Amlodipine → HCID 86758618, compound

HRID 1019020Notes

Reaction equation

HRID 1019020 reaction equation
Cl[C:2]([O:4][CH2:5]Cl)=[O:3].[CH3:7][CH2:8][O:9][C:10]([C:12]1[CH:17]([C:18]2[CH:19]=[CH:20][CH:21]=[CH:22][C:23]=2[Cl:24])[C:16]([C:25]([O:27][CH3:28])=[O:26])=[C:15]([CH3:29])[NH:14][C:13]=1[CH2:30][O:31][CH2:32][CH2:33][NH2:34])=[O:11].[Ca].[CH3:36][CH:37]([C:39]1[N:43]([CH2:44][CH2:45][C@@H:46]([OH:54])[CH2:47][C@@H:48]([OH:53])[CH2:49][C:50]([OH:52])=[O:51])[C:42]([C:55]2[CH:56]=[CH:57][C:58]([F:61])=[CH:59][CH:60]=2)=[C:41]([C:62]2[CH:63]=[CH:64][CH:65]=[CH:66][CH:67]=2)[C:40]=1[C:68]([NH:70][C:71]1[CH:72]=[CH:73][CH:74]=[CH:75][CH:76]=1)=[O:69])[CH3:38]>C(Cl)(Cl)Cl.N1C=CC=CC=1>[CH3:28][O:27][C:25]([C:16]1[CH:17]([C:18]2[CH:19]=[CH:20][CH:21]=[CH:22][C:23]=2[Cl:24])[C:12]([C:10]([O:9][CH2:8][CH3:7])=[O:11])=[C:13]([CH2:30][O:31][CH2:32][CH2:33][NH:34][C:2]([O:4][CH2:5][O:52][C:50](=[O:51])[CH2:49][CH:48]([OH:53])[CH2:47][CH:46]([OH:54])[CH2:45][CH2:44][N:43]2[C:39]([CH:37]([CH3:36])[CH3:38])=[C:40]([C:68](=[O:69])[NH:70][C:71]3[CH:72]=[CH:73][CH:74]=[CH:75][CH:76]=3)[C:41]([C:62]3[CH:63]=[CH:64][CH:65]=[CH:66][CH:67]=3)=[C:42]2[C:55]2[CH:56]=[CH:57][C:58]([F:61])=[CH:59][CH:60]=2)=[O:3])[NH:14][C:15]=1[CH3:29])=[O:26]

Participants

7

Reactant 4

HCID 2162AmlodipineHCID 60823AtorvastatinHCID 62754Chloromethyl chloroformateHCID 5460341Calcium

Product 1

HCID 86758618HCID 86758618, compound

Reagents, catalysts & solvents 2

HCID 1049PyridineSolventHCID 6212ChloroformSolvent

Procedure

Chloromethyl chloroformate (2.85 g, 22 mmol) is added to amlodipine (10.5 g, 20 mmol) and pyridine (1.6 g) in 300 ml chloroform cooled in an ice bath. The reaction mixture is stirred at room temperature for 16 h, washed with water, dried (anhydrous sodium sulfate) and concentrated under reduced pressure. The residue is dissolved in dimethylformamide (50 ml) containing the calcium salt of atorvastatin (10.75 g, 0.018 mol) and the reaction mixture is heated at 80° C. for 20 h. The dimethylformamide is removed in vacuo and the residue is triturated with chloroform-hexane to yield the title compound the title compound of Example Two.

Workup

  1. temperaturecooled in an ice bath
  2. washwashed with water
  3. dry with materialdried (anhydrous sodium sulfate)
  4. concentrationconcentrated under reduced pressure
  5. dissolutionThe residue is dissolved in dimethylformamide (50 ml)
  6. temperaturethe reaction mixture is heated at 80° C. for 20 h
  7. customThe dimethylformamide is removed in vacuo
  8. customthe residue is triturated with chloroform-hexane

Sources & evidence

ORD record
ord-515c249ab1b544f6b9c2313c5e5ab908
Source dataset
uspto-grants-2002_11
Patent number
US06486182B1

Reaction notes

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