反应详情

温度

65 °C

N-hydroxy-3-[4-[[[2-(2-methyl-1H-indol-3-yl)ethyl]amino]methyl]phenyl]-2E-2-propenamide free base form HA (10.0 g) is placed in a 4-necked reaction flask with mechanical stirrer. Demineralized water (110.5 g) is added, and the suspension is heated to 65° C. (inner temperature) within 30 minutes. The DL-lactic acid solution is added to this suspension during 30 minutes at 65° C. During the addition of the lactate salt solution, the suspension converted into a solution. The addition funnel is rinsed with demineralized water (9.1 g), and the solution is stirred at 65° C. for an additional 30 minutes. The solution is cooled down to 45° C. (inner temperature) and seed crystals (10 mg N-hydroxy-3-[4-[[[2-(2-methyl-1H-indol-3-yl)ethyl]amino]methyl]phenyl]-2E-2-propenamide DL-lactate monohydrate) are added at this temperature. The suspension is cooled down to 33° C. and is stirred for an additional 20 hours at this temperature. The suspension is re-heated to 65° C., stirred for 1 hour at this temperature and is cooled to 33° C. within 1 hour. After additional stirring for 3 hours at 33° C., the product is isolated by filtration, and the filter cake is washed with demineralized water (2×20 g). The wet filter-cake is dried in vacuo at 50° C. to obtain the anhydrous N-hydroxy-3-[4-[[[2-(2-methyl-1H-indol-3-yl)ethyl]amino]methyl]phenyl]-2E-2-propenamide DL-lactate salt as a crystalline product. The product is identical to the monohydrate salt (form HA) in HPLC and in 1H-NMR, with the exception of the integrals of water signals in the 1H-NMR spectra. XRPD indicated the presence of the anhydrate form.

1. washThe addition funnel is rinsed with demineralized water (9.1 g)
2. temperatureThe solution is cooled down to 45° C. (inner temperature) and seed crystals (10 mg N-hydroxy-3-[4-[[[2-(2-methyl-1H-indol-3-yl)ethyl]amino]methyl]phenyl]-2E-2-propenamide DL-lactate monohydrate)
3. additionare added at this temperature
4. temperatureThe suspension is cooled down to 33° C.
5. stirringis stirred for an additional 20 hours at this temperature
6. temperatureThe suspension is re-heated to 65° C.
7. stirringstirred for 1 hour at this temperature
8. temperatureis cooled to 33° C. within 1 hour
9. stirringAfter additional stirring for 3 hours at 33° C.
10. customthe product is isolated by filtration
11. washthe filter cake is washed with demineralized water (2×20 g)
12. filtrationThe wet filter-cake
13. customis dried in vacuo at 50° C.