Lactic Acid → Panobinostat lactate

HRID 1669862Notes

Reaction equation

HRID 1669862 reaction equation
[OH:1][NH:2][C:3](=[O:26])/[CH:4]=[CH:5]/[C:6]1[CH:11]=[CH:10][C:9]([CH2:12][NH:13][CH2:14][CH2:15][C:16]2[C:24]3[C:19](=[CH:20][CH:21]=[CH:22][CH:23]=3)[NH:18][C:17]=2[CH3:25])=[CH:8][CH:7]=1.[C:27]([OH:32])(=[O:31])[CH:28]([CH3:30])[OH:29]>C(O)C.O>[C:27]([OH:32])(=[O:31])[CH:28]([CH3:30])[OH:29].[OH:1][NH:2][C:3](=[O:26])/[CH:4]=[CH:5]/[C:6]1[CH:11]=[CH:10][C:9]([CH2:12][NH:13][CH2:14][CH2:15][C:16]2[C:24]3[C:19](=[CH:20][CH:21]=[CH:22][CH:23]=3)[NH:18][C:17]=2[CH3:25])=[CH:8][CH:7]=1

Participants

4

Reactant 2

HCID 612Lactic AcidHCID 6918837Panobinostat

Product 1

HCID 23725423Panobinostat lactate

Reagents, catalysts & solvents 1

HCID 19096565Water ethanolSolvent

Conditions

Temperature
60 °C

Procedure

N-hydroxy-3-[4-[[[2-(2-methyl-1H-indol-3-yl)ethyl]amino]methyl]phenyl]-2E-2-propenamide (20 g) is placed in a 1 L glass reactor, and ethanol/water (209.4 g of a 1:1 w/w mixture) is added. The light yellow suspension is heated to 60° C. (inner temperature) within 30 minutes, and the lactic acid solution is added during 30 minutes at this temperature. The addition funnel is rinsed with water (10 g). The solution is cooled to 38° C. within 2 hours, and seed crystals (20 mg of N-hydroxy-3-[4-[[[2-(2-methyl-1H-indol-3-yl)ethyl]amino]methyl]phenyl]-2E-2-propenamide lactate salt, anhydrate form) are added at 38° C. After stirring at 38° C. for additional 2 hours, the mixture is cooled down to 25° C. within 6 hours. Cooling is continued from 25° C. to 10° C. within 5 hours, from 10° C. to 5° C. within 4 hours and from 5° C. to 2° C. within 1 hour. The suspension is stirred for additional 2 hours at 2° C., and the product is isolated by filtration. The wet filter cake is washed with water (2×30 g), and the product is dried in vacuo at 45° C. to obtain crystalline anhydrous N-hydroxy-3-[4-[[[2-(2-methyl-1H-indol-3-yl)ethyl]amino]methyl]phenyl]-2E-2-propenamide lactate salt (form A).

Workup

  1. washThe addition funnel is rinsed with water (10 g)
  2. temperatureThe solution is cooled to 38° C. within 2 hours
  3. additionseed crystals (20 mg of N-hydroxy-3-[4-[[[2-(2-methyl-1H-indol-3-yl)ethyl]amino]methyl]phenyl]-2E-2-propenamide lactate salt, anhydrate form) are added at 38° C
  4. temperaturethe mixture is cooled down to 25° C. within 6 hours
  5. temperatureCooling
  6. waitis continued from 25° C. to 10° C. within 5 hours, from 10° C. to 5° C. within 4 hours and from 5° C. to 2° C. within 1 hour
  7. stirringThe suspension is stirred for additional 2 hours at 2° C.
  8. customthe product is isolated by filtration
  9. washThe wet filter cake is washed with water (2×30 g)
  10. customthe product is dried in vacuo at 45° C.

Sources & evidence

ORD record
ord-9b8e543c23634000b6a2237cc8a211cf
Source dataset
uspto-grants-2011_08
Patent number
US07989639B2

Reaction notes

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