1H), 7.65 (d, J = 2.8 Hz, 1H), 7.53 (t, J = 8.0 Hz, 1H), 7.23 (dd, J
= 8.4, 2.8 Hz, 1H), 7.05 (d, J = 8.4 Hz, 1H), 3.88 (s, 3H). 13C
NMR (100 MHz, DMSO-d6): δ 166.0, 165.5, 155.4, 138.5, 130.4,
130.2, 129.3, 125.3, 124.8, 124.5, 121.2, 119.3, 119.0, 118.8,
52.3.
7.99 (d, J = 8.8 Hz, 1H), 7.97 (dd, J = 8.8, 2.4 Hz, 1H), 7.75 (dt,
J = 8.0, 1.2 Hz, 1H), 7.55 (t, J = 8.0 Hz, 1H), 7.43 (s, 1H), 7.42
(dd, J = 8.8, 2.0 Hz, 1H), 7.23 (d, J = 8.8 Hz, 1H), 6.97 (dt, J =
8.8, 1.2 Hz, 1H), 4.29 (s, 4H), 3.88 (s, 3H). 13C NMR (100 MHz,
DMSO-d6): δ 166.0, 165.4, 158.1, 146.9, 143.7, 143.5, 138.6,
130.2, 129.2, 128.5, 125.2, 125.2, 124.8, 123.7, 121.1 (2C),
119.1, 119.0, 118.5, 118.4, 117.6, 113.9, 64.1, 52.2. HRMS (ESI)
m/z calcd for C25H21N4O6+ ([M + H]+) 473.1456, found 473.1455.
4.1.3. Synthesis of 1,2,3-triazolylsalicylamides 8a–
x [Click reactions].
4.1.3.1. Methyl 3-[2-hydroxy-5-(4-(3-nitrophenyl)-
1H-1,2,3-triazol-1-yl)benzamido]benzoate (8a).
4.1.3.4. Methyl 3-[5-(4-(benzo[d][1,3]dioxol-5-yl)-
1H-1,2,3-triazol-1-yl)-2-
To a screw cap vial were added azide 15 (62.5 mg, 200 μmol),
alkyne 9a (40.0 mg, 272 μmol), CuI (19.5 mg, 100 μmol), and
anhydrous DMF (0.4 mL) at rt. The reaction mixture was stirred
at 80 °C for 16 h. Upon completion of the reaction, the reaction
mixture was cooled to rt. Purification by column chromatography
(40:1 CH2Cl2/MeOH) yielded 8a (65.3 mg, 71%) as an ivory
solid.
hydroxybenzamido]benzoate (8d).
To a screw cap vial were added azide 15 (68.4 mg, 219
μmol), alkyne 9d (48.0 mg, 328 μmol), CuI (20.9 mg, 110 μmol),
and anhydrous DMF (0.44 mL) at rt. The reaction mixture was
stirred at 80 °C for 15 h. Upon completion of the reaction, the
reaction mixture was cooled to rt. Purification by column
chromatography (10:1 hexanes/EtOAc → 20:1 CH2Cl2/MeOH)
yielded 8d (54.0 mg, 54%) as an ivory solid.
TLC: Rf 0.34 (40:1 CH2Cl2/MeOH (×2)). mp: 278.0−280.0 °C.
1H NMR (400 MHz, DMSO-d6): δ 11.87 (s, 1H), 10.71 (brs, 1H),
9.55 (s, 1H), 8.77 (t, J = 2.0 Hz, 1H), 8.45−8.44 (m, 2H), 8.41
(dt, J = 8.0, 1.2 Hz, 1H), 8.25 (ddd, J = 8.0, 2.0, 1.2 Hz, 1H),
8.01 (dd, J = 8.8, 2.4 Hz, 1H), 7.99 (dm, J = 8.0 Hz, 1H), 7.83 (t,
J = 8.0 Hz, 1H), 7.75 (dd, J = 8.0, 1.2 Hz, 1H), 7.55 (t, J = 8.0
Hz, 1H), 7.25 (d, J = 8.8 Hz, 1H), 3.89 (s, 3H). 13C NMR (100
MHz, DMSO-d6): δ 166.0, 165.1, 157.7, 148.4, 145.2, 138.6,
132.0, 131.3, 130.7, 130.2, 129.3, 128.5, 125.3, 125.1, 124.8,
122.7, 121.3, 121.0 (2C), 119.6, 119.6, 118.4, 52.2. HRMS (ESI)
m/z calcd for C23H18N5O6+ ([M + H]+) 460.1252, found 460.1246.
1
TLC: Rf 0.28 (20:1 CH2Cl2/MeOH). mp: 271.3−273.3 °C. H
NMR (400 MHz, DMSO-d6): δ 11.83 (s, 1H), 10.68 (s, 1H), 9.14
(s, 1H), 8.44 (t, J = 2.0 Hz, 1H), 8.40 (d, J = 2.8 Hz, 1H), 7.99
(dm, J = 8.0 Hz, 1H), 7.96 (dd, J = 8.8, 2.8 Hz, 1H), 7.75 (dt, J =
8.0, 1.2 Hz, 1H), 7.55 (t, J = 8.0 Hz, 1H), 7.49−7.46 (m, 2H),
7.23 (d, J = 8.8 Hz, 1H), 7.05 (d, J = 8.0 Hz, 1H), 6.08 (s, 2H),
3.88 (s, 3H). 13C NMR (100 MHz, DMSO-d6): δ 166.0, 165.3,
158.3, 147.8, 147.2, 147.1, 138.7, 130.2, 129.3, 128.3, 125.3,
125.1, 124.7, 124.4, 121.2, 121.0, 119.3, 119.0, 119.0, 118.6,
108.8, 105.7, 101.2, 52.2. HRMS (ESI) m/z calcd for
C24H19N4O6+ ([M + H]+) 459.1299, found 459.1295.
4.1.3.2. Methyl 3-[2-hydroxy-5-(4-(quinoxalin-6-
yl)-1H-1,2,3-triazol-1-yl)benzamido]benzoate (8b).
4.1.3.5. Methyl 3-[2-hydroxy-5-(4-
(phenylamino)methyl-1H-1,2,3-triazol-1-
yl)benzamido]benzoate (8e).
To a screw cap vial were added azide 15 (46.9 mg, 150 μmol),
alkyne 9b (34.8 mg, 225 μmol), CuI (14.6 mg, 75.1 μmol), and
anhydrous DMF (0.3 mL) at rt. The reaction mixture was stirred
at 80 °C for 15 h. Upon completion of the reaction, the reaction
mixture was cooled to rt. Purification by column chromatography
(2:1 hexanes/EtOAc → 40:1 CH2Cl2/MeOH) yielded 8b (51.8
mg, 74%) as an off-white solid.
Azide 15 (50.0 mg, 160 μmol), alkyne 9e (21.0 mg, 160 μmol)
and TBTA (4.3 mg, 5 mol%) were dissolved in 1:1 t-BuOH/H2O
(380 μL). CuSO4 (1 M solution, 3.2 μL, 2 mol%) and sodium
ascorbate (1 M solution, 16.0 μL, 10 mol%) were added and the
reaction mixture was stirred at 80 °C for 2 h. After completion of
the reaction, the mixture was concentrated, basified with
saturated aqueous NaHCO3 (3 mL), and extracted with CH2Cl2 (3
× 5 mL). The combined organic extracts were dried over
anhydrous MgSO4, filtered, and concentrated by rotary
evaporation to afford the crude product as a brown solid.
Purification by column chromatography (60:1 CH2Cl2/MeOH)
yielded 8e (45.3 mg, 64%) as a light brown solid.
1
TLC: Rf 0.21 (20:1 CH2Cl2/MeOH). mp: 270.1−272.1 °C. H
NMR (400 MHz, DMSO-d6): δ 11.87 (s, 1H), 10.71 (s, 1H), 9.59
(s, 1H), 9.00 (d, J = 1.6 Hz, 1H), 8.97 (d, J = 1.6 Hz, 1H), 8.65
(d, J = 1.6 Hz, 1H), 8.48 (dd, J = 8.0, 1.6 Hz, 1H), 8.48−8.45 (m,
2H), 8.25 (d, J = 8.4 Hz, 1H), 8.03 (dd, J = 8.8, 2.8 Hz, 1H), 8.01
(d, J = 8.8 Hz, 1H), 7.76 (d, J = 8.0 Hz, 1H), 7.56 (t, J = 8.0 Hz,
1H), 7.26 (d, J = 8.8 Hz, 1H), 3.89 (s, 3H). 13C NMR (100 MHz,
DMSO-d6): δ 166.0, 165.2, 158.1, 146.4, 146.0, 145.6, 142.6,
142.1, 138.6, 131.9, 130.2, 130.0, 129.3, 128.4, 127.6, 125.4,
125.1, 124.7, 124.5, 121.4, 121.2, 121.0, 119.5, 118.5, 52.2.
1
TLC: Rf 0.27 (20:1 CH2Cl2/MeOH). mp: 166.0−168.0 °C. H
NMR (400 MHz, DMSO-d6): δ 11.85 (brs, 1H), 10.66 (brs, 1H),
8.62 (s, 1H), 8.41 (t, J = 1.6 Hz, 1H), 8.35 (d, J = 2.8 Hz, 1H),
7.98 (dm, J = 8.0 Hz, 1H), 7.92 (dd, J = 8.8, 2.8 Hz, 1H), 7.75
(dt, J = 8.0, 1.6 Hz, 1H), 7.54 (t, J = 8.0 Hz, 1H), 7.18 (d, J = 8.8
Hz, 1H), 7.08 (dd, J = 7.6, 1.2 Hz, 2H), 6.67 (d, J = 7.6 Hz, 2H),
6.55 (t, J = 7.6 Hz, 1H), 6.13 (m, 1H), 4.37 (d, J = 4.8 Hz, 2H),
3.88 (s, 3H). 13C NMR (100 MHz, CDCl3 + CD3OD): δ 167.2,
166.7, 160.1, 147.5, 147.4, 137.8, 130.9, 129.4, 129.3, 129.1,
126.3, 126.1, 126.0, 122.3, 120.6, 120.4, 119.2, 118.4, 116.8,
+
HRMS (ESI) m/z calcd for C25H19N6O4 ([M + H]+) 467.1462,
found 467.1464.
4.1.3.3. Methyl 3-[5-(4-(2,3-
dihydrobenzo[b][1,4]dioxin-6-yl)-1H-1,2,3-triazol-
1-yl)-2-hydroxybenzamido]benzoate (8c).
To a screw cap vial were added azide 15 (62.5 mg, 200
μmol), alkyne 9c (48.1 mg, 300 μmol), CuI (19.5 mg, 100 μmol),
and anhydrous DMF (0.4 mL) at rt. The reaction mixture was
stirred at 80 °C for 16 h. Upon completion of the reaction, the
reaction mixture was cooled to rt. Purification by column
chromatography (40:1 CH2Cl2/MeOH) yielded 8c (92.5 mg,
98%) as an ivory solid.
+
113.4, 52.4, 39.8. HRMS (ESI) m/z calcd for C24H22N5O4 ([M +
H]+) 444.1666, found 444.1669.
4.1.3.6. Methyl 3-[2-hydroxy-5-(4-((5-
methylisoxazol-3-yl)amino)methyl-1H-1,2,3-triazol-
1-yl)benzamido]benzoate (8f).
1
TLC: Rf 0.18 (40:1 CH2Cl2/MeOH). mp: 246.1−247.8 °C. H
NMR (400 MHz, DMSO-d6): δ 11.84 (s, 1H), 10.69 (brs, 1H),
9.14 (s, 1H), 8.44 (t, J = 2.0 Hz, 1H), 8.41 (d, J = 2.8 Hz, 1H),
Azide 15 (68.8 mg, 220 μmol), alkyne 9f (30.0 mg, 220
μmol), CuSO4 (7.0 mg, 44.1 µmol) and sodium ascorbate (43.6
mg, 220 μmol) were dissolved in 1:1 t-BuOH/H2O (2.2 mL). The