Diisopropylethylamine → N-[2-(2,6-dioxo-piperidin-3-yl)-1,3-dioxo-2,3-dihydro-1H-isoindol-4-ylmethyl]-4-fluoro-3-trifluoromethyl-benzamide

HRID 448497Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 448497
Cl.[NH2:2][CH2:3][C:4]1[CH:12]=[CH:11][CH:10]=[C:9]2[C:5]=1[C:6](=[O:22])[N:7]([CH:14]1[CH2:19][CH2:18][C:17](=[O:20])[NH:16][C:15]1=[O:21])[C:8]2=[O:13].[F:23][C:24]1[CH:32]=[CH:31][C:27]([C:28](Cl)=[O:29])=[CH:26][C:25]=1[C:33]([F:36])([F:35])[F:34].C(N(C(C)C)CC)(C)C>C(Cl)Cl>[O:21]=[C:15]1[CH:14]([N:7]2[C:6](=[O:22])[C:5]3[C:9](=[CH:10][CH:11]=[CH:12][C:4]=3[CH2:3][NH:2][C:28](=[O:29])[C:27]3[CH:31]=[CH:32][C:24]([F:23])=[C:25]([C:33]([F:36])([F:34])[F:35])[CH:26]=3)[C:8]2=[O:13])[CH2:19][CH2:18][C:17](=[O:20])[NH:16]1

Komponenten

5

Edukt 3

HCID 81531DiisopropylethylamineHCID 1442534-Fluoro-3-(trifluoromethyl)benzoyl ChlorideHCID 219885254-(aminomethyl)-2-(2,6-dioxopiperidin-3-yl)-2,3-dihydro-1H-isoindole-1,3-dione hydrochloride

Produkt 1

HCID 67229011N-[2-(2,6-dioxo-piperidin-3-yl)-1,3-dioxo-2,3-dihydro-1H-isoindol-4-ylmethyl]-4-fluoro-3-trifluoromethyl-benzamideAusbeute 79 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 6344DichloromethaneLösungsmittel

Versuchsvorschrift

To a stirred suspension of 4-aminomethyl-2-(2,6-dioxo-piperidin-3-yl)-isoindole-1,3-dione hydrochloride (0.7 g, 2.2 mmol) and 4-fluoro-3-trifluoromethyl-benzoyl chloride (0.6 g, 2.8 mmol) in dry methylene chloride (60 mL), was added diisopropylethylamine (0.7 g, 5.4 mmol). After stirring at room temperature overnight, the reaction mixture was quenched with methanol (1 mL). The resulting suspension was filtered, and the solid was washed with methyene chloride to afford N-[2-(2,6-dioxo-piperidin-3-yl)-1,3-dioxo-2,3-dihydro-1H-isoindol-4-ylmethyl]-4-fluoro-3-trifluoromethyl-benzamide (0.8 g, 79%) as a white solid: mp 171-173° C.; HPLC: Waters Symmetry C-18, 3.9×150 mm, 5 micro, 1 mL/min, 240 nm, 40/60 (CH3CN/H2O): tR=7.5 min. (99%); 1H NMR (DMSO-d6) δ 2.06-2.12 (m, 1H), 2.54-2.65 (m, 2H), 2.85-2.98 (m, 1H), 4.97 (d, J=5.7 Hz, 2H), 5.15-5.21 (dd, J=5.4 and 12.5 Hz, 1H), 7.68 (t, J=8.9 Hz, 1H), 7.76-7.84 (m, 3H), 8.28-8.35 (m, 2H), 9.43 (t, J=5.7 Hz, 1H), 11.15 (s, 1H); 13C NMR (DMSO-d6) δ 21.91, 30.86, 38.43, 48.82, 116.20 (116.37, 116.64, 116.80), 117.35 (117.63), 120.50 (124.10), 121.92, 126.51 (126.56), 127.14, 130.65 (130.70), 131.48, 133.22, 134.58, 134.71 (134.77), 138.70, 158.78 (162.21), 164.19, 166.87, 167.44, 169.75, 172.68; Anal. Calcd. for C22H15N3O5F4+0.2H2O: C, 54.94; H, 3.23; N, 8.74; F, 15.80. Found: C, 54.68; H, 3.17; N, 8.63; F, 15.72.

Aufarbeitung

  1. customthe reaction mixture was quenched with methanol (1 mL)
  2. filtrationThe resulting suspension was filtered
  3. washthe solid was washed with methyene chloride

Quellen und Nachweise

ORD-Eintrag
ord-0a96e7434fec48308601c3accc2a41e0
Quelldatensatz
uspto-grants-2013_07
Patentnummer
US08481568B2

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