Reaktion #9823

Reaktionsgleichung

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

Lösungsmittel

NMP

Reaktionsbedingungen

Aufarbeitung

1. 1
   Extraktionextracted with ethyl acetate
2. 2
   Extraktionextracted with CH2Cl2
3. 3
   Sonstigeevaporated
4. 4
   Sonstigewas suspended in CH2Cl2 at room temperature
5. 5
   Filtrationsolid impurities were filtered off
6. 6
   WaschenThe filtrate was washed again with water
7. 7
   Sonstigeto remove remainders of NMP
8. 8
   Sonstigeevaporated
9. 9
   SonstigeThe residue was triturated with water
10. 10
    Filtrationfiltered
11. 11
    Sonstigedried

Vorschrift

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)

Quelle