Full Papers
4.23–4.09 (m, 4H), 4.03 (s, 3H), 3.72 (d, J=22.3 Hz, 2H), 2.16 (s,
3H), 1.29 ppm (t, J=7.0 Hz, 6H); ESI-MS(+) calculated for
[C20H26N2O6P]+ m/z 421.15, found m/z 421.20 [M+H]+.
[D6]DMSO): d=166.7, 160.4, 156.2, 149.4, 148.6, 138.8, 131.0, 125.3,
120.4, 119.6, 115.7, 112.7, 55.8, 38.4 ppm; ESI-MS(À) calculated for
[C14H13NO6P]À m/z 322.05, found m/z 322.02 [MÀH]À.
Methyl 4-(3-acetamidophenyl)-6-((diethoxyphosphoryl)methyl)-
picolinate (17i). Yield: 39% (60 mg, 0.14 mmol); H NMR (400 MHz,
4-(2-Methoxyphenyl)-6-(phosphonomethyl)picolinic acid (18d).
Yield: 67% (67 mg, 0.21 mmol). H NMR (400 MHz, CD3OD): d=8.32
1
1
CDCl3): d=8.22 (s, 1H), 8.16 (s, 1H), 7.85 (d, J=6.8 Hz, 2H), 7.68 (d,
J=7.0 Hz, 1H), 7.43–7.32 (m, 2H), 4.28–4.05 (m, 4H), 4.00 (s, 3H),
3.67 (d, J=21.9 Hz, 2H), 2.22 (s, 3H), 1.30 ppm (t, J=7.1 Hz, 6H);
ESI-MS(+) calculated for [C20H26N2O6P]+ m/z 421.15, found m/z
421.19 [M+H]+.
(s, 1H), 7.96 (s, 1H), 7.59–7.38 (m, 2H), 7.17 (d, J=8.2 Hz, 1H), 7.11
(t, J=7.4 Hz, 1H), 3.88 (s, 3H), 3.55 ppm (d, J=21.7 Hz, 2H);
13C NMR (126 MHz, [D6]DMSO): d=166.7, 156.7, 155.5, 147.9, 147.2,
131.2, 130.6, 127.7, 126.6, 123.3, 121.5, 112.5, 56.1, 38.3 ppm; ESI-
MS(À) calculated for [C14H13NO6P]À m/z 322.05, found m/z 322.04
[MÀH]À.
Methyl 4-(2-acetamidophenyl)-6-((diethoxyphosphoryl)methyl)-
picolinate (17j). Yield: 84% (136 mg, 0.32 mmol). 1H NMR
(400 MHz, CD3OD): d=8.17 (s, 1H), 7.80 (s, 1H), 7.64–7.29 (m, 4H),
4.32–4.08 (m, 4H), 4.02 (s, 3H), 3.74 (d, J=22.3 Hz, 2H), 1.99 (s,
3H), 1.31 (t, J=7.0 Hz, 6H); ESI-MS(+) calculated for [C20H26N2O6P]+
m/z 421.15, found m/z 421.21 [M+H]+.
4-(4-Hydroxyphenyl)-6-(phosphonomethyl)picolinic acid (18e).
1
Yield: 82% (16 mg, 0.06 mmol). H NMR (400 MHz, CD3OD): d=8.38
(s, 1H), 8.08 (s, 1H), 7.81 (d, J=8.2 Hz, 2H), 6.96 (d, J=8.0 Hz, 2H),
3.56 ppm (d, J=21.4 Hz, 2H); 13C NMR (126 MHz, [D6]DMSO): d=
166.7, 159.5, 155.9, 148.8, 148.7, 128.7, 127.5, 124.0, 119.4, 116.6,
38.2 ppm; ESI-MS(À) calculated for [C13H11NO6P]À m/z 308.03,
found m/z 308.02 [MÀH]À.
Methyl 4-(4-chlorophenyl)-6-((diethoxyphosphoryl)methyl)picoli-
nate (17k). Yield: 60% (91 mg, 0.23 mmol). 1H NMR (400 MHz,
CD3OD): d=8.28 (s, 1H), 7.91 (s, 1H), 7.80 (d, J=8.7 Hz, 2H), 7.55
(d, J=8.6 Hz, 2H), 4.23–4.08 (m, 5H), 4.00 (s, 3H), 3.66 (d, J=
22.2 Hz, 2H), 1.28 ppm (t, J=7.1 Hz, 6H); ESI-MS(+) calculated for
[C18H22ClNO5P]+ m/z 398.09, found m/z 398.24 [M+H]+.
4-(3-Hydroxyphenyl)-6-(phosphonomethyl)picolinic acid (18 f).
1
Yield: 82% (77 mg, 0.30 mmol). H NMR (400 MHz, CD3OD): d=8.47
(s, 1H), 8.21 (s, 1H), 7.48–7.33 (m, 2H), 7.29 (s, 1H), 7.01 (d, J=
7.4 Hz, 1H), 3.73 ppm (d, J=22.1 Hz, 2H); 13C NMR (126 MHz,
[D6]DMSO): d=166.6, 158.6, 156.2, 148.9, 148.9, 138.5, 131.0, 125.0,
120.2, 118.0, 117.0, 113.9, 38.3 ppm; ESI-MS(À) calculated for
[C13H11NO6P]À m/z 308.03, found m/z 308.05 [MÀH]À.
Methyl 4-(3-chlorophenyl)-6-((diethoxyphosphoryl)methyl)picoli-
nate (17l). Yield: 42% (63 mg, 0.16 mmol). 1H NMR (400 MHz,
CD3OD): d=8.28 (s, 1H), 7.93 (s, 1H), 7.84 (s, 1H), 7.78–7.68 (m,
1H), 7.61–7.47 (m, 2H), 4.24–4.08 (m, 4H), 4.01 (s, 3H), 3.67 (d, J=
22.0 Hz, 2H), 1.29 ppm (t, J=6.8 Hz, 6H); ESI-MS(+) calculated for
[C18H22ClNO5P]+ m/z 398.09, found m/z 398.15 [M+H]+.
4-(2-Hydroxyphenyl)-6-(phosphonomethyl)picolinic acid (18g).
1
Yield: 76% (56 mg, 0.18 mmol). H NMR (400 MHz, CD3OD): d=8.87
(s, 1H), 8.48 (s, 1H), 7.68 (d, J=6.7 Hz, 1H), 7.45 (t, J=7.1 Hz, 1H),
7.13–7.01 (m, 2H), 3.86 ppm (d, J=22.4 Hz, 2H); 13C NMR
(126 MHz, [D6]DMSO): d=166.8, 155.5, 155.3, 147.8, 147.6, 130.9,
130.5, 127.2, 124.5, 123.1, 120.2, 116.8, 38.4 ppm; ESI-MS(À) calcu-
lated for [C13H11NO6P]À m/z 308.03, found m/z 308.09 [MÀH]À.
Methyl 4-(2-chlorophenyl)-6-((diethoxyphosphoryl)methyl)picoli-
nate (17m). Yield: 71% (114 mg, 0.29 mmol). 1H NMR (400 MHz,
CD3OD): d=8.11 (s, 1H), 7.74 (s, 1H), 7.61–7.40 (m, 4H), 4.23–4.07
(m, 4H), 3.99 (s, 3H), 3.67 (d, J=22.2 Hz, 2H), 1.28 ppm (t, J=
7.1 Hz, 6H); ESI-MS(+) calculated for [C18H22ClNO5P]+ m/z 398.09,
found m/z 398.13 [M+H]+.
4-(4-Aminophenyl)-6-(phosphonomethyl)picolinic acid (18h).
1
Yield: 56% (14 mg, 0.05 mmol). H NMR (400 MHz, CD3OD): d=8.68
(s, 1H), 8.43 (s, 1H), 8.14 (d, J=8.2 Hz, 2H), 7.56 (d, J=8.2 Hz, 2H),
3.86 ppm (d, J=22.4 Hz, 2H); 13C NMR (126 MHz, [D6]DMSO): d=
166.6, 155.5, 151.1, 149.2, 148.6, 128.2, 123.1, 123.0, 118.5, 114.6,
38.0 ppm; ESI-MS(À) calculated for [C13H12N2O5P]À m/z 307.05,
found m/z 307.09 [MÀH]À.
General procedures for the synthesis of 18a–m
Compounds 17a–m were dissolved the in a solution of 6m HCl
and heated at 1008C for 24 h. Excess HCl was removed in vacuo
followed by co-evaporation with copious amounts of water and
MeOH until precipitate was observed. The precipitate was collected
by vacuum filtration and washed with cold water to afford prod-
ucts 18a–m.
4-(3-Aminophenyl)-6-(phosphonomethyl)picolinic acid (18i).
1
Yield: 96% (48 mg, 0.16 mmol). H NMR (400 MHz, CD3OD): d=8.35
(s, 1H), 8.01 (s, 1H), 7.96–7.47 (m, 4H), 3.59 ppm (d, J=21.9 Hz,
2H); 13C NMR (126 MHz, [D6]DMSO): d=166.4, 156.3, 148.9, 148.2,
138.3, 137.9, 131.1, 125.1, 123.6, 122.4, 120.3, 119.4, 38.3 ppm; ESI-
MS(À) calculated for [C13H12N2O5P]À m/z 307.05, found m/z 307.09
[MÀH]À.
4-Phenyl-6-(phosphonomethyl)picolinic acid (18a). Yield: 29%
(14 mg, 0.05 mmol). 1H NMR (400 MHz, CD3OD): d=8.65 (s, 1H),
8.39 (s, 1H), 8.14–7.57 (m, 5H), 3.82 ppm (d, J=22.3 Hz, 2H); ESI-
MS(À) calculated for [C13H11NO5P]À m/z 292.03, found m/z 292.04
[MÀH]À.
4-(2-Aminophenyl)-6-(phosphonomethyl)picolinic acid (18j).
1
yield: 60% (60 mg, 0.19 mmol). H NMR (400 MHz, CD3OD): d=8.24
(s, 1H), 7.87 (s, 1H), 7.54–7.32 (m, 2H), 7.25–7.05 (m, 2H), 3.57 ppm
(d, J=21.7 Hz, 2H); 13C NMR (126 MHz, [D6]DMSO): d=166.7, 155.8,
155.7, 148.9, 148.7, 145.9, 130.3, 127.2, 122.6, 122.1, 117.3, 116.3,
38.3 ppm; ESI-MS(À) calculated for [C13H12N2O5P]À m/z 307.05,
found m/z 307.06 [MÀH]À.
4-(4-Methoxyphenyl)-6-(phosphonomethyl)picolinic acid (18b).
1
Yield: 61% (48 mg, 0.15 mmol). H NMR (400 MHz, [D6]DMSO): d=
8.08 (s, 1H), 7.82 (s, 1H), 7.75 (d, J=8.6 Hz, 2H), 7.09 (d, J=8.5 Hz,
2H), 3.81 (s, 3H), 3.30 ppm (d, J=21.4 Hz, 2H); 13C NMR (126 MHz,
[D6]DMSO): d=166.7, 161.0, 156.2, 148.9, 148.3, 129.2, 128.7, 124.3,
119.6, 115.2, 55.8, 38.3 ppm; ESI-MS(À) calculated for [C14H13NO6P]À
m/z 322.05, found m/z 322.10 [MÀH]À.
4-(4-Chlorophenyl)-6-(phosphonomethyl)picolinic acid (18k).
1
Yield: 97% (60 mg, 0.18 mmol). H NMR (400 MHz, [D6]DMSO): d=
8.13 (s, 1H), 7.86 (s, 1H), 7.83 (d, J=8.1 Hz, 2H), 7.62 (d, J=8.1 Hz,
2H), 3.34 ppm (d, J=21.5 Hz, 2H); 13C NMR (126 MHz, [D6]DMSO):
d=166.6, 156.3, 149.1, 147.5, 136.0, 135.0, 129.8, 129.2, 125.0,
4-(3-Methoxyphenyl)-6-(phosphonomethyl)picolinic acid (18c).
1
Yield: 71% (50 mg, 0.15 mmol). H NMR (400 MHz, CD3OD): d=8.33
(s, 1H), 8.01 (s, 1H), 7.53–7.31 (m, 3H), 7.09 (d, J=7.4 Hz, 1H), 3.89
(s, 3H), 3.56 ppm (d, J=21.8 Hz, 2H); 13C NMR (126 MHz,
&
ChemMedChem 2019, 14, 1 – 13
10
ꢀ 2019 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
ÝÝ These are not the final page numbers!