Triethylamine → N-[(1,2-Dihydro-2-oxo-3-pyridinyl)carbonyl]-L-alanyl-L-proline ethyl ester

HRID 1647387Notes

Reaction equation

HRID 1647387 reaction equation
Cl.[CH2:2]([O:4][C:5](=[O:16])[C@@H:6]1[CH2:10][CH2:9][CH2:8][N:7]1[C:11](=[O:15])[C@H:12]([CH3:14])[NH2:13])[CH3:3].C(N(CC)CC)C.[OH:24][C:25]1[N:33]=[CH:32][CH:31]=[CH:30][C:26]=1[C:27](Cl)=[O:28]>O1CCOCC1.C(Cl)(Cl)Cl>[CH2:2]([O:4][C:5](=[O:16])[C@@H:6]1[CH2:10][CH2:9][CH2:8][N:7]1[C:11](=[O:15])[C@H:12]([CH3:14])[NH:13][C:27]([C:26]1[C:25](=[O:24])[NH:33][CH:32]=[CH:31][CH:30]=1)=[O:28])[CH3:3]

Participants

6

Reactant 3

HCID 8471TriethylamineHCID 15927166L-alanyl-L-proline ethyl ester hydrochlorideHCID 178521113HCID 178521113, compound

Product 1

HCID 9862536N-[(1,2-Dihydro-2-oxo-3-pyridinyl)carbonyl]-L-alanyl-L-proline ethyl esterYield 63.4%

Reagents, catalysts & solvents 2

HCID 6212ChloroformSolventHCID 312751,4-DioxaneSolvent2×

Procedure

To a stirred solution of 4.0 g (0.016 mol) of L-alanyl-L-proline ethyl ester hydrochloride and 8 ml triethylamine in 200 ml dioxane, maintained at room temperature, a suspension of 3.0 g (0.019 mol) 2-hydroxynicotinoyl chloride in 200 ml anhydrous dioxane is added dropwise over 1 hour. After stirring for a further 3 hours at room temperature, the solvent is distilled off under reduced pressure. The crude product thus obtained is dissolved in 500 ml of chloroform and the solution washed twice with 100 ml of 5% aqueous sodium carbonate. After drying the organic layer over anhydrous magnesium sulfate, the solvent is removed on a rotary evaporator. The solid crystallizes from methylene chloride/isopropyl ether to give 3.4 g of the title compound as a white microcrystalline solid (yield: 64%).

Workup

  1. additionis added dropwise over 1 hour
  2. distillationthe solvent is distilled off under reduced pressure
  3. customThe crude product thus obtained
  4. washthe solution washed twice with 100 ml of 5% aqueous sodium carbonate
  5. dry with materialAfter drying the organic layer over anhydrous magnesium sulfate
  6. customthe solvent is removed on a rotary evaporator
  7. customThe solid crystallizes from methylene chloride/isopropyl ether

Sources & evidence

ORD record
ord-c0ebbc4a0f2e464695be431d2e6d3b24
Source dataset
uspto-grants-1995_07
Patent number
US05432159

Reaction notes

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