| 主权项 |
1. A process for preparing a dihydropyrimidine compound having Formula (I), or a tautomer thereof having Formula (Ia), wherein each R1 and R2 is independently F or Cl; R3 is C1-4 alkyl; Z is —O—, —S—, —S(═O)t—, or —N(R4)—; Y is —O—, —S—, —S(═O)t—, —(CH2)q—, or —N(R5)—; each t and q is independently 0, 1, or 2; each of R4 and R5 is independently H or C1-4 alkyl; each R6 is independently H, deuterium, halo, C1-4 alkyl, C1-4 haloalkyl, amino, C1-4 alkylamino, C1-4 alkoxy, nitro, triazolyl, tetrazyl, —(CR7R7a)m—OH, —S(═O)qOR8a, —(CR7R7a)m—S(═O)qN(R8a)2, —(CR7R7a)t—N(R8a)2, —(CR7R7a)m—C(═O)O—R8, —(CR7R7a)m—C(═O)O—(CR7R7a)m—OC(═O)O—R8, —(CR7R7a)m—C(═O)O—(CR7R7a)m—OC(═O)—R8, —(CR7R7a)m—C(═O)O—(CR7R7a)m—C(═O)O—R8, —(CR7R7a)m—OC(═O)—R8, or —(CR7R7a)m—C(═O)—N(R8R8a); each R7a and R7 is independently H, halo, C1-4 alkyl, C1-4 haloalkyl, —(CH2)m—OH, or —(CH2)m—C(═O)O—R8; or R7a and R7, together with the carbon atom to which they are attached, form a C3-6 cycloalkyl group, C2-9 heterocyclyl group, or —(C═O)—; each R8 and R8a is independently H, C1-4 alkyl, amino-C1-4-alkyl, C1-4 alkoxy, C1-6 alkyl-S(═O)q—, C6-10 aryl, C1-9 heteroaryl, C3-6 cycloalkyl, C2-9 heterocyclyl, C6-10 aryl-C1-6-alkyl, C1-9 heteroaryl-C1-6-alkyl, C3-6 cycloalkyl-C1-4-alkyl, C2-9 heterocyclyl-C1-6-alkyl, C2-9 heterocyclyl-S(═O)q—, C1-9 heteroaryl-S(═O)q—, C3-6 cycloalkyl-S(═O)q—, C6-10 aryl-S(═O)q—, —(CH2)m—OH, —(CH2)m—C(═O)O—(CH2)m—H, or —(CH2)m—OC(═O)—(CH2)m—H; each R9 is independently H, halo, C1-4 alkyl, C1-4 haloalkyl, C1-4 alkylthio, C3-6 cycloalkyl, —(CR7R7a)m—C(═O)—N(R8R8a), or —(CR7R7a)m—C(═O)O—R8; R10 is H or deuterium; n is 0, 1, 2, 3, 4, or 5; each m is independently 0, 1, 2, 3, or 4; f is 1, 2, 3, or 4; and j is 0, 1, or 2; wherein the process comprises the steps of: step (A): reacting an amidine compound of Formula (II), or a salt thereof with an aldehyde compound of Formula (III) and a compound of Formula (IVa) to obtain a compound of Formula (Va), wherein R3b is isopropoxy, propoxy, tert-butoxy, n-butoxy, 1-methyl-propoxy, n-pentyloxy, n-hexyloxy, C1-6 alkylamino, C3-6 cycloalkoxy, C3-6 cycloalkylamino, C1-6 alkyl-C3-6-cycloalkoxy, C6-10 arylamino, benzylamino, or benzyloxy; and R3a is H or C1-3 alkyl; step (B): halogenating the compound of Formula (Va) to form a halide; and then reacting the halide with a compound of Formula (VI), or a salt thereof to obtain a compound of Formula (VIIa),and
step (C): forming the compound of Formula (I) or Formula (Ia) from the compound of Formula (VIIa) by means of a transesterification. |
