Process for the manufacture of dihydropteridinones
Disclosed are processes for preparing dihydropteridinones of general formula (I) wherein the groups L and R 1 -R 5 have the meanings given in the claims and in the specification.
1. A Process for preparing dihydropteridinones of the general formula (I)
wherein the dihydropteridinone is selected from among the following dihydropteridinones of general formula (I)
config. R 1
Ex.
R 1
R 2
or R 2
R 3
27
H
R
44
H
R
55
H
R
58
H
R
102
H
R
103
H
R
105
H
R
110
H
R
115
H
R
133
H
R
134
H
R
234
H
R
240
H
R
Ex.
R 4
L n —R 5 m
27
44
H
55
58
102
103
105
110
115
133
134
234
240
while the abbreviations X 1 , X 2 , X 3 , X 4 and X 5 used in the Table in each case denote a link to a position in the general formula listed in the Table instead of the corresponding groups R 1 , R 2 , R 3 , R 4 and L n -R 5 m ;
comprising:
reacting a compound of formula (II)
wherein
R 1 to R 3 are defined as specified and A is a leaving group,
with a compound of formula (III)
wherein
R 4 , R 5 , L and m, n may be defined as specified, and subsequently isolating the product wherein the reaction is carried out in the presence of a organic sulphonic acids catalyst.
2. The Process according to claim 1 , wherein organic sulphonic acids are selected from among methanesulphonic acid, ethanesulphonic acid, ethane-1,2-disulphonic acid, benzenesulphonic acid or p-toluenesulphonic acid.
3. The Process according to claim 1 , wherein the reaction is carried out in a solvent chosen from dimethylformamide, dimethylacetamide, N-methylpyrrolidinone, 1,3-dimethyl-3,4,5,6-tetrahydro-2(1H)-pyrimidone (DMPU), dimethylsulphoxide, sulpholane, methanol, ethanol, 1-propanol, 1-butanol, 1-pentanol, 2-propanol, 2-butanol, an isomeric secondary alcohol of pentane or hexane, a tertiary alcohol of butane, pentane or hexane, acetonitrile and 2-propylnitrile.
4. The Process according to claim 3 , wherein the reaction temperature is between 18° C. and 180° C.