Dimethylformamide → 3-(methyl((3-(5-phenyl-4-(trifluoromethyl)isoxazol-3-yl)-4,5-dihydronaphtho[1,2-c]isoxazol-7-yl)methyl)amino)propanamide TFA

HRID 1506461Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1506461
Br[CH2:2][C:3]1[CH:4]=[C:5]2[C:28](=[CH:29][CH:30]=1)[C:9]1=[N:10][O:11][C:12]([C:13]3[C:17]([C:18]([F:21])([F:20])[F:19])=[C:16]([C:22]4[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=4)[O:15][N:14]=3)=[C:8]1[CH2:7][CH2:6]2.[CH3:31][NH:32][CH2:33][CH2:34][C:35]([NH2:37])=[O:36].C(N(CC)CC)C.CN([CH:48]=[O:49])C>C(OCC)(=O)C>[OH:36][C:48]([C:18]([F:21])([F:20])[F:19])=[O:49].[CH3:31][N:32]([CH2:2][C:3]1[CH:4]=[C:5]2[C:28](=[CH:29][CH:30]=1)[C:9]1=[N:10][O:11][C:12]([C:13]3[C:17]([C:18]([F:21])([F:20])[F:19])=[C:16]([C:22]4[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=4)[O:15][N:14]=3)=[C:8]1[CH2:7][CH2:6]2)[CH2:33][CH2:34][C:35]([NH2:37])=[O:36]

Komponenten

6

Edukt 4

HCID 6228DimethylformamideHCID 8471TriethylamineHCID 22182162N~3~-Methyl-beta-alaninamideHCID 671678437-(Bromomethyl)-3-(5-phenyl-4-(trifluoromethyl)isoxazol-3-yl)-4,5-dihydronaphtho[1,2-c]isoxazole

Produkt 1

HCID 866699153-(methyl((3-(5-phenyl-4-(trifluoromethyl)isoxazol-3-yl)-4,5-dihydronaphtho[1,2-c]isoxazol-7-yl)methyl)amino)propanamide TFAAusbeute 48 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 8857Ethyl AcetateLösungsmittel

Versuchsvorschrift

A mixture of 7-(bromomethyl)-3-(5-phenyl-4-(trifluoromethyl)isoxazol-3-yl)-4,5-dihydronaphtho[1,2-c]isoxazole (6C, 0.025 g, 0.053 mmol), 3-(methylamino)propanamide (5.37 mg, 0.053 mmol) and triethylamine (7.33 mL, 0.053 mmol) in DMF (3.0 mL) was stirred at room temperature overnight. The reaction mixture was diluted with ethyl acetate (15 mL) and washed with water (3×1.0 mL). The ethyl acetate extract was concentrated, and the residue was chromatographed using reverse-phase preparative HPLC (Column: LUNA 5 u C18, 21×100 mm:Solvent MeOH(B)—H2O(A), 0.1% TFA: 0% B-100% B, Gradient Time 12 min, Stop Time 20 min, Flow Rate 20 ml/min, Wavelength 220 nM) to give 3-(methyl((3-(5-phenyl-4-(trifluoromethyl)isoxazol-3-yl)-4,5-dihydronaphtho[1,2-c]isoxazol-7-yl)methyl)amino)propanamide TFA (0.012 g., 0.493 mmol, 48%) as a viscous tan liquid. The product had an HPLC ret. time=4.02 min. (condition B). LC/MS M+1=497.07. 1H NMR (400 MHz, CD3OD) δ ppm 8.09 (1H, d, J=7.92 Hz), 7.79 (2H, d, J=7.26 Hz), 7.32-7.77 (5H, m), 4.54 (2H, s), 3.23-3.44 (4H, m), 2.98-3.21 (4H, m), and 2.89 (3H, s).

Aufarbeitung

  1. washwashed with water (3×1.0 mL)
  2. extractionThe ethyl acetate extract
  3. concentrationwas concentrated
  4. customthe residue was chromatographed
  5. customreverse-phase preparative HPLC (Column: LUNA 5 u C18, 21×100 mm:Solvent MeOH(B)—H2O(A), 0.1% TFA: 0% B-100% B, Gradient Time 12 min, Stop Time 20 min, Flow Rate 20 ml/min, Wavelength 220 nM)

Quellen und Nachweise

ORD-Eintrag
ord-908972ae395241c2824fe1f6af27442d
Quelldatensatz
uspto-grants-2015_12
Patentnummer
US09216972B2

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