Triethylamine → 2-Butyl-7-methoxycarbonyl-4-{4-[(2,5-dioxo-2,5-dihydro-1H-pyrrol-1-yl)methyl]cyclohexanecarboxamido}-1-(2-hydroxy-2-methylpropyl)-1H-imidazo[4,5-c]quinoline

HRID 574010

Reaktionsgleichung

Reaktionsgleichung von HRID 574010
[NH2:1][C:2]1[C:11]2[N:12]=[C:13]([CH2:20][CH2:21][CH2:22][CH3:23])[N:14]([CH2:15][C:16]([OH:19])([CH3:18])[CH3:17])[C:10]=2[C:9]2[CH:8]=[CH:7][C:6]([C:24]([O:26][CH3:27])=[O:25])=[CH:5][C:4]=2[N:3]=1.[O:28]=[C:29]1[CH:33]=[CH:32][C:31](=[O:34])[N:30]1[CH2:35][CH:36]1[CH2:41][CH2:40][CH:39]([C:42](ON2C(=O)CCC2=O)=[O:43])[CH2:38][CH2:37]1.CCN(CC)CC>CN(C=O)C>[CH2:20]([C:13]1[N:14]([CH2:15][C:16]([OH:19])([CH3:17])[CH3:18])[C:10]2[C:9]3[CH:8]=[CH:7][C:6]([C:24]([O:26][CH3:27])=[O:25])=[CH:5][C:4]=3[N:3]=[C:2]([NH:1][C:42]([CH:39]3[CH2:38][CH2:37][CH:36]([CH2:35][N:30]4[C:29](=[O:28])[CH:33]=[CH:32][C:31]4=[O:34])[CH2:41][CH2:40]3)=[O:43])[C:11]=2[N:12]=1)[CH2:21][CH2:22][CH3:23]

Komponenten

5

Edukt 3

HCID 8471TriethylamineHCID 125175Succinimidyl 4-(N-maleimidomethyl)cyclohexanecarboxylateHCID 712840524-Amino-2-butyl-1-(2-hydroxy-2-methylpropyl)-7-methoxycarbonyl-1H-imidazo[4,5-c]quinoline

Produkt 1

HCID 712922232-Butyl-7-methoxycarbonyl-4-{4-[(2,5-dioxo-2,5-dihydro-1H-pyrrol-1-yl)methyl]cyclohexanecarboxamido}-1-(2-hydroxy-2-methylpropyl)-1H-imidazo[4,5-c]quinolineAusbeute 68 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 6228DimethylformamideLösungsmittel

Reaktionsbedingungen

Temperatur
50 °C

Versuchsvorschrift

To a solution of 4-amino-2-butyl-1-(2-hydroxy-2-methylpropyl)-7-methoxycarbonyl-1H-imidazo[4,5-c]quinoline S7 (37 mg, 0.1 mmol, 1.0 equiv) and 2,5-dioxopyrrolidin-1-yl 4-[(2,5-dioxo-2,5-dihydro-1H-pyrrol-1-yl)methyl]cyclohexanecarboxylate (66 mg, 0.20 mmol, 2.0 equiv) in DMF (2.0 mL) at 25° C. was added NEt3 (40 μL, 0.30 mmol, 3.0 equiv) in one injection. The reaction was heated at 50° C. for 24 h. The solvent was then removed in vacuo and the solid was redissolved in 1:9 MeOH/EtOAc (50 mL), washed successively with saturated NaHCO3 solution (15 mL), H2O (15 mL) and saturated aqueous NaCl (15 mL) and the organic layer concentrated. TLC and MS analysis indicated existence of both the imidazoquinoline starting material and the desired product. Purification by flash column chromatography on silica gel (CH2Cl2-1/9 MeOH/CH2Cl2, gradient) afforded the title compound 550 (40 mg, 68%) as a white solid: 1H NMR (CD3OD, 600 Hz) δ1.04 (t, J=7.2 Hz, 3H), 1.11-1.18 (m, 2H), 1.26 (br s, 6H), 1.51-1.66 (m, 4H), 1.68-1.85 (m, 3H), 1.91 (pent, J=7.2 Hz, 2H), 3.13 (t, J=7.2 Hz, 2H), 3.40 (d, J=7.2 Hz, 2H), 6.83 (s, 2H), 7.98 (d, J=9.0 Hz, 1H), 8.41 (d, J=9.0 Hz, 1H), 8.66 (s, 1H); 13C NMR (CD3OD, 150 Hz) δ 12.9, 22.3, 27.2, 28.5, 28.7, 29.5, 29.6, 36.6, 43.1, 45.4, 51.4, 54.9, 71.1, 119.9, 121.4, 123.7, 126.5, 126.6, 126.6, 128.0, 128.8, 130.5, 133.9, 135.2, 142.5, 144.3, 158.2, 159.9, 160.0, 166.8, 171.4; MS (APCI+): calcd C32H40N5O6 [M+H]+ 590.3. found 590.3.

Aufarbeitung

  1. customThe solvent was then removed in vacuo
  2. dissolutionthe solid was redissolved in 1:9 MeOH/EtOAc (50 mL)
  3. washwashed successively with saturated NaHCO3 solution (15 mL), H2O (15 mL) and saturated aqueous NaCl (15 mL)
  4. concentrationthe organic layer concentrated
  5. customPurification by flash column chromatography on silica gel (CH2Cl2-1/9 MeOH/CH2Cl2, gradient)

Quellen und Nachweise

ORD-Eintrag
ord-ba0f90409722447185dc2e271573665b
Quelldatensatz
uspto-grants-2015_05
Patentnummer
US09034336B2

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