Triethylamine → cyclopropanecarboxylic acid {7-chloro-2-[2-cyano-1-(3-ethoxy-4-methoxy-phenyl)-ethyl]-3-oxo-2,3-dihydro-1H-isoindol-4-yl}-amide

HRID 853977Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 853977
[NH2:1][CH:2]([C:6]1[CH:11]=[CH:10][C:9]([O:12][CH3:13])=[C:8]([O:14][CH2:15][CH3:16])[CH:7]=1)[CH2:3][C:4]#[N:5].CCN(CC)CC.C[O:25][C:26](=O)[C:27]1[C:32]([NH:33][C:34]([CH:36]2[CH2:38][CH2:37]2)=[O:35])=[CH:31][CH:30]=[C:29]([Cl:39])[C:28]=1[CH2:40]Br>CN(C=O)C>[Cl:39][C:29]1[CH:30]=[CH:31][C:32]([NH:33][C:34]([CH:36]2[CH2:37][CH2:38]2)=[O:35])=[C:27]2[C:28]=1[CH2:40][N:1]([CH:2]([C:6]1[CH:11]=[CH:10][C:9]([O:12][CH3:13])=[C:8]([O:14][CH2:15][CH3:16])[CH:7]=1)[CH2:3][C:4]#[N:5])[C:26]2=[O:25]

Komponenten

5

Edukt 3

HCID 8471TriethylamineHCID 221771543-Amino-3-(3-ethoxy-4-methoxyphenyl)propanenitrileHCID 669200082-Bromomethyl-3-chloro-6-(cyclopropanecarbonyl-amino)-benzoic acid methyl ester

Produkt 1

HCID 9981379cyclopropanecarboxylic acid {7-chloro-2-[2-cyano-1-(3-ethoxy-4-methoxy-phenyl)-ethyl]-3-oxo-2,3-dihydro-1H-isoindol-4-yl}-amideAusbeute 80 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 6228DimethylformamideLösungsmittel

Reaktionsbedingungen

Temperatur
90 °C

Versuchsvorschrift

To the DMF solution (20 ml) of 3-Amino-3-(3-ethoxy-4-methoxy-phenyl)-propionitrile (1.55 g, 7 mmol) was added Et3N (1.6 ml, 12 mmol) followed by 2-bromomethyl-3-chloro-6-(cyclopropanecarbonyl-amino)-benzoic acid methyl ester (2.42 g, 7 mmol). The mixture was heated at 90° C. for 12 hrs then cooled to room temperature. The mixture was extracted with EtOAc (50 ml) and water (50 ml). The organic layer was washed with water (50 ml) and brine (50 ml), dried over Na2SO4 and concentrated in vacuo. The resulted oil was purified by silica gel chromatography to give cyclopropanecarboxylic acid {7-chloro-2-[2-cyano-1-(3-ethoxy-4-methoxy-phenyl)-ethyl]-3-oxo-2,3-dihydro-1H-isoindol-4-yl}-amide as white solid (2.4 g, 80%): mp 200-202° C.; 1H NMR (CDCl3)δ 0.90-0.94 (m, 2H, c-CH2), 1.09-1.14 (m, 2H, c-CH2), 1.45 (t, J=7.0 Hz, 3H, CH3), 1.64-1.70(m, 1H, c-CH), 3.12-3.32(m, 2H; CH2CN), 3.89(s, 3H), 3.99-4.12 (m, 3H, OCH2CH3+CHHN), 4.37 (d, J=18 Hz, 1H. CHHN), 5.62-5.68 (m, 1H, NCH), 6.87-6.98 (m, 3H, Ar), 7.40 (d, J=9 Hz, 1H, Ar), 8.47 (t, J=9 Hz, 1H, Ar), 10.34 (s, 1H, NH); 3C NMR (CDCl3) δ 8.5, 14.7, 16.2, 21.2, 46.4, 51.8, 56.0, 64.7, 111.7, 112.2, 116.9, 118.4, 119.1, 119.8, 121.9, 127.9, 133.3, 136.9, 138.9, 149.9, 150.0, 169.0, 172.7; Anal Calcd for C24H24ClN3O4: C, 63.50; H, 5.33; N, 9.26. Found: C, 63.43; H, 5.31; N, 9.01

Aufarbeitung

  1. temperaturethen cooled to room temperature
  2. extractionThe mixture was extracted with EtOAc (50 ml) and water (50 ml)
  3. washThe organic layer was washed with water (50 ml) and brine (50 ml)
  4. dry with materialdried over Na2SO4
  5. concentrationconcentrated in vacuo
  6. customThe resulted oil was purified by silica gel chromatography

Quellen und Nachweise

ORD-Eintrag
ord-d1fc3d78f7d8433db8fcad028bea3024
Quelldatensatz
uspto-grants-2007_08
Patentnummer
US07256210B2

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