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. 2024 May 29;15(26):10092–10100. doi: 10.1039/d4sc01881h

Summary of test reaction conditions.

Reaction Temperature Reagent 1 Reagent 2 Noted
1i-ii 40 EDAC HOBt Two reactions at 1.0 and 1.5 eq.
1iii-iv 40 HATU, 1.5 eq. DIPEA, 3.0 eq. Two reactions, add acid v. amine first
1v-vi 40 CDI, 1.0 eq. DIPEA, 3.0 eq.a Two reactions, add acid v. amine first
1vii 40 SOCl2, 1.5 eq. DIPEA, 3.0 eq.
2i-iii 80 KOtBu, 3.0 eq. Pd catalystsb
3i-iii 80 CuI, 0.2 eq. DBU, DBU, Cs2CO3, 3.0 eq. TBAB, aliquat 336, no PTC
4i 40 EDAC HOBt Two reactions at 1.0 and 1.5 eq.
4ii-iii 40 HATU, 1.5 eq. DIPEA, 3.0 eq. Two reactions, add acid v. amine first
4iv-v 40 CDI, 1.0 eq. DIPEA, 3.0 eq.a Two reactions, add acid v. amine first
5i-v 80 Basesc, 3.0 eq. Five different bases and eq.
5vi-viii 40 EDAC HOBt Two reactions at 1.0 eq., one at 1.5 eq.
5viv 40 PPh3, 1.0 eq. DIAD, 1.2 eq.a
5x-xi 40 CDI, 1.0 eq. DIPEA, 3.0 eq.a Two reactions, add acid v. amine first
5xii-xiii 40 SOCl2 DIPEA, 3.0 eq. Two reactions at 1.0 and 1.5 eq. SOCl2
6i-xi 80 DIPEA F-, Cl-, and Br-nitropyridine DIPEA at 1, 2, 3, and 4 eq. each X-pyr
6xii-xiii 80 DBU, 3 eq. Pd catalystsb
6xiv-xvii 40 SnCl2 HCl At 1.0, 2.0, 5.0, and 10.0 eq.
6xviii-xxi 40 EDAC HOBt Two reactions at 1.0, third at 1.5 eq.
6xxii-xxiv 40 HATU, 1.5 eq. DIPEA, 3.0 eq. Two reactions, add acid v. amine first
6xxv-xxvi 40 CDI, 1.0 eq. DIPEA, 3.0 eq.a Two reactions, add acid v. amine first
6xxvii 40 SOCl2 DIPEA, 3.0 eq. Two reactions at 1.0 and 1.5 eq. SOCl2
a

Reagent added last.

b

Palladium catalysts, in order: XPhos Pd G4, tBuBrettPhos Pd G3, (dppf)PdCl2.

c

Bases, in order, DIPEA, Cs2CO3, KOtBu, DBU, DBU (1.5 eq.).

d

Abbreviations. EDAC: 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide, HOBt: N-hydroxybenzotriazole, HATU: 2-(7-aza-1H-benzotriazole-1-yl)-1,1,3,3-tetramethyluronium hexafluorophosphate, DIPEA: diisopropyl ethyl amine, DIAD: diisopropylazodicarboxylate, DBU: 1,8-diazabicyclo[5.4.0]undec-7-ene, KOtBu: potassium tert-butoxide, TBAB: tetrabutylammonium bromide, CDI: carbonyl diimidazole, SOCl2: thionyl chloride, CuI: copper(i) iodide, PPh3: triphenylphosphine, PTC: phase transfer catalyst, X-pyr: halogenated nitropyridine.