Propylamine → Pro-Thr(OBn) n-propylamide Hydrochloride

HRID 1166454Notes

Reaction equation

HRID 1166454 reaction equation
[NH:1]([C:16]([O:18]C(C)(C)C)=O)[C@H:2]([C:13]([OH:15])=[O:14])[C@@H:3]([CH3:12])[O:4][CH2:5][C:6]1[CH:11]=[CH:10][CH:9]=[CH:8][CH:7]=1.ON1C2C=[CH:30][CH:31]=[CH:32][C:27]=2[N:26]=N1.C(N(C(C)C)CC)(C)C.[ClH:42].C[N:44](C)[CH2:45][CH2:46][CH2:47]N=C=NCC.C(N)CC>C(Cl)Cl.Cl.O1CCOCC1>[NH:26]1[CH2:27][CH2:32][CH2:31][C@H:30]1[C:16]([NH:1][C@H:2]([C:13]([OH:15])=[O:14])[C@@H:3]([CH3:12])[O:4][CH2:5][C:6]1[CH:7]=[CH:8][CH:9]=[CH:10][CH:11]=1)=[O:18].[ClH:42].[CH2:45]([NH-:44])[CH2:46][CH3:47]

Participants

9

Reactant 5

HCID 7852PropylamineHCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 1549483L-Threonine, N-[(1,1-dimethylethoxy)carbonyl]-O-(phenylmethyl)-HCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochloride

Product 1

HCID 131724055Pro-Thr(OBn) n-propylamide Hydrochloride

Reagents, catalysts & solvents 3

HCID 313Hydrochloric AcidSolvent2×HCID 6344DichloromethaneSolventHCID 312751,4-DioxaneSolvent2×

Conditions

Temperature
0 °C

Procedure

Commercially available Boc-L-Thr(OBn)-OH (5 g) was mixed with 1-hydroxybenzotriazole (2.62 g), diisopropylethylamine (2.08 g) in methylene chloride (14 mL) and cooled to 0° C. To this was added 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride, followed by n-propylamine (1.14 g) 2 minutes later. After allowing the reaction mixture to stir at 0 for 5 hours, the organic solution was washed sequentially with water, 1N hydrochloric acid, 5% sodium bicarbonate, then dried (magnesium sulfate), filtered and evaporated to obtain an oily residue. This residue was taken up in 4M hydrogen chloride in dioxane solution (50 mL) and allowed to stand at room temperature for 30 minutes. The solvent was then evaporated and the product triturated with ether. The resulting solid was collected a filter plate. A portion of this material (1.5 g) was then mixed with Boc-L-Pro-OSu (1.5 g) in methylene chloride (20 mL), cooled to 0° C., and diisopropylethylamine (675 mg) was added. After allowing the reaction mixture to stir at 0° C. for 5 hours, the organic solution was washed sequentially with water, 1N hydrochloric acid, 5% sodium bicarbonate, then dried (magnesium sulfate), filtered and evaporated to obtain an oily residue. This residue was taken up in 4 M hydrogen chloride in dioxane solution (50 mL) and allowed to stand at room temperature for 30 minutes. The solvent was then evaporated and the product triturated with ether. The resulting solid was collected a filter plate to yield the title compound (1.45 g). 1H NMR (400 MHz): consistent with proposed structure.

Workup

  1. washthe organic solution was washed sequentially with water, 1N hydrochloric acid, 5% sodium bicarbonate
  2. dry with materialdried (magnesium sulfate)
  3. filtrationfiltered
  4. customevaporated
  5. customto obtain an oily residue
  6. waitto stand at room temperature for 30 minutes
  7. customThe solvent was then evaporated
  8. customthe product triturated with ether
  9. customThe resulting solid was collected a filter plate
  10. additionA portion of this material (1.5 g) was then mixed with Boc-L-Pro-OSu (1.5 g) in methylene chloride (20 mL)
  11. temperaturecooled to 0° C.
  12. additiondiisopropylethylamine (675 mg) was added
  13. stirringto stir at 0° C. for 5 hours
  14. washthe organic solution was washed sequentially with water, 1N hydrochloric acid, 5% sodium bicarbonate
  15. dry with materialdried (magnesium sulfate)
  16. filtrationfiltered
  17. customevaporated
  18. customto obtain an oily residue
  19. waitto stand at room temperature for 30 minutes
  20. customThe solvent was then evaporated
  21. customthe product triturated with ether
  22. customThe resulting solid was collected a filter plate

Sources & evidence

ORD record
ord-f8c51a61f21f42e386ec9ccdad28b689
Source dataset
uspto-grants-2003_09
Patent number
US06613880B2

Reaction notes

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