Réaction #172050

Équation de réaction

(R)-2-(6-chloro-5-cyanopyridin-2-ylamino)butanamide

(R)-6-(1-amino-1-oxobutan-2-ylamino)-2-(quinolin-3-ylamino)nicotinamide

6-aminoquinoline

cesium carbonate

BINAP

→

(R)-2-(5-cyano-6-(quinolin-6-ylamino)pyridin-2-ylamino)butanamide

Solvants

dioxane

Conditions de réaction

Traitement

1. 1
   Autrewas degassed with Ar
2. 2
   ConcentrationIt was concentrated in vacuo
3. 3
   Lavagewashed with brine
4. 4
   Autredried
5. 5
   Concentrationconcentrated in vacuo

Mode opératoire

The mixture of (R)-2-(6-chloro-5-cyanopyridin-2-ylamino)butanamide (compound J52 in Example 203) (140 mg, 0.59 mmol), 6-aminoquinoline (260 mg, 1.8 mmol), cesium carbonate (980 mg, 3.0 mmol), BINAP (75 mg, 0.12 mmol) and Pd(OAc)2 (27 mg, 0.12 mmol) in 20 mL dioxane was degassed with Ar. The mixture was stirred under Ar at 105° C. for overnight. It was concentrated in vacuo, taken into EtOAc, washed with brine, dried, concentrated in vacuo and subjected to flash column (0 to 8% MeOH in DCM) to isolate (R)-2-(5-cyano-6-(quinolin-6-ylamino)pyridin-2-ylamino)butanamide. It was then dissolved in 4 mL DMSO. To it were added 100 mg powder K2CO3 and 2 mL 50% H2O2 in water. The mixture was stirred at RT for 1 h. To it was added 4 mL water, the mixture was vigorously stirred and subjected to reverse phase preparative HPLC to isolate the title compound (65 mg). UV: 267, 299, 330 nm. M+H found for C19H20N6O2: 365.2. NMR (CD3OD): 9.25 (1H, d, J=8.8 Hz), 9.04 (1H, d, J=2.0 Hz), 8.85 (1H, dd, J=6.4; 2.4Hz), 8.06 (1H, d, J=9.6 Hz), 7.99 (1H, dd, J=9.2; 2.41 Hz), 7.92 (1H, m), 7.88 (1H, d, J=8.8 Hz), 6.28 (1H, d, J=9.2 Hz), 4.31 (1H, m), 2.00 (2H, m), 1.14 (3H, t, J=7.6 Hz) ppm.

Source