Table 1.

Optimization of the parallel microscale amide coupling reactions performed in a 96‐well plate.^[a]

Entry	Coupling reagent/base (equiv./equiv.)	Stirring[c]	Temperature [°C]	Reaction time [h]	Reaction conversion [%][b]					Average conversion [%]
					13  a	13  b	13  c	13  d	13  e
1	COMU/DIPEA (1.1/1.1)	–	50	16	–	–	–	–	–	–
2	HATU/DIPEA (1.1/1.1)	–	50	16	–	–	–	–	–	–
3	EDCI/DMAP (1.1/1.1)	–	50	16	36	6	60	54	34	38
4	EDCI/DMAP (1.1/1.1)	–	r.t.	16	63	39	79	77	54	62
5	EDCI/DMAP (1.1/1.1)	–	r.t.	92	31	1	73	23	31	32
6	EDCI/DMAP (1.5/1.5)	–	r.t.	16	79	58	92	94	67	78
7	EDCI/DMAP (1.1/1.1)	+	r.t.	16	73	48	84	88	58	70
8	EDCI/DMAP (1.5/1.5)	+	r.t.	16	85	71	91	92	56	79
9[d]	EDCI/DMAP (1.5/1.5)	+	r.t.	16	80	46	93	90	61	74
10	EDCI (1.5)	+	r.t.	16	12	30	9	14	29	19
11	EDCI/HOBt (1.5/1.5)	+	r.t.	16	6	2	34	64	82	38
12	EDCI/DIPEA (1.5/3.0)	+	r.t.	16	25	27	21	11	10	19
13	DCC/DMAP (1.5/1.5)	+	r.t.	16	46	32	39	60	31	42
14[e]	EDCI/DMAP (1.5/1.5)	+	r.t.	16	88	74	93	96	55	81
15	EDCI/DMAP (1.5/1.5)	+	r.t.	3	87	72	82	85	53	76

^[a] Reaction conditions: in one well of 96‐well plate, in DMSO‐d ₆ (120 μL), 7 (3 mg, 18.6 μmol) reacted with a carboxylic acid (1 equiv.) in the presence of indicated coupling reagent and base at the indicated temperature and reaction time. ^[b] As measured by semi‐q¹H‐NMR. ^[c] Micro magnetic stirring bars implemented into each well of the well plate were used; ^[d] 1.1 equiv. of carboxylic acid was used; ^[e] The reaction was performed under an N₂ atmosphere