Hydrochloric Acid → Lurasidone hydrochloride

HRID 1480593Notes

Reaction equation

HRID 1480593 reaction equation
[CH:1]1[CH:2]=[CH:3][C:4]2[S:9][N:8]=[C:7]([N:10]3[CH2:15][CH2:14][N:13]([CH2:16][C@H:17]4[C@H:22]([CH2:23][N:24]5[C:34](=[O:35])[C@H:33]6[C@H:27]([C@H:28]7[CH2:32][C@@H:31]6[CH2:30][CH2:29]7)[C:25]5=[O:26])[CH2:21][CH2:20][CH2:19][CH2:18]4)[CH2:12][CH2:11]3)[C:5]=2[CH:6]=1.[ClH:36]>CO>[CH:1]1[CH:2]=[CH:3][C:4]2[S:9][N:8]=[C:7]([N:10]3[CH2:15][CH2:14][N:13]([CH2:16][C@H:17]4[C@H:22]([CH2:23][N:24]5[C:34](=[O:35])[C@H:33]6[C@H:27]([C@H:28]7[CH2:32][C@@H:31]6[CH2:30][CH2:29]7)[C:25]5=[O:26])[CH2:21][CH2:20][CH2:19][CH2:18]4)[CH2:12][CH2:11]3)[C:5]=2[CH:6]=1.[ClH:36]

Participants

4

Reactant 2

HCID 313Hydrochloric AcidHCID 213046Lurasidone2×

Product 1

HCID 11237860Lurasidone hydrochloride

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Conditions

Temperature
62.5 °C

Procedure

100 g lurasidone free base of Formula (H) and 3500 mL methanol were added to round bottom flask at 25° C. to 35° C. and heated to 60 to 65° C. for 10 min. To the reaction mass 14% 74.5 g isopropanolic hydrochloric acid was added and stirred for 1 hour at same temperature. The reaction mixture was charcoalized and filtered. The filtrate was distilled to remove methanol under vacuum below 45° C. The residue was again treated with 500 mL methanol at 45° C. and stirred for 30 min. The reaction mixture was cooled to 25° C. The reaction mixture was further cooled to 0 to 5° C. and stirred for 2 hours. The precipitated product was filtered and washed with 100 mL methanol to afford crystalline lurasidone hydrochloride of Formula (1). X-ray powder diffraction pattern (FIG. 1), DSC (FIG. 2).

Workup

  1. filtrationfiltered
  2. distillationThe filtrate was distilled
  3. customto remove methanol under vacuum below 45° C
  4. additionThe residue was again treated with 500 mL methanol at 45° C.
  5. stirringstirred for 30 min
  6. temperatureThe reaction mixture was cooled to 25° C
  7. temperatureThe reaction mixture was further cooled to 0 to 5° C.
  8. stirringstirred for 2 hours
  9. filtrationThe precipitated product was filtered
  10. washwashed with 100 mL methanol

Sources & evidence

ORD record
ord-f0fdad9204db4f6786adbabec5006fc7
Source dataset
uspto-grants-2016_08
Patent number
US09409899B2

Reaction notes

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