Ethyl 2-amino-3-sulfanylpropanoate → (+/-)-ethyl alpha-[[[(4-chlorophenyl)[2-chloro-4-(4,5-dihydro-3,5-dioxo-1,2,4-triazin-2(3H)-yl)phenyl]methyl]thio]methyl]glycine

HRID 984045Notes

Reaction equation

HRID 984045 reaction equation
[Na].[NH2:2][CH:3]([CH2:9][SH:10])[C:4]([O:6]CC)=[O:5].[Cl:11][C:12]1[CH:13]=[C:14]([N:27]2[C:32](=[O:33])[NH:31][C:30](=[O:34])[CH:29]=[N:28]2)[CH:15]=[CH:16][C:17]=1[CH:18](Cl)[C:19]1[CH:24]=[CH:23][C:22]([Cl:25])=[CH:21][CH:20]=1.N12CCCN=C1CCC[CH2:37][CH2:36]2>C1COCC1.C(O)C>[CH2:36]([NH:2][CH:3]([CH2:9][S:10][CH:18]([C:19]1[CH:24]=[CH:23][C:22]([Cl:25])=[CH:21][CH:20]=1)[C:17]1[CH:16]=[CH:15][C:14]([N:27]2[C:32](=[O:33])[NH:31][C:30](=[O:34])[CH:29]=[N:28]2)=[CH:13][C:12]=1[Cl:11])[C:4]([OH:6])=[O:5])[CH3:37]

Participants

7

Reactant 4

HCID 3297Ethyl 2-amino-3-sulfanylpropanoateHCID 811841,8-Diazabicyclo(5.4.0)undec-7-eneHCID 5360545SodiumHCID 225573573-chloro-4-[chloro(4-chlorophenyl)methyl]phenyl-1,2,4-triazine-3,5(2H,4H)-dione

Product 1

HCID 86585301(+/-)-ethyl alpha-[[[(4-chlorophenyl)[2-chloro-4-(4,5-dihydro-3,5-dioxo-1,2,4-triazin-2(3H)-yl)phenyl]methyl]thio]methyl]glycine

Reagents, catalysts & solvents 2

HCID 702EthanolSolventHCID 8028TetrahydrofuranSolvent

Procedure

Sodium (0.075 mol) was added portionwise to ethanol (50 ml) under N2 atmosphere and this mixture was stirred until complete dissolution. Ethyl 2-amino-3-mercaptopropanoate (0.075 mol) was added and the mixture was stirred for 2 hours at RT. The solvent was evaporated, THF (50 ml) was added to the residue, and a solution of 2-[3-chloro-4-[chloro(4-chlorophenyl)methyl]phenyl]-1,2,4-triazine-3,5(2H,4H)-dione (0.015 mol) in THF (50 ml) was added. 1,8-diazabicyclo[5.4.0]undec-7-ene (0.03 mol) was added and the resulting reaction mixture was stirred overnight at RT. The solvent was evaporated. The residue was stirred in water and extracted with CH2Cl2. The organic layer was separated, washed with water, dried, filtered and the solvent was evaporated. This fraction was purified by HPLC over silica gel (eluent: CH2Cl2/CH2OH 97/3). The pure fractions were collected and the solvent was evaporated. The residue was stirred in DIPE, filtered off, washed and dried, yielding (±)-ethyl α-[[[(4-chlorophenyl)[2-chloro-4-(4,5-dihydro-3,5-dioxo-1,2,4-triazin-2(3H)-yl)phenyl]methyl]thio]methyl]glycine (compound 95).

Workup

  1. stirringthe mixture was stirred for 2 hours at RT
  2. customThe solvent was evaporated
  3. additionTHF (50 ml) was added to the residue
  4. customthe resulting reaction mixture
  5. stirringwas stirred overnight at RT
  6. customThe solvent was evaporated
  7. stirringThe residue was stirred in water
  8. extractionextracted with CH2Cl2
  9. customThe organic layer was separated
  10. washwashed with water
  11. customdried
  12. filtrationfiltered
  13. customthe solvent was evaporated
  14. customThis fraction was purified by HPLC over silica gel (eluent: CH2Cl2/CH2OH 97/3)
  15. customThe pure fractions were collected
  16. customthe solvent was evaporated
  17. stirringThe residue was stirred in DIPE
  18. filtrationfiltered off
  19. washwashed
  20. customdried

Sources & evidence

ORD record
ord-35eaf45b7e7e4182bd1df1f11857821c
Source dataset
uspto-grants-2005_03
Patent number
US06867207B2

Reaction notes

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