4-Methylmorpholine → N-((4-(4-phenylthiazol-2-yl)tetrahydro-2H-pyran-4-yl)methyl)-5-(5-(trifluoromethyl)-1,2,4-oxadiazol-3-yl)nicotinamide

HRID 1397212Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1397212
[F:1][C:2]([F:18])([F:17])[C:3]1[O:7][N:6]=[C:5]([C:8]2[CH:9]=[N:10][CH:11]=[C:12]([CH:16]=2)[C:13]([OH:15])=O)[N:4]=1.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.[C:43]1([C:49]2[N:50]=[C:51]([C:54]3([CH2:60][NH2:61])[CH2:59][CH2:58][O:57][CH2:56][CH2:55]3)[S:52][CH:53]=2)[CH:48]=[CH:47][CH:46]=[CH:45][CH:44]=1.CN1CCOCC1>CN(C=O)C.CCOC(C)=O>[C:43]1([C:49]2[N:50]=[C:51]([C:54]3([CH2:60][NH:61][C:13](=[O:15])[C:12]4[CH:16]=[C:8]([C:5]5[N:4]=[C:3]([C:2]([F:1])([F:18])[F:17])[O:7][N:6]=5)[CH:9]=[N:10][CH:11]=4)[CH2:55][CH2:56][O:57][CH2:58][CH2:59]3)[S:52][CH:53]=2)[CH:44]=[CH:45][CH:46]=[CH:47][CH:48]=1

Komponenten

7

Edukt 4

HCID 79724-MethylmorpholineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 67322930(4-(4-phenylthiazol-2-yl)tetrahydro-2H-pyran-4-yl)methanamineHCID 673242165-(5-(Trifluoromethyl)-1,2,4-oxadiazol-3-yl)nicotinic acid

Produkt 1

HCID 67324123N-((4-(4-phenylthiazol-2-yl)tetrahydro-2H-pyran-4-yl)methyl)-5-(5-(trifluoromethyl)-1,2,4-oxadiazol-3-yl)nicotinamideAusbeute 37 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 6228DimethylformamideLösungsmittelHCID 8857Ethyl AcetateLösungsmittel

Versuchsvorschrift

To a stirred solution of compound 5-(5-(trifluoromethyl)-1,2,4-oxadiazol-3-yl)nicotinic acid (100 mg, 0.4 mmol) in dry DMF (5 mL) were added HATU (180 mg, 0.46 mmol) followed by hydrochloride salt of (4-(4-phenylthiazol-2-yl)tetrahydro-2H-pyran-4-yl)methanamine (120 mg, 0.4 mmol) and NMM (0.12 mL, 1.1 mmol) at 0° C. The reaction mixture was slowly warmed to room temperature and stirred for further 10 h. The reaction mixture was diluted with EtOAc. The organic layer was washed with water and brine solution, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The crude product was purified by column chromatography (silica 60-120 mesh, eluent 50-60% EtOAc in petroleum ether) to get pure product N-((4-(4-phenylthiazol-2-yl)tetrahydro-2H-pyran-4-yl)methyl)-5-(5-(trifluoromethyl)-1,2,4-oxadiazol-3-yl)nicotinamide (70 mg, yield 37%): 1H NMR (400 MHz, CDCl3) δ 9.43 (d, J=2 Hz, 1H), 9.21 (br s, 1H), 8.76 (br s, 1H), 7.87 (d, J=7 Hz, 2H), 7.75 (br s, 1H), 7.53 (s, 1H), 7.41-7.32 (m, 3H), 3.99-3.95 (m, 2H), 3.79-3.74 (m, 2H), 2.35-2.32 (m, 2H), 2.07-2.03 (m, 2H). MS (ESI) m/z: Calculated for C24H20F3N5O3S: 515.12. found: 516.0 (M+H)+.

Aufarbeitung

  1. washThe organic layer was washed with water and brine solution
  2. dry with materialdried over anhydrous sodium sulfate
  3. concentrationconcentrated under reduced pressure
  4. customThe crude product was purified by column chromatography (silica 60-120 mesh, eluent 50-60% EtOAc in petroleum ether)

Quellen und Nachweise

ORD-Eintrag
ord-7199b52935cb4395bbc20810cb2d8fda
Quelldatensatz
uspto-grants-2014_12
Patentnummer
US08901156B2

Notizen zur Reaktion

Wird geladen…