Reacción #58698

Ecuación de reacción

chloroacetonitrile

Acetonitrile

sodium bis(trimethylsilyl)amide

THF

Chloroacetonitrile

2-Chlorophenyl isothiocyanate

→

title compound

3-Amino-7-(2-chlorophenyl)-6-oxo-6,7-dihydrothieno[2,3-b]pyridine-2-carbonitrile

Disolventes

EtOH

Condiciones de reacción

Tratamiento posterior

1. 1
   Otroto give a thick white precipitate
2. 2
   Otroto give a brown solution
3. 3
   Temperaturathe mixture heated
4. 4
   Temperaturaat reflux for 24 h
5. 5
   OtroVolatiles were removed in vacuo
6. 6
   workup.DISSOLUTIONthe residue dissolved in acetonitrile (100 mL)
7. 7
   Temperaturathe mixture heated at 50° C. for 1 h
8. 8
   workup.ADDITIONwas added
9. 9
   Temperaturaheating
10. 10
    OtroSome of the acetonitrile (˜50 mL) was removed in vacuo and water
11. 11
    workup.ADDITIONwas added
12. 12
    Otroto precipitate the product
13. 13
    FiltraciónThe brown solid was filtered off
14. 14
    Lavadowashed with water (50 mL) and Et2O (50 mL)
15. 15
    Otrodried

Procedimiento

Acetonitrile (10 mL) was added to a solution of sodium bis(trimethylsilyl)amide (100 mL, 1.0M in THF, 100 mmol) in THF (50 mL) at −78° C. to give a thick white precipitate. 2-Chlorophenyl isothiocyanate (7.72 g, 45.45 mmol) was added to give a brown solution. The mixture was allowed to warm to r.t. over 1 h then diluted with EtOH (50 mL). N,N-Dimethyluracil (6.4 g, 45 mmol) was added and the mixture heated at reflux for 24 h. Volatiles were removed in vacuo and the residue dissolved in acetonitrile (100 mL). Chloroacetonitrile (2.85 mL, 45 mmol) was added and the mixture heated at 50° C. for 1 h, a second charge of chloroacetonitrile (2.85 mL, 45 mmol) was added and heating continued for 1.5 h. Some of the acetonitrile (˜50 mL) was removed in vacuo and water was added to precipitate the product. The brown solid was filtered off, washed with water (50 mL) and Et2O (50 mL) and dried to give the title compound as a brown solid (14.3 g, quant.). δH (DMSO-d6) 8.10 (1H, d, J 9.7 Hz), 7.75-7.73 (1H, m), 7.65-7.54 (3H, m), 7.14 (2H, br s, NH2), 6.54 (1H, d, J 9.7 Hz). LCMS (ES+) RT 2.97 minutes, 302 (M+H)+.

Fuente