Lactic Acid → Panobinostat lactate

HRID 1669595Notes

Reaction equation

HRID 1669595 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 free base form HA (2θ 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 (2θ mg of N-hydroxy-3-[4-[[[2-(2-methyl-1H-indol-3-yl)ethyl]amino]methyl]phenyl]-2E-2-propenamide DL-lactate salt, anhydrate form) are added at 38° C. After stirring at 38° C. for an 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 an 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 DL-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 (2θ mg of N-hydroxy-3-[4-[[[2-(2-methyl-1H-indol-3-yl)ethyl]amino]methyl]phenyl]-2E-2-propenamide DL-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 an 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-7a9febb8f14a4ead96a0e39c11c6cf1d
Source dataset
uspto-grants-2011_08
Patent number
US07989494B2

Reaction notes

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