Preparation of aminopyrimidine compounds
AssigneeAstraZeneca UK Limited
InventorsAkio Matsushita, Mizuho Oda, Yasuhiro Kawachi, Jun-ichi Chika
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Abstract
A 2-(N-methyl-N-methanesulfonylamino)pyrimidine compound of the formula (3): [R is a hydrocarbyl group], is prepared by the steps of: (I) reacting an isobutyrylacetate ester with 4-fluorobenzaldehyde and urea in the presence of a protonic compound and a metal salt; (II) oxidizing the reaction product of the step (I); (III) reacting the oxidation product of the step (II) with an organic sulfonyl halide or an organic sulfonyl anhydride; and (IV) reacting the reaction product of the step (III) with N-methyl-N-methanesulfonamide. 1
Claims38
A process for preparing a 2-(N-methyl-N-methanesulfonylamino)pyrimidine compound having the formula (3):
- 18
- in which R is a hydrocarbyl group,
- which comprises the steps of:
- reacting a hydroxypyrimidine conmpound having the formula (1):
- 19
- in which r is the same as above,
- with an organic sulfonyl halide having the formula (2):
- R′SO2X (2)
- in which R′ is a hydrocarbyl group and X is a halogen atom, or an organic sulfonic anhydride having the formula (2a):
- (R′SO2)2O (2a)
- in which R′ has the same meaning as above, and
- reacting the resulting reaction product with N-methyl-N-methanesulfonamide.
A hydroxypyrimidine compound having the formula (1):
- 22
- in which R is a hydrocarbyl group.
A dihydropyrimidinone compound having the formula (4):
- 25
- wherein R is a hydrocarbyl group.
A method for preparing an aminopyrimidine compound having the formula (8):
- 27
- wherein R is a hydrocarbyl group, and each of R1 and R2 independently is hydrogen atom, an alkyl group, an alkylsulfonyl group, or an arylsulfonyl group, which comprises reacting a 2-substituted pyrimidine compound having the formula (6):
- 28
- wherein R is the same as above, and X is a halogen atom or an organic sulfonyloxy group,
- with an amine compound having the formula (7):
- 29
- wherein each of R1 and R2 is the same as above.
A halogenopyrimidine compound having the formula (9):
- 30
- wherein R is a hydrocarbyl group, and Hal is a halogen atom.
An organic sulfonyloxypyrimidine compound having the formula (10):
- 32
- wherein each of R and R′ independently is a hydrocarbyl group
A process for preparing a 2-(N-methyl-N-methanesulfonylamino)pyrimidine compound having the formula (3):
- 34
- in which R is a hydrocarbyl group,
- which comprises the steps of:
- (I) reacting an isobutyrylacetate ester of the following formula (5):
- 35
- wherein R is a hydrocarbyl group.
- with 4-fluorobenzaldehyde and urea in the presence of a protonic compound and a metal salt;
- (II) oxidizing the reaction product of the step (I);
- (III) reacting the oxidation product of the step (II) with an organic sulfonyl halide having the formula is (2):
- R′SO2X (2)
- in which R′ is a hydrocarbyl group, and X is a halogen atom, or an organic sulfonic anhydride having the formula (2a):
- (R′SO2)2O (2a)
- in which R′ has the same meaning as above;
- and
- (IV) reacting the reaction product of the step (III) with N-methyl-N-methanesulfonamide.
Dependencies are inferred from the claim text.