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

HRID 280569
ノート
印刷プレビュー

反応式

HRID 280569 の反応式
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]
参加物実験手順後処理出典と根拠反応ノート

参加物

6

反応物 4

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

生成物 1

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

試薬・触媒・溶媒 1

HCID 6344Dichloromethane溶媒2 回

実験手順

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%.

後処理

  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

出典と根拠

ORDレコード
ord-c906b866603b414bb4eb3f323d50d52a
出典データセット
uspto-grants-1986_05
DOI
10.6084/m9.figshare.5104873.v1
特許番号
US04590195

反応ノート

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