Diisopropylethylamine → 1-{4-[(3,5-Dimethyl-pyridin-2-ylmethyl)-isoquinolin-1-ylmethyl-amino]-butyl}-3-(1H-imidazol-2-yl)-1-methyl-urea

HRID 251012

Reaktionsgleichung

Reaktionsgleichung von HRID 251012
[CH3:1][C:2]1[C:3]([CH2:9][N:10]([CH2:17][C:18]2[C:27]3[C:22](=[CH:23][CH:24]=[CH:25][CH:26]=3)[CH:21]=[CH:20][N:19]=2)[CH2:11][CH2:12]CCNC)=[N:4][CH:5]=[C:6]([CH3:8])[CH:7]=1.CCN(C(C)C)C(C)C.[NH:37]1[CH:41]=[CH:40][N:39]=[C:38]1[NH:42][C:43]([N:45]1[CH:49]=[CH:48]N=[CH:46]1)=[O:44]>CN(C=O)C>[CH3:1][C:2]1[C:3]([CH2:9][N:10]([CH2:17][C:18]2[C:27]3[C:22](=[CH:23][CH:24]=[CH:25][CH:26]=3)[CH:21]=[CH:20][N:19]=2)[CH2:11][CH2:12][CH2:48][CH2:49][N:45]([CH3:46])[C:43]([NH:42][C:38]2[NH:37][CH:41]=[CH:40][N:39]=2)=[O:44])=[N:4][CH:5]=[C:6]([CH3:8])[CH:7]=1

Komponenten

5

Edukt 3

HCID 81531DiisopropylethylamineHCID 11462607N-(3,5-Dimethyl-pyridin-2-ylmethyl)-N-isoquinolin-1-ylmethyl-N'-methyl-butane-1,4-diamineHCID 45120888N-(1H-Imidazol-2-yl)-1H-imidazole-1-carboxamide

Produkt 1

HCID 589969931-{4-[(3,5-Dimethyl-pyridin-2-ylmethyl)-isoquinolin-1-ylmethyl-amino]-butyl}-3-(1H-imidazol-2-yl)-1-methyl-ureaAusbeute 86 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 6228DimethylformamideLösungsmittel

Reaktionsbedingungen

Temperatur
70 °C

Versuchsvorschrift

To a warm (70° C.), stirred, solution of N-(3,5-Dimethyl-pyridin-2-ylmethyl)-N-isoquinolin-1-ylmethyl-N′-methyl-butane-1,4-diamine (0.204 g, 0.56 mmol) and DIPEA (0.59 mL, 3.39 mmol) in DMF (5 mL) was added freshly prepared imidazole-1-carboxylic acid (1H-imidazol-2-yl)-amide (2 equivs). After 1.5 hours, the mixture was cooled to room temperature and concentrated under reduced pressure. The residue was dissolved in CH2Cl2 (50 mL) and washed with water (5×10 mL). The organic phase was dried (Na2SO4) and concentrated. Purification of the crude material by column chromatography on silica gel (20:1:1 CH2Cl2-MeOH—NH4OH) provided 234 mg (86%) of COMPOUND 156 as a white solid. 1H NMR (CDCl3) δ 1.26-1.34 (m, 2H), 1.42-1.48 (m, 2H), 2.09 (s, 3H), 2.28 (s, 3H), 2.58 (t, 2H, J=7.5 Hz), 2.74 (s, 3H), 3.10 (t, 2H, J=7.5 Hz), 3.80 (s, 2H), 4.17 (s, 2H), 6.68 (s, 2H), 7.24-7.26 (m, 1H), 7.35-7.40 (m, 1H), 7.52-7.60 (m, 2H), 7.73 (d, 1H, J=8.1 Hz), 7.97 (d, 1H, J=8.7 Hz), 8.22 (s, 1H), 8.41 (d, 1H, J=5.7 Hz); 13C NMR (CDCl3) δ 18.33, 18.40, 23.93, 25.82, 34.90, 48.89, 54.57, 59.86, 59.96, 120.82, 126.71, 126.92, 127.20, 128.12, 130.13, 132.27, 133.15, 136.62, 139.08, 141.76, 145.16, 146.87, 154.33, 156.14, 159.39; ES-MS m/z 472 (M+1). Anal. Calcd. For C27H33N7O.0.5H2O: C, 67.48; H, 7.13; N, 20.40. Found: C, 67.57; H, 7.08; N, 20.52.

Aufarbeitung

  1. temperaturethe mixture was cooled to room temperature
  2. concentrationconcentrated under reduced pressure
  3. dissolutionThe residue was dissolved in CH2Cl2 (50 mL)
  4. washwashed with water (5×10 mL)
  5. dry with materialThe organic phase was dried (Na2SO4)
  6. concentrationconcentrated
  7. customPurification of the crude material by column chromatography on silica gel (20:1:1 CH2Cl2-MeOH—NH4OH)

Quellen und Nachweise

ORD-Eintrag
ord-5046f32a32c24187b62efb49c8bf1c77
Quelldatensatz
uspto-grants-2011_01
Patentnummer
US07863293B2

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