Hydrochloric Acid → Ivabradine

HRID 423132Notes

Reaction equation

HRID 423132 reaction equation
Cl.[CH3:2][O:3][C:4]1[CH:5]=[C:6]2[C:9](=[CH:10][C:11]=1[O:12][CH3:13])[C@@H:8]([CH2:14][NH:15][CH2:16][CH2:17][CH2:18][N:19]1[C:25](=[O:26])[CH2:24][C:23]3[CH:27]=[C:28]([O:33][CH3:34])[C:29]([O:31][CH3:32])=[CH:30][C:22]=3[CH2:21][CH2:20]1)[CH2:7]2.C=O.[CH3:37]C1C(Br)=C(O)C(Br)=CC=1C1(C2C=C(Br)C(O)=C(Br)C=2C)OS(=O)(=O)C2C=CC=CC1=2.Cl.C([BH3-])#N.[Na+]>CO.ClCCl>[CH3:2][O:3][C:4]1[CH:5]=[C:6]2[C:9](=[CH:10][C:11]=1[O:12][CH3:13])[C@@H:8]([CH2:14][N:15]([CH3:37])[CH2:16][CH2:17][CH2:18][N:19]1[C:25](=[O:26])[CH2:24][C:23]3[CH:27]=[C:28]([O:33][CH3:34])[C:29]([O:31][CH3:32])=[CH:30][C:22]=3[CH2:21][CH2:20]1)[CH2:7]2

Participants

8

Reactant 5

HCID 313Hydrochloric AcidHCID 712FormaldehydeHCID 6451Bromocresol GreenHCID 5003444Sodium cyanoborohydrideHCID 666726993-(3-(((7S)-3,4-dimethoxy-7-bicyclo(4.2.0)octa-1,3,5-trienyl)methylamino)propyl)-7,8-dimethoxy-2,5-dihydro-1H-3-benzazepin-4-one;hydrochloride

Product 1

HCID 132999IvabradineYield 58%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 6344DichloromethaneSolvent

Procedure

180 mg (0.36 mmol) of hydrochloride obtained in Step 1 are dissolved in a mixture of 10 mL of methanol and 5 mL of dichloromethane. To the resulting solution there are added 0.04 mL (0.54 mmol, 1.5 equivalents) of formaldehyde (37% in water) and a grain of bromocresol green. 1N aqueous hydrochloric acid solution is added until the pH is 4 (yellow-coloured solution) and then stirring is carried out at 25° C. for 30 minutes. There are then added 23 mg (0.36 mmol) of sodium cyanoborohydride, stirring is carried out at 25° C. for 12 hours whilst maintaining the pH at 4, and then evaporation to dryness is carried out. There are obtained 250 mg of an oil which is purified by flash chromatography on 100 g of silica (eluant=dichloromethane/ethanol/NH4OH: 90/10/1) to yield 100 mg of the title product in the form of a colourless oil which crystallises at ambient temperature.

Workup

  1. stirringstirring
  2. waitis carried out at 25° C. for 12 hours
  3. temperaturewhilst maintaining the pH at 4
  4. customevaporation to dryness

Sources & evidence

ORD record
ord-e802e191876048489e5ecf67bb84d89a
Source dataset
uspto-grants-2012_01
Patent number
US08101747B2

Reaction notes

Loading…