1-Hydroxybenzotriazole → 13-cyclohexyl-N-[2-(dimethylamino)-2-oxoethyl]-6-[[4-(4-morpholinyl)-1-piperidinyl]carbonyl]-7H-indolo[2,1-a][2]benzazepine-10-carboxamide

HRID 1453398

Reaktionsgleichung

Reaktionsgleichung von HRID 1453398
[CH:1]1([C:7]2[C:8]3[CH:9]=[CH:10][C:11]([C:39]([NH2:41])=[O:40])=[CH:12][C:13]=3[N:14]3[CH2:20][C:19]([C:21]([N:23]4[CH2:28][CH2:27][CH:26]([N:29]5[CH2:34][CH2:33][O:32][CH2:31][CH2:30]5)[CH2:25][CH2:24]4)=[O:22])=[CH:18][C:17]4[CH:35]=[CH:36][CH:37]=[CH:38][C:16]=4[C:15]=23)[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1.C1(C2C3C=CC(C(O)=O)=CC=3N3C[C:60]([C:62]([N:64]4[CH2:69]CC(N5CCOCC5)C[CH2:65]4)=[O:63])=CC4C=CC=CC=4C=23)CCCCC1.C(N(CC)C(C)C)(C)C.Cl.Cl.NCCC1NC2C=CC=CC=2N=1.Cl.CN(C)CCCN=C=NCC.ON1C2C=CC=CC=2N=N1>C(Cl)Cl>[CH:1]1([C:7]2[C:8]3[CH:9]=[CH:10][C:11]([C:39]([NH:41][CH2:60][C:62]([N:64]([CH3:69])[CH3:65])=[O:63])=[O:40])=[CH:12][C:13]=3[N:14]3[CH2:20][C:19]([C:21]([N:23]4[CH2:28][CH2:27][CH:26]([N:29]5[CH2:34][CH2:33][O:32][CH2:31][CH2:30]5)[CH2:25][CH2:24]4)=[O:22])=[CH:18][C:17]4[CH:35]=[CH:36][CH:37]=[CH:38][C:16]=4[C:15]=23)[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6]1

Komponenten

8

Edukt 6

HCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 27880712-(2-Aminoethyl)benzimidazole dihydrochlorideHCID 5752668313-cyclohexyl-6-[[4-(4-morpholinyl)-1-piperidinyl]carbonyl]-7H-indolo[2,1-a][2]benzazepine-10-carboxylic acidHCID 86611779HCID 86611779, Verbindung

Produkt 1

HCID 5752671313-cyclohexyl-N-[2-(dimethylamino)-2-oxoethyl]-6-[[4-(4-morpholinyl)-1-piperidinyl]carbonyl]-7H-indolo[2,1-a][2]benzazepine-10-carboxamideAusbeute 34 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 6344DichloromethaneLösungsmittel

Versuchsvorschrift

N-[2-(]H-benzimidazol-2-yl)ethyl]-13-cyclohexyl-6-[[4-(4-morpholinyl)-1-piperidinyl]carbonyl]-7H-indolo[2,1-a][2]benzazepine-10-carboxamide. A solution of 13-cyclohexyl-6-[[4-(4-morpholinyl)-1-piperidinyl]carbonyl]-7H-indolo[2,1-a][2]benzazepine-10-carboxylic acid (47 mg, 0.085 mmol), N,N-diisopropylethylamine (60 μL, 0.34 mmol), 2-(2-aminoethyl)benzimidazole dihydrochloride (23 mg, 0.1 mmol), N-(3-dimethylaminopropyl)-N′-ethylcarbodiimide hydrochloride (23 mg, 0.12 mmol), and 1-hydroxybenzotriazole (16 mg, 0.12 mmol) in CH2Cl2 (3.1 mL) was stirred at r.t. overnight, then introduced directly to silica gel. Elution (gradient: 0%→5% MeOH in CH2C12) gave the title compound as a yellow powder (20 mg, 34% yield). LC/MS (ESI) retention time: 1.57 min, m/z 697 (MH+); 1H NMR (400 MHz, CDCl3) δ 1.09-1.21 (m, 1 H) 1.22-1.37 (m, 3 H) 1.38-1.48 (m, 1 H) 1.58-1.68 (m, 1 H) 1.69-1.76 (m, 2 H) 1.87 (t, 1 H) 1.97 (t, 2 H) 2.27 (t, J=10.95 Hz, 1 H) 2.39 (s, 3 H) 2.61-2.72 (m, 1 H) 2.72-2.82 (m, 1 H) 3.26 (t, J=6.04 Hz, 2 H) 3.61-3.70 (m, 4 H) 3.98 (s, 2 H) 4.18 (s, 1 H) 4.86 (s, 1 H) 6.80 (s, 1 H) 7.13 (dd, J=6.04, 3.27 Hz, 2 H) 7.33-7.38 (m, 2 H) 7.40-7.46 (m, 2 H) 7.46-7.53 (m, 3 H) 7.73 (d, J=8.56 Hz, 1 H) 7.77-7.85 (m, 1 H) 8.04 (s, 1 H).

Aufarbeitung

  1. additionintroduced directly to silica gel
  2. washElution (gradient: 0%→5% MeOH in CH2C12)

Quellen und Nachweise

ORD-Eintrag
ord-b0e171c9a7f848478da885d17068b9a8
Quelldatensatz
uspto-grants-2009_01
Patentnummer
US07473688B2

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