CPC C07D 221/16 (2013.01) [C07C 13/547 (2013.01); C07D 231/54 (2013.01); C07D 249/16 (2013.01); C07D 471/04 (2013.01); C07C 2603/36 (2017.05)] | 8 Claims |
1. A process of making a compound of formula (II):
or a pharmaceutically accepted salt thereof,
wherein:
R1 and R2 are, independently for each occurrence, F, Cl, Br, I, OTf, B(OH)2, CN, NHR5, NHS(O)2R5, OR5, OS(O)2R5, SR5, —CF3, —C(O)OC1-6 alkyl, —C(O)N(C1-6 alkyl)2, —C(O)R5, S(O)2R5, NO2, —C1-6 alkyl, —C1-6 alkenyl, or 5- to 10-membered heteroaryl substituted with 1, 2, 3, 4, or 5 R6 groups, optionally wherein the alkyl and alkenyl are substituted with one or more R5 group;
R3 and R4 are, independently for each occurrence, H or —C1-6 alkyl;
R5 is selected from H, —C1-6-alkyl, —CF3; —C(O)OC1-6 alkyl, or —C(O)N(C1-6 alkyl)2;
R6 is selected from H, F, Cl, Br, I, OTf, CN, NH2, OR5, SR5, —CF3, —C(O)R5, —C(O)OC1-6 alkyl, NO2, —C1-6 alkyl;
n is 0, 1, or 2;
p is 0, 1, or 2; and
X is CH or N;
wherein the process comprises:
(A) combining a compound of formula (III):
with a compound of formula (IV):
and a non-nucleophilic base to provide the compound of formula (V):
and
(B) combining the compound of formula (V) with a carbodiimide to provide the compound of formula (II).
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