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 1397212Notes

Reaction equation

HRID 1397212 reaction equation
[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

Participants

7

Reactant 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

Product 1

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

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

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)+.

Workup

  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)

Sources & evidence

ORD record
ord-7199b52935cb4395bbc20810cb2d8fda
Source dataset
uspto-grants-2014_12
Patent number
US08901156B2

Reaction notes

Loading…