Glycine → Z-Glp-Pro-Gly-OH

HRID 2172170Notes

Reaction equation

HRID 2172170 reaction equation
[NH2:1][CH2:2][C:3]([OH:5])=[O:4].CN1CCOCC1.[N:13]1([C:29]([O:31][CH2:32][C:33]2[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=2)=[O:30])[C:17](=[O:18])[CH2:16][CH2:15][C@H:14]1[C:19]([N:21]1[CH2:28][CH2:27][CH2:26][C@H:22]1[C:23](O)=[O:24])=[O:20]>C(Cl)Cl>[N:13]1([C:29]([O:31][CH2:32][C:33]2[CH:34]=[CH:35][CH:36]=[CH:37][CH:38]=2)=[O:30])[C:17](=[O:18])[CH2:16][CH2:15][C@H:14]1[C:19]([N:21]1[CH2:28][CH2:27][CH2:26][C@H:22]1[C:23]([NH:1][CH2:2][C:3]([OH:5])=[O:4])=[O:24])=[O:20]

Participants

5

Reactant 3

HCID 750GlycineHCID 79724-MethylmorpholineHCID 13817306Z-Glp-Pro-OH

Product 1

HCID 131732954Z-Glp-Pro-Gly-OH

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Conditions

Temperature
25 °C

Procedure

Two solutions were prepared before the peptide coupling. Solution A: H-Gly-OH (1.2 eq.) was dissolved in MSA (3.0 eq.) at maximum 60° C. The suspension was cooled down to 25° C., diluted with DCM and stirred for at least 8 hours before being cooled to −15° C. In solution B, the carboxylic function of the Z-Glp-Pro-OH was dissolved with DCM and NMM (1.05 eq.). The solution was cooled to −15° C. The carboxylic acid was activated with IBCF (1.05 eq.) and the silylated solution A was then added to the slurry. The slurry was stirred for at least 0.5 h and left to warm to 25° C. The mixture was quenched with water and the addition of a solution of KHSO4 under stirring precipitated the peptide. The solid was filtered and washed with water. After drying under vacuum, 80% of Z-Glp-Pro-Gly-OH was recovered.

Workup

  1. temperaturebefore being cooled to −15° C
  2. temperatureThe solution was cooled to −15° C
  3. stirringThe slurry was stirred for at least 0.5 h
  4. waitleft
  5. temperatureto warm to 25° C
  6. customThe mixture was quenched with water
  7. additionthe addition of a solution of KHSO4
  8. stirringunder stirring
  9. customprecipitated the peptide
  10. filtrationThe solid was filtered
  11. washwashed with water
  12. dry with materialAfter drying under vacuum, 80% of Z-Glp-Pro-Gly-OH
  13. customwas recovered

Sources & evidence

ORD record
ord-29a656e543784974becb02ef80e04fbc
Source dataset
uspto-grants-2015_06
Patent number
US09051349B2

Reaction notes

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