N,N-Dimethylsulfamide → 7H-indolo[2,1-a][2]benzazepine-10-carboxamide

HRID 1453353Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1453353
[CH:1]1[C:11]2[C:10]3=[CH:12][C:13]4[CH:14]=[CH:15][C:16]([C:19]([OH:21])=O)=[CH:17][C:18]=4[N:9]3[CH2:8][CH:7]=[CH:6][C:5]=2[CH:4]=[CH:3][CH:2]=1.C[N:23](C)S(N)(=O)=O.Cl.CN(C)CCCN=C=NCC>CN(C1C=CN=CC=1)C.CC(N(C)C)=O>[CH:1]1[C:11]2[C:10]3=[CH:12][C:13]4[CH:14]=[CH:15][C:16]([C:19]([NH2:23])=[O:21])=[CH:17][C:18]=4[N:9]3[CH2:8][CH:7]=[CH:6][C:5]=2[CH:4]=[CH:3][CH:2]=1

Komponenten

6

Edukt 3

HCID 134472N,N-DimethylsulfamideHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 666396797H-indolo[2,1-a][2]benzazepine-10-carboxylic acid

Produkt 1

HCID 666396907H-indolo[2,1-a][2]benzazepine-10-carboxamide

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 142844-(Dimethylamino)pyridineKatalysatorHCID 31374DimethylacetamideLösungsmittel

Reaktionsbedingungen

Temperatur
50 °C

Versuchsvorschrift

To a stirred solution of 7H-indolo[2,1-a][2]benzazepine-10-carboxylic acid, 13-cyclohexyl-6-[[4-(4-morpholinylcarbonyl)-1-piperazinyl]carbonyl] (70 mg, 0.12 mmol), N,N-dimethylsulfamide (75 mg, 0.60 mmol) and DMAP (75 mg, 0.61 mmol) in dimethylacetamide (1.5 mL) was added 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (92 mg, 0.48 mmol). The reaction solution was stirred at 50° C. overnight, concentrated, purified by preparative HPLC (MeOH/2O with NH4OAc buffer) and repurified by preparative HPLC (MeOH/2O with TFA buffer) to yield 7H-indolo[2,1-a][2]benzazepine-10-carboxamide, 13-cyclohexyl-N-[(dimethylamino)sulfonyl]-6-[[4-(4-morpholinylcarbonyl)-1-piperazinyl]carbonyl] (28 mg, 0.041 mol, 34%) as a yellow solid. 1H NMR (500 MHz, CDCl3) δ 9.09 (br s, 1H), 8.11 (s, 1H), 7.91 (d, J=8.5 Hz, 1H), 7.58 (br d, J=7.3 Hz, 1H), 7.54-7.45 (m, 3H), 7.41 (br d, J=7.3 Hz, 1H), 6.87 (s, 1H), 5.16 (br s, 1H), 4.37 (br s, 1H), 3.66 (dd, J=4.6, 4.6 Hz, 4H), 3.59-3.40 (m, 4H), 3.27(dd, J=4.6, 4.6 Hz, 4H), 3.19-3.07 (m, 4H), 3.06 (s, 6H), 2.89-2.80 (m, 1H), 2.13-1.17 (m, 10H). LCMS: m/e 674 (M−H)−, ret time 1.85 min, column A, 2 minute gradient.

Aufarbeitung

  1. concentrationconcentrated
  2. custompurified by preparative HPLC (MeOH/2O with NH4OAc buffer)
  3. customrepurified by preparative HPLC (MeOH/2O with TFA buffer)

Quellen und Nachweise

ORD-Eintrag
ord-9a8f42b022134326b3d3a098998f06ba
Quelldatensatz
uspto-grants-2009_01
Patentnummer
US07473688B2

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