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

HRID 280569

반응식

HRID 280569 반응식
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]

참가 물질

6

반응물 4

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

생성물 1

HCID 145286914-(2-Chlorophenyl)-3-ethoxycarbonyl-5-methoxycarbonyl-6-methyl-2-[2-(3-pyridylcarbonylamino)ethoxymethyl]-1,4-dihydropyridine수율 56.3%

시약·촉매·용매 1

HCID 6344Dichloromethane용매2회

실험 절차

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%.

후처리

  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

출처 및 근거

ORD 기록
ord-c906b866603b414bb4eb3f323d50d52a
출처 데이터셋
uspto-grants-1986_05
특허 번호
US04590195

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