Ivabradine → Ivabradine Hydrochloride

HRID 2271382Notes

Reaction equation

HRID 2271382 reaction equation
[CH3:1][N:2]([CH2:22][C@@H:23]1[C:26]2[CH:27]=[C:28]([O:33][CH3:34])[C:29]([O:31][CH3:32])=[CH:30][C:25]=2[CH2:24]1)[CH2:3][CH2:4][CH2:5][N:6]1[C:16](=[O:17])[CH2:15][C:14]2[C:9](=[CH:10][C:11]([O:20][CH3:21])=[C:12]([O:18][CH3:19])[CH:13]=2)[CH2:8][CH2:7]1.[ClH:35].C(#N)C>C(#N)C>[CH3:1][N:2]([CH2:22][C@@H:23]1[C:26]2[CH:27]=[C:28]([O:33][CH3:34])[C:29]([O:31][CH3:32])=[CH:30][C:25]=2[CH2:24]1)[CH2:3][CH2:4][CH2:5][N:6]1[C:16](=[O:17])[CH2:15][C:14]2[C:9](=[CH:10][C:11]([O:20][CH3:21])=[C:12]([O:18][CH3:19])[CH:13]=2)[CH2:8][CH2:7]1.[ClH:35]

Participants

4

Reactant 2

HCID 132999IvabradineHCID 22261314Acetonitrile--hydrogen chloride (1/1)

Product 1

HCID 3045381Ivabradine HydrochlorideYield 75%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Conditions

Temperature
62.5 °C

Procedure

100 g of ivabradine base and 300 mL acetonitrile were cooled to 0° C. to 5° C. and acetonitrile hydrochloric acid solution was added drop wise by adjusting the pH to about 1-2. The resulting mass was stirred till complete precipitation and maintained for 60 minutes. The product was filtered under nitrogen and washed with chilled acetonitrile. The wet-cake and acetonitrile were heated at 60-65° C. and stirred for 30 min. The reaction mixture was gradually cooled to 25° C. and stirred for 1 hour. The product was filtered under vacuum and nitrogen atmosphere. The wet-cake was washed with chilled acetonitrile. The product was dried under vacuum at 50-55° C. to obtain 75% 80 g crude ivabradine hydrochloride. The product was packed in double polyethene bag under nitrogen.

Workup

  1. temperaturemaintained for 60 minutes
  2. filtrationThe product was filtered under nitrogen
  3. washwashed with chilled acetonitrile
  4. stirringstirred for 30 min
  5. temperatureThe reaction mixture was gradually cooled to 25° C.
  6. stirringstirred for 1 hour
  7. filtrationThe product was filtered under vacuum and nitrogen atmosphere
  8. washThe wet-cake was washed with chilled acetonitrile
  9. customThe product was dried under vacuum at 50-55° C.

Sources & evidence

ORD record
ord-145b19df304a427094b3575e194e6e8e
Source dataset
uspto-grants-2015_09
Patent number
US09120755B2

Reaction notes

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