PAPER
Dipeptidyl Benzoxaboroles and Their Peptidomimetics
2851
1H NMR (400 MHz, DMSO-d6): δ = 10.36 (s, 1 H), 9.25 (s, 1 H),
8.36 (d, J = 8.8 Hz, 1 H), 8.02 (s, 1 H), 7.63 (d, J = 8.3 Hz, 1 H),
7.41 (d, J = 7.4 Hz, 2 H), 7.36 (d, J = 8.3 Hz, 1 H), 7.34–7.28 (m, 3
H), 7.27 (d, J = 1.0 Hz, 1 H), 7.21 (dd, J = 7.3 Hz, 1 H), 7.06 (d,
J = 8.1 Hz, 1 H), 6.12 (s, 2 H), 4.95 (s, 2 H), 4.55 (m, 1 H), 3.18 (dd,
J = 13.5, 4.1 Hz, 1 H), 3.01 (dd, J = 13.2, 10.5 Hz, 1 H).
13C NMR (101 MHz, DMSO-d6): δ = 170.2, 162.9, 157.7, 149.4,
149.1, 148.0, 137.7, 137.5, 129.3, 128.2, 126.5, 122.6, 121.6, 121.4,
120.0, 117.9, 109.0, 105.2, 101.9, 69.7, 58.8, 37.8.
was purified by flash chromatography (PE–EtOAc, 1:1 to 1:2) to
give 4g (68.2 mg, 45%) as a white solid; mp 155–157 °C.
[α]D25 +3.8 (c 0.05, MeOH).
IR (KBr): 3435, 3117, 3064, 3024, 2971, 2932, 2873, 1689, 1618,
1542, 1507, 1482, 1429, 1400, 1365, 1300, 1232, 1081, 1051, 979,
831, 757, 731, 701 cm–1.
1H NMR (400 MHz, DMSO-d6): δ = 10.34 (s, 1 H), 9.21 (s, 1 H),
8.53 (d, J = 8.6 Hz, 1 H), 8.10 (d, J = 8.6 Hz, 2 H), 8.08–8.03 (m, 2
H), 7.87–7.83 (m, 1 H), 7.71–7.67 (m, 1 H), 7.63 (dd, J = 8.3, 1.8
Hz, 1 H), 7.41 (d, J = 7.5 Hz, 2 H), 7.36 (d, J = 8.3 Hz, 1 H), 7.27
(dd, J = 7.6 Hz, 2 H), 7.15 (dd, J = 7.4 Hz, 1 H), 5.17 (dd, J = 10.2,
5.5 Hz, 1 H), 4.95 (s, 2 H), 3.45 (dd, J = 14.5, 5.4 Hz, 1 H), 3.28 (dd,
J = 14.5, 10.3 Hz, 1 H), 3.20 (s, 3 H).
13C NMR (101 MHz, DMSO-d6): δ = 168.0, 165.2, 158.3, 149.3,
147.1, 143.2, 137.6, 137.4, 137.3, 130.7, 129.1, 129.0, 128.4, 128.2,
127.9, 127.8, 126.6, 123.0, 121.9, 121.6, 118.7, 69.7, 62.5, 34.3,
32.6.
HRMS-ESI: m/z [M + CH3OH – H2O + H]+ calcd for C26H24BN4O6:
499.1789; found: 499.1808.
(S)-N-(1-Hydroxy-1,3-dihydro-2,1-benzoxaborol-6-yl)-2-
{methyl[5-(pyrazin-2-yl)-1,3,4-oxadiazol-2-yl]amino}-3-phen-
ylpropanamide (4a)
The reaction was performed according to general procedure A using
16a (111.8 mg, 0.34 mmol), NMM (41 μL, 0.37 mmol), IBCF (44
μL, 0.34 mmol), and 6 (50.9 mg, 0.34 mmol). The crude product
was purified by flash chromatography (PE–EtOAc, 1:1 to 0:1) to
give 4a (62.1 mg, 40%) as an off-white solid; mp 127–129 °C.
HRMS-ESI: m/z [M + CH3OH – H2O + H]+ calcd for C29H27BN5O4:
520.2156; found: 520.2153.
[α]D25 +10.0 (c 0.05, MeOH).
(S)-N-(1-Hydroxy-1,3-dihydro-2,1-benzoxaborol-6-yl)-2-
[methyl(5-phenyl-1,3,4-oxadiazol-2-yl)amino]-3-phenyl-
propanamide (4h)
The reaction was performed according to general procedure A using
16h (111.3 mg, 0.34 mmol), NMM (41 μL, 0.37 mmol), IBCF (44
μL, 0.34 mmol), and 6 (51.6 mg, 0.35 mmol). The crude product
was purified by flash chromatography (PE–EtOAc, 1:1 to 1:2) to
give 4h (69.7 mg, 45%) as a white solid; mp 112–114 °C.
IR (KBr): 3424, 3120, 3061, 3033, 2971, 2932, 2873, 1690, 1618,
1539, 1481, 1440, 1399, 1366, 1300, 1230, 1165, 1101, 1051, 984,
753, 732, 700 cm–1.
1H NMR (400 MHz, DMSO-d6): δ = 10.33 (s, 1 H), 9.23 (s, 1 H),
9.19 (d, J = 0.9 Hz, 1 H), 8.76 (s, 2 H), 8.04 (s, 1 H), 7.62 (dd,
J = 8.2, 1.4 Hz, 1 H), 7.38 (dd, J = 7.5 Hz, 3 H), 7.27 (dd, J = 7.5
Hz, 2 H), 7.16 (dd, J = 7.3 Hz, 1 H), 5.15 (dd, J = 10.2, 5.3 Hz, 1
H), 4.95 (s, 2 H), 3.42 (dd, J = 14.3, 5.1 Hz, 1 H), 3.26 (dd, J = 13.9,
10.9 Hz, 1 H), 3.18 (s, 3 H).
13C NMR (101 MHz, DMSO-d6): δ = 168.0, 165.1, 156.1, 149.3,
145.6, 144.7, 142.4, 139.3, 137.3, 137.2, 128.9, 128.3, 126.6, 123.0,
121.9, 121.6, 69.7, 62.5, 34.3, 32.5.
HRMS-ESI: m/z [M + CH3OH – H2O + Na]+ calcd for
C24H23BN6NaO4: 493.1772; found: 493.1780.
[α]D25 +4.0 (c 0.05, MeOH).
IR (KBr): 3389, 3319, 3117, 3061, 3030, 2970, 2929, 2870, 1690,
1625, 1587, 1552, 1538, 1486, 1447, 1400, 1365, 1299, 1231, 1056,
984, 730, 693 cm–1.
1H NMR (400 MHz, DMSO-d6): δ = 10.30 (s, 1 H), 9.24 (s, 1 H),
8.05 (s, 1 H), 7.83 (d, J = 4.1 Hz, 2 H), 7.61 (d, J = 8.2 Hz, 1 H),
7.57–7.48 (m, 3 H), 7.37 (dd, J = 7.6 Hz, 3 H), 7.26 (dd, J = 7.4 Hz,
2 H), 7.15 (dd, J = 7.3 Hz, 1 H), 5.09 (dd, J = 10.0, 5.3 Hz, 1 H),
4.95 (s, 2 H), 3.40 (dd, J = 14.4, 5.1 Hz, 1 H), 3.23 (dd, J = 13.7,
10.7 Hz, 1 H), 3.14 (s, 3 H).
(S)-N-(1-Hydroxy-1,3-dihydro-2,1-benzoxaborol-6-yl)-2-
{methyl[5-(1-methyl-1H-indol-2-yl)-1,3,4-oxadiazol-2-yl]ami-
no}-3-phenylpropanamide (4f)
13C NMR (101 MHz, DMSO-d6): δ = 168.2, 164.2, 158.0, 149.2,
137.4, 137.2, 130.6, 129.1, 128.9, 128.3, 126.5, 125.2, 124.0, 123.0,
121.8, 121.6, 69.7, 62.4, 34.2, 32.3.
HRMS-ESI: m/z [M + CH3OH – H2O + H]+ calcd for C26H26BN4O4:
469.2047; found: 469.2047.
The reaction was performed according to general procedure A using
16f (165.1 mg, 0.44 mmol), NMM (53 μL, 0.48 mmol), IBCF (57
μL, 0.44 mmol), and 6 (64.2 mg, 0.43 mmol). The crude product
was purified by flash chromatography (PE–EtOAc, 1:1 to 0:1) to
give 4f (90.9 mg, 42%) as a white solid; mp 158–160 °C.
[α]D25 +5.8 (c 0.05, MeOH).
(S)-2-{[5-(1,3-Benzodioxol-5-yl)-1,3,4-oxadiazol-2-yl](meth-
yl)amino}-N-(1-hydroxy-1,3-dihydro-2,1-benzoxaborol-6-yl)-3-
phenylpropanamide (4i)
The reaction was performed according to general procedure A using
16i (67.3 mg, 0.18 mmol), NMM (22 μL, 0.20 mmol), IBCF (24 μL,
0.19 mmol), and 6 (27.5 mg, 0.18 mmol). The crude product was
purified by flash chromatography (PE–EtOAc, 1:1 to 1:3) to give 4i
(30.0 mg, 33%) as a white solid; mp 155–156 °C.
IR (KBr): 3392, 3304, 3190, 3128, 3058, 3029, 2935, 2876, 1690,
1669, 1633, 1590, 1548, 1516, 1479, 1459, 1397, 1365, 1300, 1232,
1147, 1052, 983, 733, 698 cm–1.
1H NMR (400 MHz, DMSO-d6): δ = 10.29 (s, 1 H), 9.21 (s, 1 H),
8.05 (s, 1 H), 7.66 (d, J = 7.8 Hz, 1 H), 7.62 (d, J = 8.2 Hz, 1 H),
7.55 (d, J = 8.1 Hz, 1 H), 7.43–7.33 (m, 3 H), 7.33–7.23 (m, 3 H),
7.20–7.09 (m, 2 H), 7.06 (s, 1 H), 5.14–5.03 (m, 1 H), 4.94 (s, 2 H),
4.05 (s, 3 H), 3.47–3.37 (m, 1 H), 3.29–3.20 (m, 1 H), 3.16 (s, 3 H).
13C NMR (101 MHz, DMSO-d6): δ = 168.1, 163.5, 153.3, 149.3,
138.7, 137.4, 137.2, 128.9, 128.3, 126.5, 126.4, 123.6, 123.4, 123.0,
121.9, 121.5, 121.2, 120.3, 110.4, 104.0, 69.7, 62.5, 34.2, 32.5,
31.8.
[α]D25 –14.0 (c 0.05, MeOH).
IR (KBr): 3419, 3114, 3066, 3027, 2965, 2927, 1690, 1624, 1568,
1538, 1486, 1457, 1400, 1364, 1297, 1260, 1235, 1036, 731, 700
cm–1.
1H NMR (400 MHz, CDCl3): δ = 9.18 (s, 1 H), 7.80 (s, 1 H), 7.78
(s, 1 H), 7.39–7.12 (m, 8 H), 6.83 (d, J = 7.8 Hz, 1 H), 6.02 (s, 2 H),
5.12–4.92 (m, 3 H), 3.46 (dd, J = 14.2, 6.8 Hz, 1 H), 3.22 (s, 3 H),
3.25–3.13 (m, 1 H).
13C NMR (101 MHz, CDCl3): δ = 167.4, 164.2, 159.1, 150.0, 148.2,
136.7, 136.3, 128.9, 128.8, 127.0, 123.4, 121.8, 121.5, 120.7, 117.8,
108.7, 106.1, 101.7, 71.0, 62.7, 34.4, 32.0.
HRMS-ESI: m/z [M + CH3OH – H2O + H]+ calcd for C29H29BN5O4:
522.2313; found: 522.2308.
(S)-N-(1-Methoxy-1,3-dihydro-2,1-benzoxaborol-6-yl)-2-
{methyl[5-(quinolin-2-yl)-1,3,4-oxadiazol-2-yl]amino}-3-phen-
ylpropanamide (4g)
The reaction was performed according to general procedure A using
16g (112.7 mg, 0.30 mmol), NMM (36 μL, 0.33 mmol), IBCF (39
μL, 0.30 mmol), and 6 (44.6 mg, 0.30 mmol). The crude product
© Georg Thieme Verlag Stuttgart · New York
Synthesis 2013, 45, 2843–2852