Reaktion #1592050

Reaktionsgleichung

tert-butyl {(1S,2R)-2-[(5-bromo-6-cyanopyridin-3-yl)amino]cyclohexyl}carbamate

6-amino-2-methylpyridine-3-carbonitrile

2-dicyclohexylphosphino-2′,4′,6′-triisopropylbiphenyl

cesium carbonate

→

tert-butyl [(1S,2R)-2-({6-cyano-5-[(5-cyano-6-methylpyridin-2-yl)amino]pyridin-3-yl}amino)cyclohexyl]carbamate

Reaktionsbedingungen

Aufarbeitung

1. 1
   workup.ADDITIONwas added
2. 2
   Sonstigedegassed dioxane (3 mL)
3. 3
   TemperaturThe reaction mixture was cooled to room temperature
4. 4
   workup.ADDITIONdiluted with ethyl acetate and water
5. 5
   Sonstigethe organic layer was separated
6. 6
   Trocknendried over magnesium sulfate
7. 7
   Filtrationfiltered
8. 8
   Einengenconcentrated under reduced pressure
9. 9
   SonstigePurification by chromatography on silica gel (0-40% ethyl acetate/hexanes, linear gradient)

Vorschrift

To a flask containing tert-butyl {(1S,2R)-2-[(5-bromo-6-cyanopyridin-3-yl)amino]cyclohexyl}carbamate (PrepEx 1.1) (120 mg, 0.30 mmol), 6-amino-2-methylpyridine-3-carbonitrile (40 mg, 0.30 mmol), 2-dicyclohexylphosphino-2′,4′,6′-triisopropylbiphenyl (29 mg, 0.061 mmol), Pd2(dba)3 (28 mg, 0.031 mmol) and cesium carbonate (198 mg, 0.609 mmol) was added degassed dioxane (3 mL). The reaction mixture was heated to 100° C. overnight. The reaction mixture was cooled to room temperature, diluted with ethyl acetate and water, and the organic layer was separated, dried over magnesium sulfate, filtered, and concentrated under reduced pressure. Purification by chromatography on silica gel (0-40% ethyl acetate/hexanes, linear gradient) afforded tert-butyl [(1S,2R)-2-({6-cyano-5-[(5-cyano-6-methylpyridin-2-yl)amino]pyridin-3-yl}amino)cyclohexyl]carbamate. MS ESI calc'd for C24H30N7O2 [M+H]+ 448. found 448. 1H NMR (500 MHz, DMSO-d6) δ 9.62 (s, 1H), 7.92-7.86 (m, 2H), 7.26 (s, 1H), 6.81 (d, J=8.8 Hz, 1H), 6.64 (d, J=8.5 Hz, 1H), 6.56 (d, J=7.7 Hz, 1), 3.75-3.64 (m, 2H), 2.47 (s, 3H), 1.75-1.42 (m, 8H), 1.26 (s, 9H).

Quelle