Table 3. Optimization of the AgOAc-mediated (1,3)-cycloaddition on the CPG-bound oligonucleotides hexT conjugate 20a ^a .

Entry	21a [equiv.]	22a [equiv.]	Ag(i) [equiv.]	T [°C]	Solvent	Conversion b [%]
1	1000	1000	100	22	ACN	31
2	1000	1000	200	22	ACN	29
3	1000	1000	100	40	ACN	48
4	1000	1000	200	40	ACN	36
5	2000	2000	100	40	ACN	41
6	4000	4000	100	40	ACN	53
7	1000	3000	100	50	ACN	68
8	1000	4000	100	50	ACN	70
9	1000	4000	100	50	ACN/TEOF (2 : 1)	70
10 c	1000	4000	100	50	ACN/TEOF (2 : 1)	66
11 d	1000	4000	100	50	ACN/TEOF (2 : 1)	68
12 e	1000	4000	100	50	ACN/TEOF (2 : 1)	68
13	1000	4000	100	50	MeOH/TEOF (2 : 1)	43
14	1000	4000	100	50	THF/TEOF (2 : 1)	70
15	1000	4000	100	50	Toluene/TEOF (2 : 1)	59

^aCPG-bound oligonucleotide hexT-conjugate 20a (20 nmol) and aldehyde 21a (X equiv.) in 50 μL of solvent at ambient temperature for 6 h, then AgOAc (X equiv.), dissolved in 30 μL of ACN, triethylamine (X equiv.) and N,N-dimethylacrylamide 22 (X equiv.) at T overnight. Afterwards in AMA (30% aqueous ammonia/40% aqueous methylamine, 1 : 1 (vol/vol)) at ambient temperature for 4 h.

^bDetermined by analytical RP-HPLC analysis.

^cAgTFA was used instead of AgOAc.

^dAgSbF₆ was used instead of AgOAc.

^eAgOTf was used instead of AgOAc. TEOF = triethyl orthoformate.