Table 1.

Optimization of the reaction conditions ^a,b for the synthesis of 1-(4-amino-2-chloropyridin-3-yl)-2-(4-fluorophenyl)ethan-1-one (17a).

Entry	2–5 Equiv.	Solvent	Temp. (°C)	Reaction Time (h)	Yield c (%)
1	2	THF	25	16	5
2	2	Et2O	25	16	20
3	2	Et2O	30	12	35
4	2	Methyl tert-butyl ether	30	12	10
5	2	Isopropyl ether	30	12	7
6	2	Toluene	30	12	Trace
7	3	Et2O	30	12	60
8	4	Et2O	30	12	74
9	5	Et2O	30	12	73

^a Reactions were performed using 0.5 mmol of 4-amino-2-chloronicotinonitrile (15) in 1.0 mL solvent under N₂ atmosphere. ^b 2 mL HCl/H₂O/EtOH (1:1:2) solvent was added for acidolysis. ^c Isolated yield.