateHCID 57488457HCID 57488457, compound

Product 1

HCID 51030866HCID 51030866, compound

Procedure

(4R,5S)-1-(3,4-diaminophenyl)-3-(4-methoxybenzyl)-5-(4-methoxyphenyl)-4-methylimidazolidin-2-one (0.105 g, 0.24 mmol) obtained from step F was dissolved in 3 mL triethyl orthoformate. The reaction was stirred for 30 minutes at reflux. After cooling the solvent was removed and the remains were dissolved in 8 mL trifluoroacetic acid. The reaction was stirred for 14 hours at ambient temperature. The TFA was removed under reduced pressure and the residue was re-dissolved in 20 mL of buffer (pH7) and three times extracted by means of 25 mL dichloromethane. The combined organic layers were washed with brine, dried over sodium sulfate, filtrated and the solvent was removed under reduced pressure. The final product was purified by FPLC using a chloroform-methanol gradient (0→10%). The product elutes at about 5% methanol.

Workup

  1. temperatureat reflux
  2. temperatureAfter cooling the solvent
  3. customwas removed
  4. dissolutionthe remains were dissolved in 8 mL trifluoroacetic acid
  5. stirringThe reaction was stirred for 14 hours at ambient temperature
  6. customThe TFA was removed under reduced pressure
  7. dissolutionthe residue was re-dissolved in 20 mL of buffer (pH7) and three times
  8. extractionextracted by means of 25 mL dichloromethane
  9. washThe combined organic layers were washed with brine
  10. dry with materialdried over sodium sulfate
  11. filtrationfiltrated
  12. customthe solvent was removed under reduced pressure
  13. customThe final product was purified by FPLC

Sources & evidence

ORD record
ord-e470237bd19f428ea490dd1eebd4b825
Source dataset
uspto-grants-2015_11
Patent number
US09173885B2

Reaction notes

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