| 主权项 |
1. A method of preparing a compound of Formula I:or pharmaceutically acceptable salt wherein:
Each of R1 and R2 is independently optionally substituted amine, optionally substituted C1-6 alkyl, optionally substituted C2-6 alkenyl, optionally substituted C2-6 alkynyl, optionally substituted aryl, optionally substituted C3-8 cycloalkyl, optionally substituted heteroaryl, or optionally substituted fully saturated or partially unsaturated 5-10 membered heterocyclic ring having 1-3 heteroatoms independently selected from N, O, or S; comprising the steps of: i) reacting a compound of Formula A with a compound of Formula B, wherein R3 is —F, and n is 3-5 to generate a compound of Formula C;wherein the reaction of step i) is performed in the presence of a base;
ii) reacting the compound of Formula C with a R1-reagent to generate a compound of Formula Dand
iii) reacting the compound of Formula D with a R2-reagent to generate the compound of Formula I,wherein
the R1-reagent is
HNR4aR5a wherein R4a is —H or C1-4 alkyl, and R5a is a mono- or bicyclic aryl, or a 6-10 membered mono- or bicyclic heteroaryl, wherein the aryl or heteroaryl group is optionally substituted; orHNR4bR5b wherein R4b is —H or C1-4 alkyl; R5b is C1-6 alkyl, C3-8 cycloalkyl, or a 3-8 membered fully saturated or partially unsaturated heterocyclic ring having 1-3 heteroatoms independently selected from N, O, or S, any of which are optionally substituted with 1-2 groups independently selected from aryl or a 6-10 membered mono- or bicyclic heteroaryl, or R4b and R5b taken together with the nitrogen atom to which they are attached form an optionally substituted 5-8 membered partially saturated or fully saturated heterocyclic ring having up to 1 additional heteroatom selected from N, O, or S; and the R2-reagent is
HNR8aR9a, wherein R8a is —H or C1-4 alkyl, and R9a is a mono- or bicyclic aryl, or a 6-10 membered mono- or bicyclic heteroaryl, wherein the aryl or heteroaryl group is optionally substituted; orHNR8bR9b, wherein R8b is —H or C1-4 alkyl, R9b is C1-6 alkyl or C3-8 cycloalkyl, either of which is optionally substituted with 1-2 groups independently selected from aryl or a 6-10 membered mono- or bicyclic heteroaryl, or R8b and R9b taken together with the nitrogen atom to which they are attached form an optionally substituted 5-8 membered partially saturated or fully saturated heterocyclic ring having up to 1 additional heteroatom selected from N, O or S. |
