Aldoxime → 2-[4-(3,5-dimethyl-4,5-dihydro-isoxazol-5-yl)phenyl]-N-{(1R)-1-[5-(2,2,2-trifluoroethoxy)pyridin-2-yl]ethyl}acetamide

HRID 474153Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 474153
[CH:1](=[N:3][OH:4])[CH3:2].ClN1C(=O)CCC1=O.[C:13]([C:16]1[CH:21]=[CH:20][C:19]([CH2:22][C:23]([NH:25][C@@H:26]([C:28]2[CH:33]=[CH:32][C:31]([O:34][CH2:35][C:36]([F:39])([F:38])[F:37])=[CH:30][N:29]=2)[CH3:27])=[O:24])=[CH:18][CH:17]=1)([CH3:15])=[CH2:14]>>[CH3:2][C:1]1[CH2:15][C:13]([C:16]2[CH:17]=[CH:18][C:19]([CH2:22][C:23]([NH:25][C@@H:26]([C:28]3[CH:33]=[CH:32][C:31]([O:34][CH2:35][C:36]([F:39])([F:37])[F:38])=[CH:30][N:29]=3)[CH3:27])=[O:24])=[CH:20][CH:21]=2)([CH3:14])[O:4][N:3]=1

Komponenten

4

Edukt 3

HCID 7863AldoximeHCID 31398ChlorosuccinimideHCID 247654022-(4-isopropenylphenyl)-N-{(1R)-1-[5-(2,2,2-trifluoroethoxy)pyridin-2-yl]ethyl}acetamide

Produkt 1

HCID 426100162-[4-(3,5-dimethyl-4,5-dihydro-isoxazol-5-yl)phenyl]-N-{(1R)-1-[5-(2,2,2-trifluoroethoxy)pyridin-2-yl]ethyl}acetamideAusbeute 23 %

Versuchsvorschrift

To a solution of acetaldoxime (14.1 mg, 0.238 mmol) was added N-chlorosuccinimide (31.8 mg, 0.238 mmol). The resulting mixture was stirred at room temperature for 3 h. 2-(4-Isopropenylphenyl)-N-{(1R)-1-[5-(2,2,2-trifluoroethoxy)pyridin-2-yl]ethyl}acetamide (90 mg, 0.24 mmol) was added, followed by the TEA (0.099 ml, 0.71 mmol), the resulting mixture was stirred at room temperature for 24 h. The reaction mixture was washed with saturated sodium bicarbonate solution and brine. Organics were extracted with CH2Cl2, dried over Na2SO4, filtered and concentrated in vacuo. Purification by reverse phase chromatography gave 2-[4-(3,5-dimethyl-4,5-dihydro-isoxazol-5-yl)phenyl]-N-{(1R)-1-[5-(2,2,2-trifluoroethoxy)pyridin-2-yl]ethyl}acetamide as a white solid (23.8 mg, 23%). 1H NMR (CDCl3, 400 MHz). δ 8.299 (dd, J=2.75, 5.31 Hz, 1H); 7.407 (t, J=2.93 Hz, 1H); 7.361 (dd, J=1.28 Hz, J=8.42 Hz, 4H); 7.243 (d, J=2.20 Hz, 1H); 7.222 (d, J=2.38 Hz, 1H); 5.122 (quintet, J=7.14 Hz, 1H); 4.436 (m, 2H); 3.550 (s, 2H); 3.063 (m, 2H); 1.965 (t, J=1.10 Hz, 3H); 1.684 (d, J=1.10 Hz, 2H); 1.466 (d, J=6.96 Hz, 3H); MS (ES): m/z 436.2 (M+H). FLIPR alpha1I IP=41 nM.

Aufarbeitung

  1. stirringthe resulting mixture was stirred at room temperature for 24 h
  2. washThe reaction mixture was washed with saturated sodium bicarbonate solution and brine
  3. extractionOrganics were extracted with CH2Cl2
  4. dry with materialdried over Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. customPurification by reverse phase chromatography

Quellen und Nachweise

ORD-Eintrag
ord-47e6031bc74c47aabff00e42e616db69
Quelldatensatz
uspto-grants-2014_01
Patentnummer
US08637513B2

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