Economical and scalable synthesis of 6-amino-2-cyanobenzothiazole

• Jacob R. Hauser,
• Hester A. Beard,
• Mary E. Bayana,
• Katherine E. Jolley,
• Stuart L. Warriner and
• Robin S. Bon

Beilstein J. Org. Chem. 2016, 12, 2019–2025, doi:10.3762/bjoc.12.189

• Laboratories, University of Leeds, Leeds LS2 9JT, UK 10.3762/bjoc.12.189 Abstract 2-Cyanobenzothiazoles (CBTs) are useful building blocks for: 1) luciferin derivatives for bioluminescent imaging; and 2) handles for bioorthogonal ligations. A particularly versatile CBT is 6-amino-2-cyanobenzothiazole (ACBT

• ), which has an amine handle for straight-forward derivatisation. Here we present an economical and scalable synthesis of ACBT based on a cyanation catalysed by 1,4-diazabicyclo[2.2.2]octane (DABCO), and discuss its advantages for scale-up over previously reported routes. Keywords: ACBT; cyanation; 2

• nanostructures in cellulo [12][13]. The precursor of D-aminoluciferin, 6-amino-2-cyanobenzothiazole (ACBT, 8), is an attractive building block for BLI probes and for handles for CBT ligations, because of the ease of derivatisation of its amino group. Like other functionalised CBTs, ACBT is available from