Preparation method for pyrimidine-2-amine

A method of preparing a cyclic (2-enamino)pyrimidine compound, the method comprising:

• 1) Oxidizing a pyrimidine compound of the following Chemical Formula 2 to prepare a pyrimidine-N-oxide intermediate;
• 2) Following step 1), in-situ activating the pyrimidine-N-oxide intermediate in the presence of a trifluoromethanesulfonic anhydride and reacting with a pyridine reagent of the following Chemical Formula 3-2 to prepare a pyrimidine-2-pyridinium salt;
• and
• 3) Following step 2), partially reducing the pyrimidine-2-pyridinium salt to prepare a cyclic (2-enamino)pyrimidine compound of the following Chemical Formula 1-2,
• wherein steps 1) and 2) are performed as in-situ continuous processes without a separation process:
• wherein
• R1, R2, and R3 are independently of one another hydrogen, C1-C20 alkyl, C3-C20 cycloalkyl, C6-C20 aryl, C1-C20 alkoxy, C2-C20 alkenyl, C3-C20 heteroaryl, or —NR′C(±O)Ar1, or R1 to R3 may be linked to an adjacent substituent to form a ring;
• R5 is halo C1-C20 alkyl, cyano, C1-C20 alkylcarbonyl, or C6-C20 arylcarbonyl;
• R′ is hydrogen or C1-C20 alkyl;
• Ar1 is C6-C20 aryl or C3-C20 heteroaryl;
• the alkyl, cycloalkyl, aryl, alkoxy, alkenyl, and heteroaryl of R1 to R3 may be further substituted by any one or more selected from C1-C20 alkyl, halogen, C1-C20 alkoxy, hydroxy, C6-C20 aryl, halo C6-C20 aryl, —OSiRa1Ra2Ra3, -L1-NRb1-L2-Rb2, and −CHRc1Rc2;
• Ra1, Ra2, and Ra3 are independently of one another C1-C20 alkyl, C3-C20 cycloalkyl, or C6-C20 aryl;
• L1 is C6-C20 arylene or halo C6-C20 arylene, and L2 is SO2 or C═O;
• Rb1 is hydrogen or C1-C20 alkyl;
• Rb2 is C1-C20 alkoxy, C6-C20 aryl, or halo C6-C20 aryl;
• Rc1 is C3-C20 cycloalkyl;
• and
• Rc2 is -L3-Rd1, L3 is C1-C20 alkylene, and Rai is cyano, halogen, or nitro.

A method of preparing a pyrimidin-2-substituted amine compound, the method comprising:

• 1) Oxidizing a pyrimidine compound of the following Chemical Formula 2 to prepare a pyrimidine-N-oxide intermediate;
• 2) Following step 1), reacting the pyrimidine-N-oxide intermediate with an imidoyl chloride compound of the following Chemical Formula 4-1 in the presence of a trifluoromethanesulfonic anhydride to prepare a pyrimidin-2-iminium salt;
• and
• 3) Following step 2), treating the pyrimidin-2-iminium salt with sodium bicarbonate, or reducing or hydrolyzing the pyrimidin-2-iminium salt to prepare a pyrimidin-2-substituted amine compound of the following Chemical Formula 1-3,
• wherein steps 1) and 2) are performed as in-situ continuous processes without a separation process:
• wherein
• R1, R2, and R3 are independently of one another hydrogen, C1-C20 alkyl, C3-C20 cycloalkyl, C6-C20 aryl, C1-C20 alkoxy, C2-C20 alkenyl, C3-C20 heteroaryl, or —NR′C(═O) Ar1, or R1 to R3 may be linked to an adjacent substituent to form a ring;
• R″ is hydrogen, —C(═O) R12, or —CH2R12;
• R11 is C1-C20 alkyl, C6-C20 aryl, allyl, haloC1-C20 alkyl, C6-C20 aryl C1-C20 alkyl, or C3-C20 cycloalkyl, and the cycloalkyl may be further substituted by one or more selected from halogen, halo C1-C20 alkyl, and halo C6-C20 aryl;
• R12 is C1-C20 alkyl or C6-C20 aryl;
• R′ is hydrogen or C1-C20 alkyl;
• Ar1 is C6-C20 aryl or C3-C20 heteroaryl;
• the alkyl, cycloalkyl, aryl, alkoxy, alkenyl, and heteroaryl of R1 to R3 may be further substituted by any one or more selected from C1-C20 alkyl, halogen, C1-C20 alkoxy, hydroxy, C6-C20 aryl, halo C6-C20 aryl, —OSiRa1Ra2Ra3, -L1-NRb1-L2-Rb2, and —CHRc1Rc2;
• Ra1, Ra2, and Ra3 are independently of one another C1-C20 alkyl, C3-C20 cycloalkyl, or C6-C20 aryl;
• L1 is C6-C20 arylene or halo C6-C20 arylene, and L2 is SO2 or C═O;
• Rb1 is hydrogen or C1-C20 alkyl;
• Rb2 is C1-C20 alkoxy, C6-C20 aryl, or halo C6-C20 aryl;
• Rc1 is C3-C20 cycloalkyl;
• and
• Rc2 is -L3-Rd1, L3 is C1-C20 alkylene, and Rai is cyano, halogen, or nitro.