Reacción #9823

Ecuación de reacción

3-(2-bromo-phenyl)-3,4-dihydro-7-methanesulphonyl-1-methyl-pyrimido[4,5-d]pyrimidin-2(1H)-one

hydroxymethyl-6-amino-1,4-benzodioxane

material b

hydroxymethyl-6-amino-1,4-benzodioxane

HCl

TFA

→

title product

3-(2-bromo-phenyl)-7-(2-hydroxymethyl-2,3-dihydro-benzo[1,4]dioxin-6-ylamino)-1-methyl-3,4-dihydro-1H-pyrimido[4,5-d]pyrimidin-2-one

Disolventes

NMP

Condiciones de reacción

Tratamiento posterior

1. 1
   Extracciónextracted with ethyl acetate
2. 2
   Extracciónextracted with CH2Cl2
3. 3
   Otroevaporated
4. 4
   Otrowas suspended in CH2Cl2 at room temperature
5. 5
   Filtraciónsolid impurities were filtered off
6. 6
   LavadoThe filtrate was washed again with water
7. 7
   Otroto remove remainders of NMP
8. 8
   Otroevaporated
9. 9
   OtroThe residue was triturated with water
10. 10
    Filtraciónfiltered
11. 11
    Otrodried

Procedimiento

1.2 g 3-(2-bromo-phenyl)-3,4-dihydro-7-methanesulphonyl-1-methyl-pyrimido[4,5-d]pyrimidin-2(1H)-one and 1.54 g 2 hydroxymethyl-6-amino-1,4-benzodioxane (starting material b)) were mixed in 20 ml NMP. 0.348 g TFA were added and the mixture was heated to 140° C. for 7 hrs. The mixture was poured into 10% aqueous HCl and extracted with ethyl acetate. The aqueous phase was adjusted to pH>9 and extracted with CH2Cl2. The organic phases were combined and evaporated. The residue was suspended in CH2Cl2 at room temperature and solid impurities were filtered off. The filtrate was washed again with water to remove remainders of NMP, then evaporated. The residue was triturated with water, filtered and dried to give 0.6 g of the title product (mp: 156–158° C.). NMR (CDCl3, δ in ppm): 2.03 (broad s, 1 H); 3.48 (s, 3H); 3.89 (dd, 1H); 3.95 (dd, 1H); 4.15 (dd, 1H); 4.28 (m, 1H); 4.33 (dd, 1H); 4.55 (d, 1H); 4.71 (d, 1H); 6.89 (m, 1H); 6.98 (m, 2H); 7.25 (m, 1H); 7.40 (m, 3H); 7.71 (d, 1H); 7.98 (s, 1H). MS (APCI+): 498 (M+1), 420 (M-Br)

Fuente