Table 2. Base Screening for Amidation to Alkene Impurity I (9).

entry	basea	activating reagent	time(h)	temperature	overall yielda,b9 + 10 (%)	selectivity ratio 9:10c
1	NMM	EDC	1	0 °C	53	31.9
2	NMM	EDC	2	r.t.	77	30.4
3	Et3N	EDC	1	0 °C	67	17.5
4	Et3N	EDC	2	r.t.	61	15.5
5	Py	EDC	2	r.t.	43	26.2
6	DMAP	EDC	2	r.t.	39	11.1
7	NMM/DMAP = 9/1	EDC	1	0 °C	85	20.5
8	NMM/DMAP = 9/1	EDC	2	r.t.	75	17.0
9	NMM/DMAP = 1/1	EDC	1	0 °C	57	15.8
10	NMM/DMAP = 1/1	EDC	2	r.t.	54	14.8
11	NMM/Py = 1/1	EDC	1	0 °C	44	18.9
12	NMM/Py = 1/1	EDC	2	r.t.	42	18.7
13	NMMb	(COCl)2	1	0 °C	84	30.8
14	Et3Nb	(COCl)2	1	0 °C	91	23.6
15	Pyb	(COCl)2	2	0 °C	70	13.4

^aReaction conditions by coupling reagent method: (i) 15 (0.50 mmol, 0.108 g), DMF (5 mL), 0 °C, EDC × HCl (0.50 mmol, 0.096 g), 0.5 h; (ii) 3 × HCl (0.5 mmol, 0.114 g), base (0.5 mmol), 0 °C for 1 h, then r.t. for 1 h. By acid chloride method: (i) 15 (0.46 mmol, 0.10 g), CH₂Cl₂, oxalyl chloride (0.92 mmol, 0.079 mL), DMF (cat.), 0 °C, 1.5 h; (ii) 3 × HCl (0.46 mmol, 0.105 g), base (0.92 mmol), THF (5 mL), 0 °C, 1 h.

^bDetermined by HPLC.