1-Hydroxybenzotriazole → Asp(OBn)-Pro-Thr(OBn) n-propylamide Hydrochloride

HRID 1166455Notes

Reaction equation

HRID 1166455 reaction equation
[NH:1](C(OC(C)(C)C)=O)[C@H:2]([C:14]([OH:16])=O)[CH2:3][C:4](=[O:13])[O:5][CH2:6][C:7]1[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=1.O[N:25]1[C:29]2C=CC=[CH:33][C:28]=2N=N1.[NH:34]1[CH2:55][CH2:54][CH2:53][C@H:35]1[C:36]([NH:38][C@H:39]([C:50]([OH:52])=[O:51])[C@@H:40]([CH3:49])[O:41][CH2:42][C:43]1[CH:48]=[CH:47][CH:46]=[CH:45][CH:44]=1)=[O:37].[ClH:56].C([NH-])CC.C(N(C(C)C)CC)(C)C.Cl.CN(C)CCCN=C=NCC>C(Cl)Cl.Cl.O1CCOCC1>[NH2:1][C@H:2]([C:14]([N:34]1[CH2:55][CH2:54][CH2:53][C@H:35]1[C:36]([NH:38][C@H:39]([C:50]([OH:52])=[O:51])[C@@H:40]([CH3:49])[O:41][CH2:42][C:43]1[CH:44]=[CH:45][CH:46]=[CH:47][CH:48]=1)=[O:37])=[O:16])[CH2:3][C:4](=[O:13])[O:5][CH2:6][C:7]1[CH:8]=[CH:9][CH:10]=[CH:11][CH:12]=1.[ClH:56].[CH2:29]([NH-:25])[CH2:28][CH3:33]

Participants

9

Reactant 5

HCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 1581888N-tert-Butoxycarbonyl-L-aspartic acid beta-benzyl esterHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 131724055Pro-Thr(OBn) n-propylamide Hydrochloride

Product 1

HCID 131724057Asp(OBn)-Pro-Thr(OBn) n-propylamide Hydrochloride

Reagents, catalysts & solvents 3

HCID 313Hydrochloric AcidSolventHCID 6344DichloromethaneSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
0 °C

Procedure

Commercially available Boc-L-Asp(OBn)-OH (1 g) was mixed with 1-hydroxybenzotriazole (500 mg), the title compound from Step 1 (1 g) and diisopropylethylamine (736 mg) in methylene chloride (20 mL), and the solution was cooled to 0° C. To this was added 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (710 mg) in one portion. After allowing the reaction mixture to stir at 0° C. for 5 hours, the organic solution was washed sequentially with water, 1 N 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 white solid was collected a filter plate to yield the title compound. 1H NMR (400 MHz): consistent with proposed structure.

Workup

  1. washthe organic solution was washed sequentially with water, 1 N 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 white solid was collected a filter plate

Sources & evidence

ORD record
ord-05b58a55c10e4d239719f7ce035f3764
Source dataset
uspto-grants-2003_09
Patent number
US06613880B2

Reaction notes

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