Acetic Acid → DehydroIvabradine-d3

HRID 420868Notes

Reaction equation

HRID 420868 reaction equation
[CH3:1][O:2][C:3]1[C:19]([O:20][CH3:21])=[CH:18][C:6]2[CH2:7][C:8](=[O:17])[N:9]([CH2:12][CH2:13][CH2:14][NH:15][CH3:16])[CH:10]=[CH:11][C:5]=2[CH:4]=1.[CH3:22][O:23][C:24]1[CH:25]=[C:26]2[C:29](=[CH:30][C:31]=1[O:32][CH3:33])[CH:28]([CH:34]=O)[CH2:27]2.C(O)(=O)C.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>C1COCC1.ClCCl>[CH3:22][O:23][C:24]1[CH:25]=[C:26]2[C:29](=[CH:30][C:31]=1[O:32][CH3:33])[CH:28]([CH2:34][N:15]([CH3:16])[CH2:14][CH2:13][CH2:12][N:9]1[C:8](=[O:17])[CH2:7][C:6]3[CH:18]=[C:19]([O:20][CH3:21])[C:3]([O:2][CH3:1])=[CH:4][C:5]=3[CH:11]=[CH:10]1)[CH2:27]2

Participants

7

Reactant 4

HCID 176Acetic AcidHCID 5049666Sodium triacetoxyborohydrideHCID 593787273,4-Dimethoxybicyclo[4.2.0]octa-1,3,5-triene-7-carbaldehydeHCID 666577367,8-Dimethoxy-3-[3-(methylamino)propyl]-1,3-dihydro-2H-3-benzazepin-2-one

Product 1

HCID 46240593DehydroIvabradine-d3Yield 96.4%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
0 °C

Procedure

Dissolve 1.1 g (3.78 mmol) of 7,8-dimethoxy-3-[3-(methylamino)propyl]-1,3-dihydro-2H-3-benzazepin-2-one in 50 ml of THF and 7 ml of dichloromethane. Add 0.69 g (4.53 mmol, 1.2 equivalent) of 3,4-dimethoxybicyclo[4.2.0]octa-1,3,5-triene-7-carbaldehyde and 0.22 ml of acetic acid. Cool the reaction mixture to 0° C. and add 1.2 g (5.67 mmol, 1.5 equivalent) of sodium triacetoxyborohydride. The reaction is instantaneous. Evaporate to dryness. The residue is taken up in water, and the aqueous phase is adjusted to pH=8 by adding 20% sodium hydroxide solution and extracted with dichloromethane. The organic phase is washed with water, dried over MgSO4, filtered and evaporated to dryness. 1.7 g of an oil is obtained, which is purified by flash chromatography on 100 g of silica (eluant=dichloromethane/ethanol/NH4OH:95/5/0.5) to yield 1.4 g of title product in the form of a colourless oil.

Workup

  1. customEvaporate to dryness
  2. additionby adding 20% sodium hydroxide solution
  3. extractionextracted with dichloromethane
  4. washThe organic phase is washed with water
  5. dry with materialdried over MgSO4
  6. filtrationfiltered
  7. customevaporated to dryness

Sources & evidence

ORD record
ord-f17ee31de77848b9ba885637bed0351b
Source dataset
uspto-grants-2012_01
Patent number
US08097720B2

Reaction notes

Loading…