Int. J. Mol. Sci. 2020, 21, 3602
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CDCl ) δ 171.6, 169.3, 166.3, 165.9, 156.7, 144.4, 144.0, 141.3, 128.8, 128.5, 127.8, 127.7, 127.1, 126.3, 125.1,
3
121.0, 119.9, 119.7, 66.6, 52.2, 48.6, 47.3, 42.6, 41.9, 40.3, 39.3, 35.4. Maldi-tof m/z calcd for C38
H
39
N
7
O :
4
657.3, found 658.1 (M+H)+.
Methyl 2-((4-((2-((((9H-fluoren-9-yl)methoxy)carbonyl)amino)ethyl)amino)-6-((naphthalen-1-
ylmethyl)amino)-1,3,5-triazin-2-yl)amino)acetate (13c)
The 13c was synthesized using 12c (1.26 g, 2.61 mmol) in CH
Boc-deprotection stage. Further reaction was carried out using DIEA (3.64 mL, 26 mmol) and Fmoc-
OSu (1.15 g, 3.4 mmol) in CH Cl by following the general procedure D. The crude residue was
2
Cl
2
(6 mL) and TFA (12 mL) at the
2
2
purified by silica gel column chromatography CH
2
Cl2/EtOAc (2:8→1:9) to afford 13c (1.13 g, 71%) as
1
a white solid. H NMR (500 MHz, CDCl
3
) δ 8.12–7.95 (m, 1H), 7.93–7.82 (m, 1H), 7.76 (d, J = 7.4 Hz,
3H), 7.56 (d, J = 6.2 Hz, 2H), 7.52–7.44 (m, 2H), 7.44–7.33 (m, 4H), 7.29 (d, J = 8.5 Hz, 2H), 6.24–5.43 (m,
3H), 4.96 (s, 2H), 4.51–4.26 (m, 2H), 4.26–3.96 (m, 3H), 3.80–3.53 (m, 3H), 3.51–3.15 (m, 4H), 2.82 (s,
1H). 13C NMR (100 MHz, CDCl
128.2, 127.7, 127.1, 126.4, 125.8, 125.4, 125.1, 123.5, 119.9, 66.6, 52.2, 47.2, 42.7, 41.7, 40.4. Maldi-tof m/z
calcd for C34
: 603.2, found 604.0 (M+H)+.
3) δ 171.5, 169.4, 165.8, 156.7, 144.0, 141.3, 134.2, 133.8, 131.4, 128.7,
H
33
N
O
7 4
3.1.10. General Procedure E
2-((4-((2-((((9H-Fluoren-9-yl)methoxy)carbonyl)amino)ethyl)amino)-6-(dibenzylamino)-1,3,5-triazin-
2-yl)amino)acetic acid (3a)
The 13a (1 g, 1.55 mmol) was dissolved in 10 mL of 1,4-dioxane and 10 mL of 2N HCL. The
resultant mixture was heated to reflux at 101 °C for 4 h. Then the reaction mixture was evaporated to
remove 1,4-dioxane, and the resultant residue was dissolved in H
extracted from EtOAc (2 × 15 mL). The combined organic layers were washed with brine (15 mL),
dried over anhydrous Na SO , filtered, and evaporated under vacuum. The resultant sticky solid was
treated with diethyl ether (20 mL) stirred for 20 min. The resultant solid was filtered and washed
with diethyl ether (2 × 5 mL) to afford 3a (932 mg, 95%) as a white solid. 1H NMR (400 MHz, CDCl
δ 9.56 (s, 1H), 7.71 (d, J = 7.5 Hz, 2H), 7.59 (d, J = 7.2 Hz, 2H), 7.48–7.06 (m, 14H), 5.92 (s, 1H), 4.83 –
4.47 (m, 4H), 4.28 (d, J = 7.2 Hz, 2H), 4.19–3.97 (m, 3H), 3.58–3.13 (m, 4H). 13C NMR (100 MHz, CDCl
δ 174.7, 163.4, 156.7, 156.5, 155.3, 144.0, 141.3, 136.8, 136.5, 128.7, 128.6, 127.9, , 127.6, 127.5, 127.0, 125.2,
119.9, 66.7, 49.4, 49.3, 47.2, 44.8, 40.9, 40.1. Maldi-tof m/z calcd for C36 : 629.1, found 629.1.
2
O (15 mL) and EtOAc (15 mL), and
2
4
3)
3)
H
35N
7O
4
2-((4-((2-((((9H-Fluoren-9-yl)methoxy)carbonyl)amino)ethyl)amino)-6-((3,3-diphenylpropyl)amino)-
1,3,5-triazin-2-yl)amino)acetic acid (3b)
The 3b was synthesized from 13b (2.5 g, 3.8 mmol) in 25 mL of 1,4-dioxane and 25 mL of 2N
HCL by following the general procedure E to afford 3b (2.37 g, 95% ) as a white solid. 1H NMR (400
MHz, CDCl
(m, 2H), 5.55–5.10 (m, 1H), 4.42 (d, J = 6.1 Hz, 1H), 4.29 (d, J = 7.0 Hz, 1H), 4.17 (s, 2H), 4.09–3.78 (m,
2H), 3.61–2.98 (m, 6H), 2.42–2.07 (m, 2H). 13C NMR (100 MHz, CDCl
) δ 172.1, 157.4, 156.8, 154.3,
143.9, 143.8, 141.3, 141.1, 128.7, 128.6, 127.8, 127.7, 127.2, 126.6, 126.5, 126.9, 125.3, 119.9, 66.9, 48.6, 47.1,
42.5, 40.8, 40.1, 39.7, 34.8. Maldi-tof m/z calcd for C37 : 643.2, found 643.1.
3
) δ 9.14–8.50 (m, 1H), 7.97–7.65 (m, 2H), 7.66–7.46 (m, 2H), 7.48–6.94 (m, 14H), 6.63–5.75
3
H37N
7
O4
2-((4-((2-((((9H-Fluoren-9-yl)methoxy)carbonyl)amino)ethyl)amino)-6-((naphthalen-1-
ylmethyl)amino)-1,3,5-triazin-2-yl)amino)acetic acid (3c)
The 3c was synthesized from 13c (0.9 g, 1.49 mmol) in 10 mL of 1,4-dioxane and 10 mL of 2N
HCL by following the general procedure E to afford 3c (0.80 g, 91% ) as a white solid. 1H NMR (400
MHz, CDCl ) δ 8.95–8.29 (m (br), 1H), 8.07–6.97 (m, 15H), 6.75–5.94 (m (br), 2H), 4.79 (s, 2H), 4.39–
3
3.84 (m, 5H), 3.58–2.78 (m, 4H). 13C NMR (100 MHz, DMSO) δ 171.4, 171.0, 156.7, 144.4, 141.2, 133.8,
131.4, 131.1, 129.1, 128.1, 127.5, 126.9, 126.4, 126.3, 125.9, 125.8, 125.6, 124.1, 123.8, 120.6, 65.9, 47.2, 42.9,