4
a 1H NMR ratio based on integration of the OCH3 resonance;b Isolated yield after column
chromatography; c reaction carried out with Pd(PPh3)4 (10 mol%); d degradation.
a]pyrimidines was prepared using the optimized reaction
conditions. The desired compounds were isolated in acceptable
yields. In entries 3 and 5 (Table 5) only the major products were
recovered.
In order to examine the scope of the direct sp3 arylation
reaction, a series of 5-substituted-[1,2,4]triazolo[1,5-
Table 5. Substrate scope for the direct C-H arylation
R1
R2
Yield (%)a
Entry
1
16, 56%
18, 48%
17, 9%
19, 8%
2
20, 63%
22, 40%
24, 43%
21, 0%
23, 8%
25, 0%
3
4
5
a Isolated yield after column chromatography
(b) Kovalevich J, Cornec A-S, Yao Y, James M, Crowe A,
Lee VM-Y, Trojanowski JQ, Smith AB, Ballatore C,
In conclusion, originating from a rapid method to
access the 7-(substituted)-5-methyl-[1,2,4]triazolo[1,5-
Brunden KR. J. Pharmacol. Exp. Ther. 2016; 357: 432–450;
(c) Cornec A-S, James MJ, Kovalevich J, Trojanowski JQ,
Lee VM-Y, Smith AB, Ballatore C, Brunden KR. Bioorg.
Med. Chem. Lett. 2015; 25: 4980–4982.
Arenas-Gonzalez A, Mendez-Delgado LA, Merino-Montiel
P, Padron JM, Montiel-Smith S, Vega-Baez JL, Meza-Reyes
S. Steroids 2016; 116: 13–19.
(a) Kokkonda S, Deng X, White KL, Coteron JM, Marco M,
de Las Heras L, White J, El Mazouni F, Tomchick DR,
Manjalanagara K, Rudra KR, Chen G, Morizzi J, Ryan E,
Kaminsky W, Leroy D, Martinez-Martinez MS, Jimenez-
Diaz MB, Bazaga SF, Angulo-Barturen I, Waterson D,
Burrows JN, Matthews D, Charman SA, Phillips MA, Rathod
PK. J. Med. Chem. 2016; 59: 5416–5431;
a]pyrimidine core, C-7 functionalization by Suzuki and
Sonogashira cross-coupling reactions was successfully carried
out. Further investigations were conducted involving a second
functionalization by palladium-catalyzed direct sp3 arylation.
5
6
A. Supplementary data
Supplementary data (experimental section and copies of spec-
tra for all of compounds) associated with this article can be
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