Amlodipine → 4-(2-Chlorophenyl)-3-ethoxycarbonyl-5-methoxycarbonyl-6-methyl-2-[2-(3-pyridylcarbonylamino)ethoxymethyl]-1,4-dihydropyridine

HRID 280569

Reaktionsgleichung

Reaktionsgleichung von HRID 280569
Cl.CN(C)[CH2:4][CH2:5][CH2:6][N:7]=[C:8]=NCC.[NH2:13][CH2:14][CH2:15][O:16][CH2:17][C:18]1[NH:19][C:20]([CH3:40])=[C:21]([C:36]([O:38][CH3:39])=[O:37])[CH:22]([C:29]2[CH:34]=[CH:33][CH:32]=[CH:31][C:30]=2[Cl:35])[C:23]=1[C:24]([O:26][CH2:27][CH3:28])=[O:25].O.ON1C2C=CC=CC=2N=N1.CN1CC[O:56][CH2:55][CH2:54]1>ClCCl>[Cl:35][C:30]1[CH:31]=[CH:32][CH:33]=[CH:34][C:29]=1[CH:22]1[C:21]([C:36]([O:38][CH3:39])=[O:37])=[C:20]([CH3:40])[NH:19][C:18]([CH2:17][O:16][CH2:15][CH2:14][NH:13][C:55]([C:54]2[CH:8]=[N:7][CH:6]=[CH:5][CH:4]=2)=[O:56])=[C:23]1[C:24]([O:26][CH2:27][CH3:28])=[O:25]

Komponenten

6

Edukt 4

HCID 2162AmlodipineHCID 79724-MethylmorpholineHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 27960291-Hydroxybenzotriazole hydrate

Produkt 1

HCID 145286914-(2-Chlorophenyl)-3-ethoxycarbonyl-5-methoxycarbonyl-6-methyl-2-[2-(3-pyridylcarbonylamino)ethoxymethyl]-1,4-dihydropyridineAusbeute 56,3 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 6344DichloromethaneLösungsmittel2×

Versuchsvorschrift

1-(3-Dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (0.42 g) was added to an ice-cooled solution of 2-(2-aminoethoxymethyl)-4-(2-chlorophenyl)-3-ethoxycarbonyl-5-methoxycarbonyl-6-methyl-1,4-dihydropyridine (0.41 g), nicetinic acid (0.14 g) and 1-hydroxybenzotriazole hydrate (0.17 g) in dichloromethane (40 ml). The mixture was stirred with ice-cooling for 15 minutes, treated with N-methylmorpholine (0.61 g) and stirred at room temperature for 16 hours. The solution was then diluted with dichloromethane, washed successively with water, 2N hydrochloric acid, water, 10% aqueous sodium carbonate solution, and water, dried (Na2SO4) and evaporated. The residue was chromatographed on silica (t.l.c. grade, Merck Kieselgel 60H (Trade Mark) 8 g) eluting with dichloromethane plus 0-5% methanol. Appropriate fractions were combined and evaporated. The residue was triturated with diethyl ether and the resulting solid collected, washed with diethyl ether and dried to give the title compound (0.29 g), m.p. 81°-84° C. Found: C. 61.01; H, 5.48; N, 8.23. C26H28ClN3O6 requires C, 60.76; H, 5.49; N, 8.18%.

Aufarbeitung

  1. temperaturecooling for 15 minutes
  2. stirringstirred at room temperature for 16 hours
  3. washwashed successively with water, 2N hydrochloric acid, water, 10% aqueous sodium carbonate solution, and water
  4. dry with materialdried (Na2SO4)
  5. customevaporated
  6. customThe residue was chromatographed on silica (t.l.c. grade, Merck Kieselgel 60H (Trade Mark) 8 g)
  7. washeluting with dichloromethane plus 0-5% methanol
  8. customevaporated
  9. customThe residue was triturated with diethyl ether
  10. customthe resulting solid collected
  11. washwashed with diethyl ether
  12. customdried

Quellen und Nachweise

ORD-Eintrag
ord-c906b866603b414bb4eb3f323d50d52a
Quelldatensatz
uspto-grants-1986_05
Patentnummer
US04590195

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