Amlodipine → HCID 85048726, compound

HRID 1019019Notes

Reaction equation

HRID 1019019 reaction equation
[CH3:1][CH:2]([C:4]1[N:8]([CH2:9][CH2:10][C@@H:11]([OH:19])[CH2:12][C@@H:13]([OH:18])[CH2:14][C:15]([OH:17])=[O:16])[C:7]([C:20]2[CH:21]=[CH:22][C:23]([F:26])=[CH:24][CH:25]=2)=[C:6]([C:27]2[CH:28]=[CH:29][CH:30]=[CH:31][CH:32]=2)[C:5]=1[C:33]([NH:35][C:36]1[CH:37]=[CH:38][CH:39]=[CH:40][CH:41]=1)=[O:34])[CH3:3].[CH3:42][CH2:43][O:44][C:45]([C:47]1[CH:52]([C:53]2[CH:54]=[CH:55][CH:56]=[CH:57][C:58]=2[Cl:59])[C:51]([C:60]([O:62][CH3:63])=[O:61])=[C:50]([CH3:64])[NH:49][C:48]=1[CH2:65][O:66][CH2:67][CH2:68][NH2:69])=[O:46].[C:70](=[O:73])([OH:72])[O-:71].[K+]>CN(C)C=O>[CH3:63][O:62][C:60]([C:51]1[CH:52]([C:53]2[CH:54]=[CH:55][CH:56]=[CH:57][C:58]=2[Cl:59])[C:47]([C:45]([O:44][CH2:43][CH3:42])=[O:46])=[C:48]([CH2:65][O:66][CH2:67][CH2:68][NH:69][CH2:1][C:2]2[O:73][C:70](=[O:72])[O:71][C:4]=2[CH2:5][O:16][C:15](=[O:17])[CH2:14][CH:13]([OH:18])[CH2:12][CH:11]([OH:19])[CH2:10][CH2:9][N:8]2[C:4]([CH:2]([CH3:1])[CH3:3])=[C:5]([C:33](=[O:34])[NH:35][C:36]3[CH:41]=[CH:40][CH:39]=[CH:38][CH:37]=3)[C:6]([C:27]3[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=3)=[C:7]2[C:20]2[CH:25]=[CH:24][C:23]([F:26])=[CH:22][CH:21]=2)[NH:49][C:50]=1[CH3:64])=[O:61]

Participants

5

Reactant 3

HCID 2162AmlodipineHCID 60823AtorvastatinHCID 516893Potassium Bicarbonate

Product 1

HCID 85048726HCID 85048726, compound

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
0 °C

Procedure

A solution of 4,5-bis(bromomethyl)-1,3-dioxol-2-one (10 g, 36.8 mmol) in ethyl acetate (10 ml) is added dropwise to a mixture of atorvastatin (7.45 g, 12.9 mmol), potassium bicarbonate (3 g) and sodium iodide (0.05 g) in ethyl acetate (60 ml) and N,N-dimethylformamide (20 ml) at 5° C. and the mixture is stirred at room temperature for 8 h. Cold water (30 ml) is added with stirring and the organic phase is separated, washed with 5% aqueous sodium chloride and dried over anhydrous sodium sulfate. The solvent is removed under reduced pressure and the residue is purified by column chromatography on silica gel to yield the 5-bromomethyl-2-oxo-1,3-dioxol-4-yl)methyl ester of atorvastatin. A mixture of the 5-bromomethyl-2-oxo-1,3-dioxol-4-yl)methyl ester of atorvastatin (7.7 g, 10 mmol), amlodipine (5.25 g, 10 mmol) and potassium bicarbonate (1 g, 10 mmol) in N,N-dimethylformamide (50 ml) is stirred at 0° C. for 8 h. The solvent is removed in vacuo and the residue is dissolved in chloroform. The chloroform solution is washed with water, dried over anhydrous sodium sulfate and concentrated under reduced pressure to yield the title compound of Example One.

Workup

  1. customThe solvent is removed in vacuo
  2. dissolutionthe residue is dissolved in chloroform
  3. washThe chloroform solution is washed with water
  4. dry with materialdried over anhydrous sodium sulfate
  5. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-6ff22b1f88624686a927268ad08f836b
Source dataset
uspto-grants-2002_11
Patent number
US06486182B1

Reaction notes

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