Ivabradine → Ivabradine

HRID 218987Notes

Reaction equation

HRID 218987 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.COC1C(OC)=CC2C(CNC)CC=2C=1>>[CH3:32][O:31][C:29]1[C:28]([O:33][CH3:34])=[CH:27][C:26]2[C@@H:23]([CH2:22][NH:2][CH3:1])[CH2:24][C:25]=2[CH:30]=1.[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

Participants

4

Reactant 2

HCID 132999IvabradineHCID 222623581-(3,4-Dimethoxybicyclo[4.2.0]octa-1,3,5-trien-7-yl)-N-methylmethanamine

Product 2

HCID 132999IvabradineHCID 11499437(S)-1-(3,4-Dimethoxybicyclo(4.2.0)octa-1,3,5-trien-7-yl)-N-methylmethanamine

Procedure

The present invention relates to a method of resolving an important intermediate of Ivabradine i.e., 4,5-dimethoxy-1-(methyl-amino-methyl)-benzocyclobutane (II) (an amine intermediate, a racemate), comprising the step of reacting a resolving agent with said intermediate to obtain the corresponding salt in an alcoholic solvent or an alcoholic aqueous solution, and crystallizing the corresponding salt to obtain the end product (1S)-4,5-dimethyloxy-1-(methylaminomethyl)-benzocyclobutane of formula (I), wherein said resolving agent is dibenzoyl-L-tartaric acid (LDBTA), dibenzoyl-D-tartaric acid (DDBTA), di-p-toluoyl-L-tartaric acid (LDTTA) or di-p-toluoyl-D-tartaric acid (DDTTA), and preferably di-p-toluoyl-L-tartaric acid, or di-p-toluoyl-D-tartaric acid.

Workup

  1. customto obtain the corresponding salt in an alcoholic solvent
  2. customan alcoholic aqueous solution, and crystallizing the corresponding salt

Sources & evidence

ORD record
ord-e6f4cf8d4f824fc6ba462ee007c830eb
Source dataset
uspto-grants-2012_06
Patent number
US08198485B2

Reaction notes

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