Dimethylformamide → HCID 131732953, compound

HRID 2172169Notes

Reaction equation

HRID 2172169 reaction equation
[NH2:1][C@H:2]([C:6]([NH:8][C@H:9]([C:14]([OH:16])=[O:15])[CH2:10][CH:11]([CH3:13])[CH3:12])=[O:7])[CH:3]([CH3:5])[CH3:4].[NH:17]([C:26]([O:28][C:29]([CH3:32])([CH3:31])[CH3:30])=[O:27])[CH2:18][C:19]([NH:21][CH2:22][C:23](O)=[O:24])=[O:20].CN1CCOCC1.CN(C=O)C>CCOC(C)=O>[NH:17]([C:26]([O:28][C:29]([CH3:32])([CH3:31])[CH3:30])=[O:27])[CH2:18][C:19]([NH:21][CH2:22][C:23]([NH:1][C@H:2]([C:6]([NH:8][C@H:9]([C:14]([OH:16])=[O:15])[CH2:10][CH:11]([CH3:12])[CH3:13])=[O:7])[CH:3]([CH3:5])[CH3:4])=[O:24])=[O:20]

Participants

6

Reactant 4

HCID 6228DimethylformamideHCID 79724-MethylmorpholineHCID 3334662-(2-{[(Tert-butoxy)carbonyl]amino}acetamido)acetic acid2×HCID 6993118Valylleucine2×

Product 1

HCID 131732953HCID 131732953, compound

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent2×

Conditions

Temperature
25 °C

Procedure

On one hand, H-Val-Leu-OH (1 eq.) was added to a solution of MSA (2.72 eq.) in AcOEt. The slurry was stirred at 25° C. until a solution was obtained. The solution was then cooled to −15° C. On the other hand, Boc-Gly-Gly-OH (1.05 eq., commercially available) was added together with NMM (1.0 eq.), AcOEt and DMF. The slurry was stirred until complete dissolution and then cooled to −25° C. IBCF (1.0 eq.) was added to the Boc-Gly-Gly-OH solution to activate the carboxylic function. The silylated Val-Leu was then added and left to stir at least 30 min. The reaction mixture was conditioned to 25° C. before being quenched by the addition of water. The mixture was then diluted with AcOEt and washed with a solution of KHSO4 under stirring. The aqueous phase was discarded and the organic layer was washed again with a solution of NaCl. The organic phase was finally concentrated and the tetrapeptide crystallized under gentle stirring for at least 8 h at 5° C. The solid was recovered by filtration, once washed with cold AcOEt at 5° C. After drying under vacuum, 85% of Boc-Gly-Gly-Val-Leu-OH (SEQ ID NO 19) was recovered.

Workup

  1. customwas obtained
  2. temperatureThe solution was then cooled to −15° C
  3. stirringThe slurry was stirred until complete dissolution
  4. temperaturecooled to −25° C
  5. waitleft
  6. stirringto stir at least 30 min
  7. customwas conditioned to 25° C.
  8. custombefore being quenched by the addition of water
  9. additionThe mixture was then diluted with AcOEt
  10. washwashed with a solution of KHSO4
  11. stirringunder stirring
  12. washthe organic layer was washed again with a solution of NaCl
  13. concentrationThe organic phase was finally concentrated
  14. customthe tetrapeptide crystallized
  15. stirringunder gentle stirring for at least 8 h at 5° C
  16. filtrationThe solid was recovered by filtration
  17. washonce washed with cold AcOEt at 5° C
  18. dry with materialAfter drying under vacuum, 85% of Boc-Gly-Gly-Val-Leu-OH (SEQ ID NO 19)
  19. customwas recovered

Sources & evidence

ORD record
ord-14df14eb21e44ad8aae444b5b68cf74a
Source dataset
uspto-grants-2015_06
Patent number
US09051349B2

Reaction notes

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