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. Author manuscript; available in PMC: 2023 Feb 9.
Published in final edited form as: J Med Chem. 2022 May 24;65(11):7656–7681. doi: 10.1021/acs.jmedchem.1c02171

Scheme 4. Heterocyclic Analogues of the Linker Regiona.

Scheme 4.

a(a) (i) 9-BBN, THF, 66 °C, 1 h; (ii) 1-(4-iodophenyl)ethan-1-one, Pd(dppf)Cl2·CH2Cl2, KOH(aq), THF, 66 °C, 4 h, 70%; (b) NBS, TsOH, MeCN, 82 °C, 18 h, 88%; (c) tert-butyl(4-amino-4-thioxobutyl)carbamate, 2:1 DMF/EtOH, 78 °C, 4 h, 34%; (d) tert-butyl(4-amino-4-oxobutyl)carbamate, NMP, 100 °C, 6 h, 10%; (e) N-Boc-GABA, K2CO3, MeCN, rt, 18 h, 91%; (f) 4 M HCl/dioxane, DCM, rt, 2 h, 60–94%; (g) ammonium acetate, toluene, 110 °C, 5 h, 85%; (h) (i) NaH, THF, 0 °C, 0.5 h; (ii) MeI, THF, 0–25 °C, 18 h, 63%.