Regioselective N-alkylation of the 1H-indazole scaffold; ring substituent and N-alkylating reagent effects on regioisomeric distribution

• Ryan M. Alam and
• John J. Keating

Beilstein J. Org. Chem. 2021, 17, 1939–1951, doi:10.3762/bjoc.17.127

• regioselective N-alkylation (vide supra). N-Alkylation of C-7 Me, Br, or NO2 substituted indazoles, using conditions B (Cs2CO3 in DMF), showed an overall loss of N-2 regioselectivity (Table 4, entries 1–3), when compared with the corresponding regiochemical outcomes obtained under conditions A (NaH in THF

• proposal that under conditions A (NaH/THF), tight ion pair formation directs regioselective N-1 alkylation. To demonstrate the scope of our optimized N-1 regioselective N-alkylation protocol (conditions A), methyl ester-substituted indazole 9 was subjected to a series of alkylating reagents under both

• regioselective N-alkylation of the indazole scaffold would be of great value to the pharmaceutical industry. Focusing on 3-substituted indazoles, highly selective N-1 alkylations can be achieved using NaH in THF (conditions A) and Cs2CO3 in DMF (conditions B) as applied to primary and secondary alkyl

Regioselective synthesis of 7,8-dihydroimidazo[5,1-c][1,2,4]triazine-3,6(2H,4H)-dione derivatives: A new drug-like heterocyclic scaffold

• Nikolay T. Tzvetkov,
• Harald Euler and
• Christa E. Müller

Beilstein J. Org. Chem. 2012, 8, 1584–1593, doi:10.3762/bjoc.8.181

• ) (Scheme 2). According to our retrosynthetic analysis (Scheme 1), and based on an efficient protocol for the regioselective N-alkylation of hydantoins, we applied a four-step procedure for the synthesis of differently substituted 7,8-dihydroimidazo[5,1-c][1,2,4]triazine-3,6-diones 23–29 (Scheme 3). The

A novel asymmetric synthesis of cinacalcet hydrochloride

• Veera R. Arava,
• Laxminarasimhulu Gorentla and
• Pramod K. Dubey

Beilstein J. Org. Chem. 2012, 8, 1366–1373, doi:10.3762/bjoc.8.158

• )-tert-butanesulfinamide and regioselective N-alkylation of the naphthyl ethyl sulfinamide intermediate is described. Keywords: asymmetric synthesis; (R)-tert-butanesulfinamide; cinacalcet hydrochloride; naphthyl ethyl sulfinamide; regioselective N-alkylation; Introduction Cinacalcet hydrochloride

• at room temperature for 2 h to give the product in 85% yield (Scheme 6). Regioselective N-alkylation of N-tert-butanesulfinamides was difficult to achieve as S-alkylation can also be possible [26]. To our knowledge, limited procedures were reported for the regioselective N-alkylation of N-tert

• reaction progress, i.e., n-BuLi, LDA, Cs2CO3 with dppf/PdCl2, K2CO3 with Cu(I)/L-proline, NaH and TEA. All of them failed to initiate the reaction. Only LiHMDS worked well for the regioselective N-alkylation of sulfinylamide 4a in a better yield (72% isolated pure product) than the earlier reported