Ammonia → 3-Aminomethyl-6-(2-cyclopropylmethylamino-thiazol-4-yl)-pyridine
Reaktionsgleichung
[CH:1]1([CH2:4][NH:5][C:6]2[S:7][CH:8]=[C:9]([C:11]3[CH:18]=[CH:17][C:14]([C:15]#[N:16])=[CH:13][N:12]=3)[N:10]=2)[CH2:3][CH2:2]1.N.[H][H]>[Ni].CO>[NH2:16][CH2:15][C:14]1[CH:13]=[N:12][C:11]([C:9]2[N:10]=[C:6]([NH:5][CH2:4][CH:1]3[CH2:3][CH2:2]3)[S:7][CH:8]=2)=[CH:18][CH:17]=1Komponenten
Reaktionsbedingungen
- Temperatur
- 40 °C
Versuchsvorschrift
Add 6-[2-(cyclopropylmethylamino)-thiazol-4-yl]-nicotinonitrile (2.0 g, 7.8 mmol), Raney Nickel (2.0 mL), and 2M ammonia in methanol (200 mL) to a pressure vessel under a nitrogen atmosphere. Pressurize the vessel to 60 psi with hydrogen, and stir the mixture for 6 h at 40° C. Filter the mixture through Celite® and concentrate in vacuo to an oil. Dissolve the oil in EtOAc (300 mL) and saturated ammonium hydroxide (50 mL). Stir the solution for 20 h in a sealed flask at room temperature. Collect the organic layer and concentrate in vacuo. Purify the crude mixture by SCX chromatography followed by chromatography on silica gel (150 g) eluting with DCM/2M ammonia in methanol (99:1 to 85:15 gradient) to obtain the title compound (1.05 g, 51%). MS (ES+) m/z: 261 (M+H)+.
Aufarbeitung
- filtrationFilter the mixture through Celite®
- concentrationconcentrate in vacuo to an oil
- dissolutionDissolve the oil in EtOAc (300 mL)
- stirringStir the solution for 20 h in a sealed flask at room temperature
- customCollect the organic layer
- concentrationconcentrate in vacuo
- customPurify the crude mixture by SCX chromatography
- washeluting with DCM/2M ammonia in methanol (99:1 to 85:15 gradient)
Quellen und Nachweise
- ORD-Eintrag
- ord-419a6b6d4fbd471097ca9e1e8522e50f
- Quelldatensatz
- uspto-grants-2014_03
- Patentnummer
- US08680091B2
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