Reacción #663637

Ecuación de reacción

2-(2,6-dimethyl-4H-pyran-4-ylidene)malononitrile

2-(2,6-dimethyl-4H-pyran-4-ylidene) malononitrile

aldehyde

tert-butyl 4-formyl-2-methoxyphenylcarbamate

Piperidine

→

(E)-2-(2-(4-amino-3-methoxystyryl)-6-methyl-4H-pyran-4-ylidene)malononitrile

Disolventes

EtOH

Condiciones de reacción

Tratamiento posterior

1. 1
   OtroThe solvent was removed with a stream of N2
2. 2
   workup.DISSOLUTIONthe crude mixture was dissolved in EtOAc at 5 mg/ml
3. 3
   Otropurified by normal phase preparative
4. 4
   workup.ADDITIONThis compound was treated with a 4N HCl solution in dioxane (4 N, 1.3 ml) for 3 hrs
5. 5
   workup.ADDITIONThe mixture was diluted with hexanes
6. 6
   Lavadowashed with hexanes
7. 7
   Otrodried under vacuum

Procedimiento

A mixture of 2-(2,6-dimethyl-4H-pyran-4-ylidene)malononitrile (1, 20.7 mg, 0.12 mmol) and aldehyde 2c (25.1 mg, 0.1 mmol) were dissolved in anhydrous EtOH (0.67 ml) at 65° C. Piperidine (0.5 μl) was added and the mixture was stirred at 80° C. for 7 hours. The solvent was removed with a stream of N2, the crude mixture was dissolved in EtOAc at 5 mg/ml and purified by normal phase preparative HPLC using hexanes/ethyl acetate as eluent. Yield: 10.6 mg (26%). LCMS ESI+m/z 406 (M+H+) H-NMR (400 MHz, CD2Cl2): 8.16 (1H, d, J=8 Hz) 7.47 (1H, d, J=16 Hz) 7.29 (1H, s) 7.19 (1h, dd, J=8 Hz, 0.4 Hz) 7.1 (1H, d, J=0.4 Hz) 6.67-6.74 (2H, m) 6.56 (1H, m) 3.97 (3H, s) 2.43 (3H, s) 1.55 (9H, s). C-NMR (400 MHz, CD2Cl2) 163.02, 160.11, 157.01, 152.81, 148.32, 138.31, 131.33, 129.29, 122.99, 118.01, 116.81, 115.74, 108.45, 107.26, 106.77, 81.27, 56.35, 28.56, 20.31. This compound was treated with a 4N HCl solution in dioxane (4 N, 1.3 ml) for 3 hrs. The mixture was diluted with hexanes, the precipitate centrifuged, re-suspended and washed with hexanes, then dried under vacuum. LCMS ESI+ m/z: 306 (M+H+). H-NMR (400 MHz, CD2Cl2) 7.37 (1H, d, J=16 hz) 7.12 (1H, dd, J=16 Hz, 0.4 Hz) 7.02 (1H, d, J=0.4 Hz) 6.56-6.63 (3H, m) 6.12 (1H, m) 3.97 (3H, s) 2.42 (3H, s). C-NMR (400 MHz, CD2Cl2) 164.58, 156.12, 151.52, 140.90, 139.05, 129.73, 127.19, 121.74, 115.48, 110.73, 109.95, 102.81, 101.68, 100.79, 90.2, 55.89, 21.02.

Fuente