Reacción #56794

Ecuación de reacción

sodium thiomethoxide

compound 10a

3-[2(R)-tert-butoxycarbonylamino-2-phenylethyl]-5-(2-fluoro-3-methoxyphenyl)-1-[2,6-difluorobenzyl]-6-methyl-pyrimidine-2,4(1H,3H)-dione

sodium thiomethoxide

→

compound 10b

Rendimiento 78.6%

3-[2(R)-tert-butoxycarbonylamino-2-phenylethyl]-5-(2-fluoro-3-methoxylphenyl)-1-[2-fluoro-6-methylthiobenzyl]-6-methyl-pyrimidine-2,4(1H,3H)-dione

Rendimiento 78.6%

Disolventes

DMSO

Condiciones de reacción

Tratamiento posterior

1. 1
   TemperaturaThe reaction mixture was heated to 1000 C under nitrogen for 1 hour
2. 2
   Temperaturathe reaction mixture was heated to 1000 C under nitrogen for 1 hour
3. 3
   TemperaturaThe reaction mixture was cooled
4. 4
   Otropartitioned between ethyl ether and water
5. 5
   LavadoThe organic layer was washed with saturated aqueous sodium bicarbonate solution and brine
6. 6
   Secadodried with sodium sulfate
7. 7
   Filtraciónfiltered
8. 8
   Concentraciónconcentrated
9. 9
   OtroThe crude product was purified with a flash chromatography on silica gel
10. 10
    Lavadoeluted with 50% ethyl acetate in hexane

Procedimiento

To a solution of compound 10a (33 g, 56 mmol) in dry DMSO (100 mL) was added sodium thiomethoxide (4.0 g, 56 mmol) under nitrogen. The reaction mixture was heated to 1000 C under nitrogen for 1 hour. Another 0.28 eq. of sodium thiomethoxide (1.1 g, 16 mmol) was added, and the reaction mixture was heated to 1000 C under nitrogen for 1 hour. The reaction mixture was cooled and partitioned between ethyl ether and water. The organic layer was washed with saturated aqueous sodium bicarbonate solution and brine, dried with sodium sulfate, filtered and concentrated. The crude product was purified with a flash chromatography on silica gel eluted with 50% ethyl acetate in hexane to yield compound 10b as a pale yellow solid (27 g, 44 mmol, 78%). HPLC-MS (CI) m/z=524.1 (M+H+-Boc), tR=3.134 (method 4). 1H NMR (CDCl3): 1.38 (s, 9H), 2.07 (s, 3H), 2.51 (s, 3H), 3.90 (s, 3H), 4.07-4.13 (m, 1H), 4.29-4.39 (m, 1H), 5.30-5.53 (m, 2H), 5.79-5.85 (m, 1H), 6.80-6.91 (m, 2H), 6.70 (dd, 1H), 7.06-7.15 (m, 2H), 7.22-7.41 (m, 6h ).

Fuente