Triethylamine → N-[2-(3-methyl-2,6-dioxo-piperidin-3-yl)-1-oxo-2,3-dihydro-1H-isoindol-5-ylmethyl]-4-trifluoromethoxy-benzamide

HRID 63420

Reaktionsgleichung

Reaktionsgleichung von HRID 63420
Cl.[NH2:2][CH2:3][C:4]1[CH:5]=[C:6]2[C:10](=[CH:11][CH:12]=1)[C:9](=[O:13])[N:8]([CH:14]1[CH2:19][CH2:18][C:17](=[O:20])[NH:16][C:15]1=[O:21])[CH2:7]2.[F:22][C:23]([F:35])([F:34])[O:24][C:25]1[CH:33]=[CH:32][C:28]([C:29](Cl)=[O:30])=[CH:27][CH:26]=1.[CH2:36](N(CC)CC)C>CN(C)C=O.O>[CH3:36][C:14]1([N:8]2[CH2:7][C:6]3[C:10](=[CH:11][CH:12]=[C:4]([CH2:3][NH:2][C:29](=[O:30])[C:28]4[CH:32]=[CH:33][C:25]([O:24][C:23]([F:35])([F:34])[F:22])=[CH:26][CH:27]=4)[CH:5]=3)[C:9]2=[O:13])[CH2:19][CH2:18][C:17](=[O:20])[NH:16][C:15]1=[O:21]

Komponenten

6

Edukt 3

HCID 8471TriethylamineHCID 1421104-(Trifluoromethoxy)benzoyl ChlorideHCID 665895253-(5-(aminomethyl)-1-oxo-2,3-dihydro-1H-isoindol-2-yl)piperidine-2,6-dione hydrochloride

Produkt 1

HCID 44476534N-[2-(3-methyl-2,6-dioxo-piperidin-3-yl)-1-oxo-2,3-dihydro-1H-isoindol-5-ylmethyl]-4-trifluoromethoxy-benzamideAusbeute 71,9 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 962WaterLösungsmittelHCID 6228DimethylformamideLösungsmittel

Versuchsvorschrift

To a stirred mixture of 3-(5-aminomethyl-1-oxo-1,3-dihydro-isoindol-2-yl)-piperidine-2,6-dione hydrochloride (0.4 g, 1.20 mmol) and 4-(trifluoromethoxy)benzoyl chloride (0.27 g, 1.20 mmol) in N,N-dimethylformamide (15 mL), was added triethylamine (0.34 mL, 2.40 mmol) at room temperature under nitrogen. After 2 h, the mixture was diluted with water (60 mL) and stirred for 1 h. The product was isolated by filtration, washed with water (50 mL) and dried in vacuo providing N-[2-(3-methyl-2,6-dioxo-piperidin-3-yl)-1-oxo-2,3-dihydro-1H-isoindol-5-ylmethyl]-4-trifluoromethoxy-benzamide as an off-white solid (0.41 g, 71% yield): HPLC: Waters Symmetry C18, 5 μm, 3.9×150 mm, 1 mL/min, 240 nm, 40/60 CH3CN/0.1% H3PO4, 4.81 min (95.39%); mp: 224-226° C.; 1H NMR (DMSO-d6) δ 1.66 (s, 3H), 1.82-1.94 (m, 1H), 2.52-2.82 (m, 3H), 4.48-4.69 (m, 4H), 7.38-7.56 (m, 4H), 7.61 (d, J=7.9 Hz, 1H), 8.04 (d, J=8.7 Hz, 2H), 9.28 (t, J=5.5 Hz, 1H), 10.86 (s, 1H); 13C NMR (DMSO-d6) δ 20.74, 27.81, 29.01, 42.78, 47.64, 57.12, 119.9 (q, J=256 Hz), 120.68, 121.82, 122.58, 127.04, 129.60, 131.02, 133.36, 142.41, 143.57, 150.34, 165.06, 167.00, 172.44, 173.55; LCMS: MH=476; Anal Calcd for C23H20F3N3O5+0.7H2O: C, 56.61; H, 4.42; N, 8.61. Found: C, 56.60; H, 4.11; N, 8.61.

Aufarbeitung

  1. customThe product was isolated by filtration
  2. washwashed with water (50 mL)
  3. customdried in vacuo

Quellen und Nachweise

ORD-Eintrag
ord-db0f8a3e2bf1473786bebccd55203cc7
Quelldatensatz
uspto-grants-2016_09
Patentnummer
US09447070B2

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