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

HRID 2068533노트

반응식

HRID 2068533 반응식
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

참가 물질

7

반응물 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

생성물 1

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

시약·촉매·용매 1

HCID 6344Dichloromethane용매

실험 절차

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).

후처리

  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)

출처 및 근거

ORD 기록
ord-4a70dee6a15541ceaa3c01aa90eed47b
출처 데이터셋
uspto-grants-2012_10
특허 번호
US08299061B2

반응 노트

불러오는 중…