ACCEPTED MANUSCRIPT
Yield 94%, yellow solid, mp 121 °C. 1H NMR (CDCl3, 300 MHz) δ = 8.28 (d, 2H, J = 8.6 Hz, 2 HAr), 8.18-8.22
(m, 3H, 3 HAr), 7.96 (d, 2H, J = 8.6 Hz, 2 HAr), 7.53 (s, 1H, HAr), 7.32-7.36 (m, 2H, 2 HAr), 7.05 (d, 2H, J = 8.3
Hz, 2 HAr), 6.58 (d, 2H, J = 8.3 Hz, 2 HAr), 5.57 (s, 4H, 2 CH2), 5.25 (s, 1H, CH), 4.85-5.00 (m, 3H, H-(CH2),
4.27 (d, 1H, J = 14.9 Hz, CH2), CH2), 2.89 (s, 6H , N(CH3)2), 2.25 (s, 3H, CH3), 2.05 (s, 3H, CH3) ppm. 13C
NMR (CDCl3, 75 MHz) δ = 195.8, 166.0, 152.0, 147.1, 145.0, 140.5, 138.3, 138.1, 138.1, 127.6, 127.6, 127.6,
127.6, 127.6, 126.6, 123.3, 123.3, 123.3, 123.3, 122.9, 122.9, 122.9, 122.9, 122.9, 113.1, 113.1, 60.9, 57.9, 52.1,
52.1, 40.1, 39.4, 38.1, 21.7, 16.2 ppm. HRMS: Calcd. for C35H35N11O6 [M + H+] 706.2845 found 706.2850.
5-Acetyl-4-{4-[(1-benzyl-1H-1,2,3-triazol-4-yl)methoxy]phenyl}-1-[(1-benzyl-1H-1,2,3-triazol-4-yl)methyl]-
6-methyl-3,4-dihydropyrimidin-2(1H)-one 7d:
1
Yield 99, yellow Solid, mp 169 °C. H NMR (DMSO-d6, 300 MHz) δ = 8.26 (s, 1H, HAr), 8.00 (d, 1H, J = 3.4
Hz, 1 HAr), 7.87 (s, 1H, NH), 7.25-7.36 (m, 10H, 10 HAr), 7.10 (d, 2H, J = 8.6 Hz, 2 HAr), 6.87-6.90 (d, 2H, J =
8.6 Hz, 2 HAr), 5.60 (s, 2H, CH2), 5.55 (s, 2H, CH2), 5.14 (d, 1H, J = 3.1 Hz, CH), 5.08 (s, 2H, CH2), 4.78-5.02
(m, 2H, CH2), 2.51 (s, 3H, CH3), 2.04 (s, 3H, CH3) ppm. 13C NMR (DMSO-d6, 75 MHz) δ = 197.3, 157.8, 152.9,
148.4, 144.9, 143.5, 136.2, 136.2, 136.0, 129.3, 129.3, 129.3, 129.3, 129.3, 128.8, 128.8, 128.4, 128.4, 128.3,
128.3, 128.3, 128.3, 125.1, 123.8, 115.2, 113.5, 61.3, 60.5, 53.3, 52.9, 38,4, 31.1, 17.1 ppm. HRMS: Calcd. for
C33H32N8O3 [M + H+] 589.2670 found 589.2670.
5-Acetyl-4-{4-[(1-(4-nitrobenzyl)-1H-1,2,3-triazol-4-yl)methoxy]phenyl}-1-{[1-(4-nitrobenzyl)-1H-1,2,3-
triazol-4-yl]methyl}-6-methyl-3,4-dihydropyrimidin-2(1H)-one 8d:
Yield 99%, yellow Solid, mp 139 °C. 1H NMR (DMSO-d6, 300 MHz) δ = 8.33 (s, 1H, HAr), 8.19-8.24 (m, 4H, 4
HAr), 8.01 (d, 1H, J = 3.4 Hz, HAr), 7.99 (s, 1H, NH), 7.48-7.54 (m, 4H, 4 HAr), 7.11 (d, 2H, J = 8.6 Hz, 2 HAr),
6.88 (d, 2H, J = 8.6 Hz, 2 HAr), 5.79 (s, 2H, CH2), 5.75 (s, 2H, CH2), 5.15 (d, 1H, J = 3.1 Hz, CH), 5.10 (s, 2H,
CH2), 4.82-5.04 (m, 2H, CH2), 2.52 (s, 3H, CH3), 2.05 (s, 3H, CH3) ppm. 13C NMR (DMSO-d6, 75 MHz) δ =
196.6, 157.9, 152.8, 148.2, 147.7, 145.1, 143.8, 143.6, 136.3, 129.5, 129.5, 129.5, 129.5, 129.5, 129.5, 128.4,
128.4, 125.5, 124.4, 124.4, 124.4, 124.4, 124.4, 124.4, 115.1, 113.3, 61.6, 55.4, 53.1, 52.4, 38.2, 31.2, 17.1
HRMS: Calcd. for C33H30N10O7 [M + H+] 679.2372 found 679.2371.
General procedure for the synthesis of tri-1,2,3-triazole analogues of DHPMs 9d and 10d
A mixture of O-N-1,N-3-tri-propargylated compound 4d (1 mmol), sodium azide (5 equiv, 5 mmol, 325 mg),
alkyl halide (5 equiv), Et3N (1.5 equiv, 1.5 mmol, 0.2 mL), CuI (0.1 equiv, 0.1 mmon, 19 mg) in 10 mL of
water/acetonitrile mixture (v/v) was irradiated in the microwave oven at 100 °C for 5 min. The reaction mixture
was diluted with 25 mL of water, and extracted with ethyl acetate (3 x 25 mL). The organic layer was dried over
Na2SO4, evaporated under vacuum and the crude product was purified by column chromatography using
CH2Cl2/MeOH mixture (99:1, v/v) as eluent.
5-Acetyl-4-{4-[(1-benzyl-1H-1,2,3-triazol-4-yl)methoxy]phenyl}-1,3-bis[(1-benzyl-1H-1,2,3-triazol-4-
yl)methyl]-6-methyl-3,4-dihydropyrimidin-2(1H)-one 9d:
1
Yield 95%, yellow Solid, mp 81 °C. H NMR (DMSO-d6, 300 MHz) δ = 8.27 (s, 1H, HAr), 8.05 (s, 1H, HAr),
8.01 (s, 1H, HAr), 7.24-7.34 (m, 15H, 15 HAr), 7.11 (d, 2H, J = 8.2 Hz, 2 HAr), 6.83 (d, 2H, J = 8.2 Hz, 2 HAr),
5.61 (s, 2H, CH2), 5.57 (s, 2H, CH2), 5.55 (s, 2H, CH2), 5.25 (s, 1H, CH), 5.11 (d, 1H, J = 15.2 Hz, CH2), 5.08
(s, 2H, CH2), 4.83-4.95 (m, 2H, CH2), 3.95 (d, 1H, J = 15.2 Hz, CH2), 2.49 (s, 3H, CH3), 2.00 (s, 3H, CH3) ppm.
13C NMR (DMSO-d6, 75 MHz) δ = 196.1, 158.2, 152.8, 152.6, 147.7, 147.7, 147.1, 144.1, 143.8, 143.8, 143.8,
143.6, 133.0, 129.5, 129.5, 129.5, 129.5, 129.5, 129.3, 129.3, 129.3, 129.3, 129.0, 129.0, 125.0, 124.8, 124.4,
124.4, 124.4, 124.4, 124.4, 124.4, 115.2, 114.5, 61.5, 57.6, 55.4, 52.4, 52.4, 39.9, 39.7, 31.2, 17.3 ppm. HRMS:
Calcd. for C43H41N11O3 [M + H+] 760.3467 found 760.3469.
5-Acetyl-6-methyl-4-{4-[(1-(4-nitrobenzyl)-1H-1,2,3-triazol-4-yl)methoxy]phenyl}-1,3-bis{[1-(4-
nitrobenzyl)-1H-1,2,3-triazol-4-yl]methyl}-3,4-dihydropyrimidin-2(1H)-one 10d:
Yield 96%, yellow solid, mp 119 °C. 1H NMR (DMSO-d6, 300 MHz) δ = 8.32 (s, 1H, HAr), 8.22-8.26 (m, 6H, 6
HAr), 8.19 (s, 1H, HAr), 8.11 (s, 1H, HAr), 7.45-7.56 (m, 6H, 6 HAr), 7.12 (d, 2H, J = 7.6 Hz, 2 HAr), 6.86 (d, 2H, J
= 7.8 Hz, 2 HAr), 5.79 (s, 2H, CH2), 5.76 (s, 2H, CH2), 5.74 (s, 2H, CH2), 5.28 (s, 1H, CH), 5.14-5.20 (d, 1H, J =
15.2 Hz, CH2), 5.10 (s, 2H, CH2), 4.87-4.95 (m, 2H, CH2), 4.00 (d, 1H, J = 15.2 Hz, CH2), 2.49 (s, 3H, CH3),
2.02 (s, 3H, CH3) ppm. 13C NMR (DMSO-d6, 75 MHz) δ = 195.5, 157.7, 152.1, 147.2, 147.2, 147.2, 147.1,
144.2,
13