CHEMMEDCHEM
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for C20H28BN3O4 (385.27): C 62.35, H 7.33, N 10.91; found: C 62.11, H
7.17, N 10.96.
(R)-1-{3-[2-Oxo-4-(phenylamino)pyridin-1(2H)-yl]propanamido}-3-
methylbutylboronic acid (3b): Starting from 15g (339 mg,
0.67 mmol), compound 3b (137 mg, 55%) was obtained according
to the procedure outlined for 2a. Rf =0.10 (CHCl3/MeOH 9:1).
[a]2D0 =ꢀ13.5 (c=0.2, DMSO). 1H NMR (300 MHz, [D6]DMSO): d=
0.80–0.87 (m, 6H), 1.20–1.56 (m, 3H), 2.41 (t, J=6.5 Hz, 2H), 3.14–
3.21 (m, 1H), 3.91 (t, J=6.5 Hz, 2H), 5.71 (d, J=2.3 Hz, 1H), 5.88
(dd, J=7.0, 2.3 Hz, 1H), 7.04 (t, J=7.0 Hz, 1H), 7.13 (d, J=7.0 Hz,
2H), 7.30–7.35 ppm (m, 3H). 13C NMR (75 MHz, [D6]DMSO): d=22.8,
25.4, 35.2, 37.0, 38.5, 45.2, 45.2, 94.1, 98.9, 121.5, 123.5, 129.7,
139.4, 140.6, 153.3, 162.7, 169.9 ppm. Elemental analysis calcd (%)
for C19H26BN3O4 (371.24): C 61.47, H 7.06, N 11.32; found: C 61.29, H
7.22, N 11.01.
(R)-1-{2-[4-(4-Methoxyphenylamino)-2-oxopyridin-1(2H)-yl]aceta-
mido}-3-methylbutylboronic acid (2b): Starting from 15b
(214 mg, 0.41 mmol), compound 2b (94 mg, 59%) was obtained
according to the procedure outlined for 2a. Rf =0.13 (CHCl3/MeOH
1
9:1). [a]2D0 =ꢀ6.7 (c=0.1, DMSO). H NMR (300 MHz, [D6]DMSO): d=
0.73–0.90 (m, 6H), 1.14–1.75 (m, 3H), 3.30–3–34 (m, 1H), 3.73 (s,
3H), 4.31 (s, 2H), 5.45 (d, J=1.8 Hz, 1H), 5.82 (dd, J=7.0, 2.3 Hz,
1H), 6.90–7.10 ppm (m, 5H). 13C NMR (75 MHz, [D6]DMSO): d=22.6,
22.8, 25.5, 29.5, 31.8, 45.7, 55.7, 114.9, 124.6, 133.1, 140.0, 154.6,
156.2, 162.8, 167.4, 167.7 ppm. Elemental analysis calcd (%) for
C19H26BN3O5 (387.24): C 58.93, H 6.77, N 10.85; found: C 58.77, H
6.83, N 10.66.
(R)-1-{3-[4-(3-Ethylphenylamino)-2-oxopyridin-1(2H)-yl]propana-
mido}-3-methylbutylboronic acid (3c): Starting from 15h
(187 mg, 0.35 mmol), compound 3c (98 mg, 70%) was obtained
according to the procedure outlined for 2a. Rf =0.11 (CHCl3/MeOH
9:1). [a]2D0 =ꢀ17.1 (c=0.1, DMSO). 1H NMR (300 MHz, [D6]DMSO):
d=0.79–0.89 (m, 9H), 1.13–1.29 (m, 3H), 2.39–2.44 (m, 2H), 2.57
(q, J=7.6 Hz, 2H), 2.98–3.05 (m, 1H), 3.88–4.03 (m, 2H), 5.69 (dd,
J=6.5, 1.8 Hz, 1H), 5.86 (dd, J=7.0, 2.3 Hz, 1H), 6.87–6.96 (m, 3H),
7.18–7.34 ppm (m, 2H). 13C NMR (75 MHz, [D6]DMSO): d=16.0,
22.8, 23.7, 24.1, 25.5, 28.6, 35.2, 38.1, 38.5, 93.9, 119.0, 121.1, 123.0,
129.5, 140.5, 145.4, 153.2, 153.5, 162.6, 169.8 ppm. Elemental analy-
sis calcd (%) for C21H30BN3O4 (399.29): C 63.17, H 7.57, N 10.52;
found: C 63.25; H 7.31; N 10.71.
(R)-1-{2-[4-(Benzylamino)-2-oxopyridin-1(2H)-yl]acetamido}-3-
methylbutylboronic acid (2c): Starting from 15c (372 mg,
0.74 mmol), compound 2c (187 mg, 68%) was obtained according
to the procedure outlined for 2a. Rf =0.12 (CHCl3/MeOH 9:1).
[a]2D0 =ꢀ2.7 (c=0.1, DMSO). 1H NMR (300 MHz, [D6]DMSO): d=
0.78–0.87 (m, 6H), 1.05–1.28 (m, 3H), 3.01–3.08 (m, 1H), 4.18–
4.4.26 (m, 4H), 5.51–5.54 (m, 1H), 5.55 (dd, J=7.5, 2.2 Hz, 1H),
7.07–7.35 ppm (m, 6H). 13C NMR (75 MHz, [D6]DMSO): d=22.8,
23.3, 26.1, 32.3, 45.9, 76.7, 127.3, 127.6, 128.9, 139.2, 139.4, 156.4,
162.8, 170.1, 175.3 ppm. Elemental analysis calcd (%) for
C19H26BN3O4 (371.24): C 61.47, H 7.06, N 11.32; found: C 61.73, H
7.01, N 11.44.
(R)-1-{3-[4-(4-Methoxyphenylamino)-2-oxopyridin-1(2H)-yl]propa-
namido}-3-methylbutylboronic acid (3d): Starting from 15i
(206 mg, 0.38 mmol), compound 3d (101 mg, 66%) was obtained
according to the procedure outlined for 2a. Rf =0.13 (CHCl3/MeOH
9:1). [a]2D0 =ꢀ13.3 (c=0.1, DMSO). 1H NMR (300 MHz, [D6]DMSO):
d=0.85–0.89 (m, 6H), 1.23–1.47 (m, 3H), 2.29–2.33 (m, 2H), 2.98–
3.05 (m, 1H), 3.70 (s, 3H), 4.11–4.23 (m, 2H), 5.71 (dd, J=7.0,
1.8 Hz, 1H), 5.99 (dd, J=7.0, 2.3 Hz, 1H), 6.94–7–27 ppm (m, 5H).
13C NMR (75 MHz, [D6]DMSO): d=22.7, 22.9, 26.2, 32.1, 33.5, 45.8,
56.3, 88.4, 115.3, 127.3, 134.2, 143.6, 154.7, 157.3, 162.8, 168.7,
169.2 ppm. Elemental analysis calcd (%) for C20H28BN3O5 (401.27): C
59.87; H 7.03; N 10.47; found: C 59.88, H 7.01, N 10.73.
(R)-1-{2-[2-Oxo-3-(phenylamino)pyridin-1(2H)-yl]acetamido}-3-
methylbutylboronic acid (2d): Starting from 15d (217 mg,
0.44 mmol), compound 2d (79 mg, 50%) was obtained according
to the procedure outlined for 2a. Rf =0.11 (CHCl3/MeOH 9:1).
[a]2D0 =ꢀ13.7 (c=0.1, DMSO). 1H NMR (300 MHz, [D6]DMSO): d=
0.86 (t, J=6.6 Hz, 6H), 1.28–1.72 (m, 3H), 3.39–3.44 (m, 1H), 4.57 (s,
2H), 6.27–6.33 (m, 1H), 6.97 (d, J=7.0 Hz, 1H), 7.08–7.37 ppm (m,
6H). 13C NMR (75 MHz, [D6]DMSO): d=22.7, 25.5, 32.2, 44.4, 51.8,
89.1, 111.3, 116.7, 117.9, 129.4, 134.4, 153.3, 162.1, 170.1 ppm. Ele-
mental analysis calcd (%) for C18H24BN3O4 (357.21): C 60.52, H 6.77,
N 11.76; found: C 60.44, H 6.61, N 11.88.
(R)-1-{3-[2-Oxo-4-(piperidin-1-yl)pyridin-1(2H)-yl]propanamido}-
3-methylbutylboronic acid (3e): Starting from 15j (418 mg,
0.84 mmol), compound 3e (204 mg, 69%) was obtained according
to the procedure outlined for 2a. Rf =0.11 (CHCl3/MeOH 9:1).
[a]2D0 =ꢀ3.9 (c=0.1, DMSO). 1H NMR (300 MHz, CD3OD): d=0.64–
0.89 (m, 12H), 1.15–1.31 (m, 2H), 1.39–1.59 (m, 5H), 2.30–2.44 (m,
2H), 3.11–3.17 (m, 1H), 3.82–3.97 (m, 2H), 5.41 (s, 1H), 5.96–6.01
(m, 1H), 7.26–7.30 ppm (m, 1H). 13C NMR (75 MHz, [D6]DMSO): d=
23.3, 26.0, 26.3, 26.9, 32.0, 33.7, 44.4, 45.2, 48.7, 87.2, 111.3, 134.5,
161.3, 167.4, 173.6 ppm. Elemental analysis calcd (%) for
C18H30BN3O4 (363.26): C 59.52, H 8.32, N 11.57; found: C 59.37, H
8.44, N 11.50.
(R)-1-{2-[2-Oxo-3-(piperidin-1-yl)pyridin-1(2H)-yl]acetamido}-3-
methylbutylboronic acid (2e): Starting from 15e (430 mg,
0.89 mmol), compound 2e (171 mg, 55%) was obtained according
to the procedure outlined for 2a. Rf =0.14 (CHCl3/MeOH 9:1).
[a]2D0 =ꢀ2.4 (c=0.1, DMSO). 1H NMR (300 MHz, [D6]DMSO): d=
0.75–0.85 (m, 12H), 1.13–1.25 (m, 2H), 1.30–1.70 (m, 7H), 3.10–3.17
(m, 1H), 4.17 (s, 2H), 5.43 (s, 1H), 5.93- 0.03 (m, 1H), 7.20–
7.24 ppm (m, 1H): 13C NMR (75 MHz, [D6]DMSO): d=23.2, 26.0,
26.2, 26.5, 32.1, 44.3, 48.4, 51.8, 103.4, 111.8, 134.3, 147.5, 161.0,
167.0 173.5 ppm. Elemental analysis calcd (%) for C17H28BN3O4
(349.23): C 58.47, H 8.08, N 12.03; found: C 58.33, H 8.21, N 12.00.
(R)-1-{3-[2-Oxopyridin-1(2H)-yl]propanamido}-3-methylbutylbor-
onic acid (3a): Starting from 15 f (825 mg, 1.99 mmol), compound
3a (206 mg, 37%) was obtained according to the procedure out-
lined for 2a. Rf =0.15 (CHCl3/MeOH 9:1). [a]2D0 =ꢀ6.7 (c=0.03,
(R)-1-{3-[4-(4-Methylpiperazin-1-yl)-2-oxopyridin-1(2H)-yl]propa-
namido}-3-methylbutylboronic acid (3 f): Starting from 15k
(308 mg, 0.60 mmol), compound 3 f (159 mg, 70%) was obtained
according to the procedure outlined for 2a. Rf =0.11 (CHCl3/MeOH
9:1). [a]2D0 =ꢀ7.9 (c=0.1, DMSO). 1H NMR (300 MHz, CD3OD): d=
0.85–0.93 (m, 6H), 1.27–1.51 (m, 3H), 2.33 (s, 3H), 2.52–2.54 (m,
4H), 2.59 (t, J=6.5 Hz, 2H), 2.98–3.01 (m, 1H), 3.19 (t, J=6.6 Hz,
2H), 3.36–3.38 (m, 4H), 5.70 (d, J=2.4 Hz, 1H), 6.20 (dd, J=7.9,
1.5 Hz, 1H), 7.33 ppm (d, J=7.9 Hz, 1H). 13C NMR (75 MHz,
[D6]DMSO): d=23.3, 26.1, 32.0, 35.6, 43.1, 44.7, 45.2, 50.7, 55.7,
86.8, 111.1, 134.5, 161.3, 166.9, 173.3 ppm. Elemental analysis calcd
1
DMSO). H NMR (300 MHz, CD3OD): d=0.87 (d, J=6.6 Hz, 6H), 1.30
(m, 2H), 1.42–1.56 (m, 1H), 2.65 (t, J=6.6 Hz, 2H), 3.11–3.16 (m,
1H), 4.23 (t, J=6.6 Hz, 2H), 6.31–6.36 (m, 1H), 6.52 (d, J=8.4 Hz,
1H), 7.48–7.59 ppm (m, 2H). 13C NMR (75 MHz, [D6]DMSO): d=23.3,
26.1, 32.1, 33.6, 44.3, 45.3, 111.4, 118.8, 134.1, 138.2, 161.5,
172.9 ppm. Elemental analysis calcd (%) for C13H21BN2O4 (280.13): C
55.74; H 7.56; N 10.00; found: C 55.27, H 7.63, N 10.11.
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ChemMedChem 2014, 9, 1801 – 1816 1813