Process for the manufacture of dihydropteridinones

A Process for preparing dihydropteridinones of general formula (I)

• wherein
• R1, R2 which may be identical or different, denote hydrogen or optionally substituted C1-C6-alkyl,
• or
• R1 and R2 together denote a 2- to 5-membered alkyl bridge which may contain 1 to 2 heteroatoms,
• R3 denotes hydrogen or a group selected from among optionally substituted C1-C12-alkyl, C2-C12-alkenyl, C2-C12-alkynyl and C6-C14-aryl, or
• a group selected from among optionally substituted and/or bridged C3-C12-cycloalkyl, C3-C12-cycloalkenyl, C7-C12-polycycloalkyl, C7-C12-polycycloalkenyl, C5-C12-spirocycloalkyl, C3-C12-heterocycloalkyl which contains 1 to 2 heteroatoms, and
• C3-C12-heterocycloalkenyl which contains 1 to 2 heteroatoms, or
• R1 and R3 or R1 and R3 together denote a saturated or unsaturated C3-C4-alkyl bridge which may optionally contain 1 heteroatom,
• R4 denotes a group selected from among hydrogen, —CN, hydroxy, —NR6R7 and halogen,
• or
• a group selected from among optionally substituted C1-C6-alkyl, C2-C6-alkenyl, C2-C6-alkynyl, C1-C5-alkyloxy, C2-C5-alkenyloxy, C2-C5-alkynyloxy, C1-C6-alkylthio, C1-C6-alkylsulphoxo and C1-C6-alkylsulphonyl,
• L denotes a linker selected from among optionally substituted C2-C10-alkyl, C2-C10-alkenyl, C6-C14-aryl, —C2-C4-alkyl-C6-C14-aryl, —C6-C14-aryl-C1-C4-alkyl, optionally bridged C3-C12-cycloalkyl and heteroaryl which optionally contains 1 or 2 nitrogen atoms,
• n denotes 0 or 1
• m denotes 1 or 2
• R5 denotes a group selected from among optionally substituted morpholinyl, piperidinyl, piperazinyl, piperazinylcarbonyl, pyrrolidinyl, tropenyl, R5-diketomethylpiperazinyl, sulphoxomorpholinyl, sulphonylmorpholinyl, thiomorpholinyl, —NR8R9 and azacycloheptyl,
• R6, R7, which may be identical or different, denote hydrogen or C1-C4-alkyl, and
• R8, R9 denotes unsubstituted nitrogen substituents at R5, which may be identical or different, either hydrogen or a group selected from among C1-C6-alkyl, —C1-C4-alkyl-C3-C10-cycloalkyl, C3-C10-cycloalkyl, C6-C14-aryl, —C1-C4-alkyl-C6-C14-aryl, pyranyl, pyridinyl, pyrimidinyl, C1-C4-alkyloxycarbonyl, C6-C14-arylcarbonyl, C1-C4-alkylcarbonyl, C6-C14-arylmethyloxycarbonyl, C6-C14-arylsulphonyl, C1-C4-alkylsulphonyl and C6-C14-aryl-C1-C4-alkylsulphonyl,
• comprising:
• reacting a compound of formula (II)
• wherein
• R1 to R3 are defined as specified and A is a leaving group,
• with a compound of formula (III)
• wherein
• R4, R5, L and m, n may be defined as specified, and subsequently isolating the product.