Réaction #90845

ord-39b0c928b5bb4aaa8ab300375efd17b3

Équation de réaction

NC(CO)(CO)CO
tromethamine
CCNC(=O)CCC/C=C\C[C@@H]1[C@@H](/C=C/[C@@H](O)CCc2ccccc2)[C@H](O)C[C@@H]1O
bimatoprost
NC(CO)(CO)CO
Tromethamine
CCNC(=O)CCC/C=C\C[C@@H]1[C@@H](/C=C/[C@@H](O)CCc2ccccc2)[C@H](O)C[C@@H]1O
Bimatoprost
→
CCNC(=O)CCC/C=C\C[C@@H]1[C@@H](/C=C/[C@@H](O)CCc2ccccc2)[C@H](O)C[C@@H]1O.NC(CO)(CO)CO
Bimatoprost Tromethamine

Réactifs

NC(CO)(CO)CO
tromethamine
CCNC(=O)CCC/C=C\C[C@@H]1[C@@H](/C=C/[C@@H](O)CCc2ccccc2)[C@H](O)C[C@@H]1O
bimatoprost
NC(CO)(CO)CO
Tromethamine
CCNC(=O)CCC/C=C\C[C@@H]1[C@@H](/C=C/[C@@H](O)CCc2ccccc2)[C@H](O)C[C@@H]1O
Bimatoprost

Réactifs

Aucun

Conditions de réaction

Température
-20°CELSIUS
Conditions détaillées
See reaction.notes.procedure_details.

Traitement

  1. 1
    Autredrying (
  2. 2
    workup.ADDITIONa mixture of tert-butanol/water (50/50 v/v) as solvent),
  3. 3
    Autrerotary evaporation
  4. 4
    Autrequenching the melt
  5. 5
    AutreThe most suitable method, quenching the melt
  6. 6
    Autrewas selected for the preparation of the amorphous material
  7. 7
    Températurethe temperature was maintained for 10 minutes
  8. 8
    AutreThe samples were quenched in air
  9. 9
    Autreto obtain an amorphous glass
  10. 10
    Autrewas determined at ca. 29° C. by modulated differential scanning calorimetry (MDSC)

Mode opératoire

Attempts were made to prepare amorphous tromethamine salt of bimatoprost acid by freeze drying (using a mixture of tert-butanol/water (50/50 v/v) as solvent), rotary evaporation and quenching the melt. The most suitable method, quenching the melt, was selected for the preparation of the amorphous material, followed by characterization before using this material as input material for the polymorphism study. In an attempt, Tromethamine Salt of Bimatoprost acid was heated in a vacuum oven at 120° C., the temperature was maintained for 10 minutes to melt the product. The samples were quenched in air and then cooled to −20° C. (freezer) to obtain an amorphous glass. The glass transition (Tg) was determined at ca. 29° C. by modulated differential scanning calorimetry (MDSC).

Source

DOI: 10.6084/m9.figshare.5104873.v1Brevet: US09447014B2uspto-grants-2016_09