1-Ethyl-1h-pyrazol-4-amine → (1-Ethyl-1H-pyrazol-4-yl)-[8-(4-methanesulfonyl-phenoxy)-[1,2,4]triazolo[1,5-a]pyridin-2-yl]-amine
Reaktionsgleichung
Cl[C:2]1[N:21]=[C:5]2[C:6]([O:10][C:11]3[CH:16]=[CH:15][C:14]([S:17]([CH3:20])(=[O:19])=[O:18])=[CH:13][CH:12]=3)=[CH:7][CH:8]=[CH:9][N:4]2[N:3]=1.[CH2:22]([N:24]1[CH:28]=[C:27]([NH2:29])[CH:26]=[N:25]1)[CH3:23]>>[CH2:22]([N:24]1[CH:28]=[C:27]([NH:29][C:2]2[N:21]=[C:5]3[C:6]([O:10][C:11]4[CH:16]=[CH:15][C:14]([S:17]([CH3:20])(=[O:19])=[O:18])=[CH:13][CH:12]=4)=[CH:7][CH:8]=[CH:9][N:4]3[N:3]=2)[CH:26]=[N:25]1)[CH3:23]Komponenten
Versuchsvorschrift
A well stirred mixture of 2-amino-[1,2,4]triazolo[1,5-a]pyridine-8-ol (0.300 g, 2.00 mmol), 1-fluoro-4-methanesulfonyl-benzene (0.418 g, 2.40 mmol), N,N-dimethylacetamide (2 mL) and potassium tert-butoxide (0.448 g, 4.00 mmol) was heated at 130° C. for 18 h under an argon atmosphere. The reaction mixture was evaporated in vacuo and partitioned between dichloromethane and saturated aqueous sodium bicarbonate solution. The aqueous phase was extracted twice with dichloromethane and the combined organic layers were washed with brine, dried over sodium sulfate, filtered, and evaporated in vacuo to furnish a crude product. The crude product was purified by preparative Gilson HPLC method to yield a pure product, which was triturated from a mixture of dichloromethane, methanol, ether and hexane. 8-(4-Methanesulfonyl-phenoxy)-[1,2,4-triazolo[1,5-a]pyridin-2-ylamine was isolated as a white solid (125 mg, 20%). MP=245-247° C. 1H NMR (400 MHz, (D3C)2SO, δ, ppm): 8.53 (d, J=6.56 Hz, 1H), 7.87 (d, J=8.77 Hz, 2H), 7.36 (d, J=7.73 Hz, 1H), 7.15 (d, J=8.76 Hz, 2H), 6.92 (t, J=7.28 Hz, 1H), 6.13 (s, 1H), 3.19 (s, 3H). MS=305 (MH)+. 211b) 2-Chloro-8-(4-methanesulfonyl-phenoxy)-[1,2,4]triazolo[1,5-a]pyridine was prepared in a manner analogous to Example 68a. Product was isolated as a yellow solid (0.455 g, 80%). MP=202-204° C. 1H NMR (400 MHz, (D3C)2SO, δ, ppm): 8.44 (d, J=6.77 Hz, 1H), 7.98 (d, J=8.08 Hz, 2H), 7.21 (t, J=7.76 Hz, 3H), 7.08 (t, J=7.52 Hz, 1H), 3.09 (s, 3H). MS=324 (MH)+. 211c) (1-Ethyl-1H-pyrazol-4-yl)-[8-(4-methanesulfonyl-phenoxy)-[1,2,4]triazolo[1,5-a]pyridin-2-yl]-amine was prepared from 2-chloro-8-(4-methanesulfonyl-phenoxy)-[1,2,4]triazolo[1,5-a]pyridine (0.065 g, 0.20 mmol) and 1-ethyl-1H-pyrazol-4-ylamine (0.029 g, 0.26 mmol) in a manner analogous to Example 2d. Product was isolated as a tan solid (45 mg, 56%). MP=183-185° C. 1H NMR (400 MHz, (D3C)2SO, δ, ppm): 9.27 (s, 1H), 8.67 (d, J=6.51 Hz, 1H), 7.89 (d, J=7.72 Hz, 2H), 7.68 (s, 1H), 7.45 (d, J=7.74 Hz, 1H), 7.35 (s, 1H), 7.22 (d, J=7.29 Hz, 2H), 7.00 (t, J=7.29 Hz, 1H), 4.055 (q, J=7.18 Hz, 2H), 3.20 (s, 3H), 1.32 (t, J=7.06 Hz, 3H). MS=399 (MH)+.
Quellen und Nachweise
- ORD-Eintrag
- ord-702354423005495da80054fe579162f2
- Quelldatensatz
- uspto-grants-2013_08
- Patentnummer
- US08501936B2
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