Diisopropylethylamine → N-[1-[[(4R)-5,6-dihydro-4H-imidazo[1,2-a][1]benzazepin-4-yl]carbamoyl]cyclopropyl]-4-ethoxy-benzamide

HRID 2068533ノート

反応式

HRID 2068533 の反応式
I.I.[CH:3]1[N:7]2[C:8]3[CH:17]=[CH:16][CH:15]=[CH:14][C:9]=3[CH2:10][CH2:11][C@@H:12]([NH2:13])[C:6]2=[N:5][CH:4]=1.[CH2:18]([O:20][C:21]1[CH:35]=[CH:34][C:24]([C:25]([NH:27][C:28]2([C:31](O)=[O:32])[CH2:30][CH2:29]2)=[O:26])=[CH:23][CH:22]=1)[CH3:19].O.ON1C2C=CC=CC=2N=N1.C(N(C(C)C)CC)(C)C.Cl.CN(C)CCCN=C=NCC>ClCCl>[CH:3]1[N:7]2[C:8]3[CH:17]=[CH:16][CH:15]=[CH:14][C:9]=3[CH2:10][CH2:11][C@@H:12]([NH:13][C:31]([C:28]3([NH:27][C:25](=[O:26])[C:24]4[CH:34]=[CH:35][C:21]([O:20][CH2:18][CH3:19])=[CH:22][CH:23]=4)[CH2:30][CH2:29]3)=[O:32])[C:6]2=[N:5][CH:4]=1

参加物

7

反応物 5

HCID 81531DiisopropylethylamineHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 27960291-Hydroxybenzotriazole hydrateHCID 583041121-[(4-Ethoxybenzoyl)amino]cyclopropanecarboxylic acidHCID 67234232(4R)-5,6-Dihydro-4H-imidazo[1,2-a][1]benzazepin-4-amine dihydroiodide

生成物 1

HCID 53242014N-[1-[[(4R)-5,6-dihydro-4H-imidazo[1,2-a][1]benzazepin-4-yl]carbamoyl]cyclopropyl]-4-ethoxy-benzamide収率 93%

試薬・触媒・溶媒 1

HCID 6344Dichloromethane溶媒

実験手順

Add (4R)-5,6-dihydro-4H-imidazo[1,2-a][1]benzazepin-4-amine dihydroiodide (650 g, 1.43 mol), 1-[(4-ethoxybenzoyl)amino]cyclopropanecarboxylic acid (427 g, 1.71 mol), and 1-hydroxybenzotriazole hydrate (262.5 g. 1.71 mol) to dichloromethane (3 L). Stir the mixture in an ice water bath and slowly add diisopropylethylamine (797 ml, 4.57 mol). Add 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (333.6 g, 1.71 mol) over 10 minutes. Remove the ice water bath and allow the mixture to stir for approximately 16 hours at ambient temperature. Wash the reaction mixture with water (3×4 L). Dry the organic phase over sodium sulfate. Filter and concentrate the mixture under reduced pressure to approximately 1 L volume. Dilute the residue with ethyl acetate (4 L). Remove 2 L of solvent under reduced pressure. Allow mixture to stand 1 hour at ambient temperature. Isolate the resulting precipitate by filtration and wash the cake with hexanes (2×2 L) to give the title compound (569.9 g, 93%) as a pale tan solid: MS (m/z): 431 (M+1). H1 NMR (399.81 MHz, DMSO): 8.91 (s, 1H), 7.95-7.93 (d, J=7.5 Hz, 1H), 7.87-7.83 (d, J=8.7 Hz, 2H), 7.49 (d, J=1.4 Hz, 1H), 7.44-7.43 (d, J=7.6 Hz, 1H), 7.38 (m, 2H), 7.34-7.29 (m, 1H), 7.00-6.96 (d, J=8.7 Hz, 2H), 6.95 (d, J=1.3 Hz, 1H), 4.65-4.60 (m, 1H), 4.08 (q, J=7.0 Hz, 2H), 2.70-2.65 (m, 1H), 2.59-2.56 (m, 1H), 2.33-2.28 (m, 1H), 2.04-2.00 (m, 1H), 1.34-1.31 (m, 4H), 1.27-1.25 (m, 1H), 1.03-0.98 (m, 1H), 0.96-0.90 (m, 1H).

後処理

  1. customRemove the ice water bath
  2. stirringto stir for approximately 16 hours at ambient temperature
  3. washWash the reaction mixture with water (3×4 L)
  4. dry with materialDry the organic phase over sodium sulfate
  5. filtrationFilter
  6. concentrationconcentrate the mixture under reduced pressure to approximately 1 L volume
  7. additionDilute the residue with ethyl acetate (4 L)
  8. customRemove 2 L of solvent under reduced pressure
  9. customIsolate the resulting precipitate
  10. filtrationby filtration
  11. washwash the cake with hexanes (2×2 L)

出典と根拠

ORDレコード
ord-4a70dee6a15541ceaa3c01aa90eed47b
出典データセット
uspto-grants-2012_10
特許番号
US08299061B2

反応ノート

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