1-Hydroxybenzotriazole → N-(2-(4-(4-fluorophenyl)thiazol-2-yl)propyl)-3-(5-(trifluoromethyl)-1,2,4-oxadiazol-3-yl)benzamide

HRID 1397439Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1397439
[F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[N:9]=[C:10]([CH:13]([CH3:16])[CH2:14][NH2:15])[S:11][CH:12]=2)=[CH:4][CH:3]=1.[F:17][C:18]([F:34])([F:33])[C:19]1[O:23][N:22]=[C:21]([C:24]2[CH:25]=[C:26]([CH:30]=[CH:31][CH:32]=2)[C:27](O)=[O:28])[N:20]=1.Cl.CN(C)CCCN=C=NCC.ON1C2C=CC=CC=2N=N1.C(N(C(C)C)CC)(C)C>ClCCl>[F:1][C:2]1[CH:3]=[CH:4][C:5]([C:8]2[N:9]=[C:10]([CH:13]([CH3:16])[CH2:14][NH:15][C:27](=[O:28])[C:26]3[CH:30]=[CH:31][CH:32]=[C:24]([C:21]4[N:20]=[C:19]([C:18]([F:34])([F:33])[F:17])[O:23][N:22]=4)[CH:25]=3)[S:11][CH:12]=2)=[CH:6][CH:7]=1

Komponenten

7

Edukt 5

HCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 242620152-(4-(4-Fluorophenyl)thiazol-2-yl)propan-1-amineHCID 251808543-(5-(Trifluoromethyl)-1,2,4-oxadiazol-3-yl)benzoic acid

Produkt 1

HCID 69950153N-(2-(4-(4-fluorophenyl)thiazol-2-yl)propyl)-3-(5-(trifluoromethyl)-1,2,4-oxadiazol-3-yl)benzamideAusbeute 36 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 6344DichloromethaneLösungsmittel2×

Versuchsvorschrift

2-(4-(4-Fluorophenyl)thiazol-2-yl)propan-1-amine (50 mg, 0.21 mmol), 3-(5-(trifluoromethyl)-1,2,4-oxadiazol-3-yl)benzoic acid (54.62 mg, 0.21 mmol), N-(3-dimethylaminopropyl)-N′-ethylcarbodiimide hydrochloride (EDC) (81.12 mg, 0.42 mmol), and 1-hydroxybenzotriazole (HOBt) (45.74 mg, 0.39 mmol) were dissolved in dichloromethane (3 mL) at room temperature. Diisopropylethylamine (DIEA) (0.147 mL, 0.85 mmol) was then introduced at room temperature and the reaction mixture was stirred at room temperature overnight. The reaction mixture was diluted with dichloromethane (100 mL) and washed with water (1×20 mL) and brine (1×20 mL). The organic layer was then dried over anhydrous sodium sulfate and concentrated under reduced pressure to give the crude product, which was purified on a Teledyne ISCO automated column chromatography system (0-30% EtOAc/Hexanes) to give N-(2-(4-(4-fluorophenyl)thiazol-2-yl)propyl)-3-(5-(trifluoromethyl)-1,2,4-oxadiazol-3-yl)benzamide (36 mg, 36% yield). 1H NMR (CDCl3) δ 8.50 (1h, s), 8.23 (1H, d, J=8 Hz), 8.03 (1H, 1H, d, J=8 Hz), 7.85-7.81 (3H, m), 7.58 (1H, t), 7.35 (1H, s), 7.03 (2H, m), 4.05 (1H, m), 3.65 (1H, m), 1.54 (3H, d, J=8 Hz). MS (ESI) m/z: Calculated for C22H16F4N4O2S: 476.09. found: 477.1 (M+H)+.

Aufarbeitung

  1. washwashed with water (1×20 mL) and brine (1×20 mL)
  2. dry with materialThe organic layer was then dried over anhydrous sodium sulfate
  3. concentrationconcentrated under reduced pressure
  4. customto give the crude product, which
  5. customwas purified on a Teledyne ISCO automated column chromatography system (0-30% EtOAc/Hexanes)

Quellen und Nachweise

ORD-Eintrag
ord-36fb0540217f4a11a9c3a2149068cb42
Quelldatensatz
uspto-grants-2014_12
Patentnummer
US08901156B2

Notizen zur Reaktion

Wird geladen…