NJC
Paper
4
.0 Hz, CH), 4.05 (1H, td, J = 8.4, 5.4 Hz, CH), 3.60 (3H, s, 1656, 1624, 1512, 1511, 1432, 1327, 1287, 1211, 1143, 968, 915,
ꢁ1 1
COOCH
3
), 3.03–3.15 (2H, m, CH
2
), 2.92–3.03 (2H, m, CH
2
).
6
839, 721, 690 cm ; H NMR (DMSO-d , 400 MHz) 10.51 (1H, s,
Ring-opening reaction of N-acetylisatin 2a–d. Phenylalanyl NH), 8.75 (1H, d, J = 8.5 Hz, NH), 8.70 (1H, d, J = 7.6 Hz, NH),
phenylalanine methyl ester hydrochloride salt 9 was suspended 7.75–7.81 (2H, m, ArH), 7.46 (1H, d, J = 2.13 Hz, ArH), 7.21–7.28
in acetonitrile under a nitrogen atmosphere. Triethylamine was (10H, m, ArH), 4.67 (1H, td, J = 9.4, 3.7 Hz, CH), 4.56 (1H, td, J =
added as the base to neutralize the acid followed by addition of 8.4, 5.4 Hz, CH), 3.61 (3H, s, COOCH
N-acetylisatin derivatives 2a–d. The reaction mixture was stirred 2.84–3.01 (2H, m, CH ), 2.00 (3H, s, COCH
at room temperature for 10–15 minutes. Purification was con- , 101 MHz) 188.95, 171.63, 170.51, 170.28, 168.81, 162.36.63,
ducted using column chromatography using hexane and ethyl 137.38, 137.15, 136.89, 136.45, 133.29, 129.22, 129.05,
acetate as the mobile phase to give 2a–d as yellow solids. 128.29, 128.09, 126.62, 126.56, 125.16, 123.38, 114.71, 53.68,
3
), 3.01–3.07 (2H, m, CH
2
),
1
3
2
3
). C NMR (DMSO-
d
6
Methyl (2-(2-acetamidophenyl)-2-oxoacetyl)-L-phenylalanyl-L- 53.63, 51.91, 37.41, 36.65, 23.91; HR-MS (ESI): calcd for
phenylalaninate 5a: IR max 3295, 3260, 3060, 2948, 1740, 1688, C H BrN O Na: 616.1059, found 616.1042.
2
9
28
3 6
1
8
632, 1582, 1528, 1450, 1366, 1259, 1208, 1160, 1118, 990, 913,
(2-(2-Acetamidophenyl)-2-oxoacetyl)-L-phenylalanyl-L-phenyl-
ꢁ
1 1
46, 743, 696 cm ; H NMR (DMSO-d
6
, 400 MHz) 10.68 (1H, s, alanine 6a: IR max 3601, 3563, 3274, 3256, 3068, 3023, 2932,
NH), 8.95 (1H, d, J = 8.7 Hz, NH), 8.74 (1H, d, J = 7.8 Hz, NH), 1637, 1580, 1448, 1210, 1298, 1211, 1160, 983, 916, 839, 741,
ꢁ1 1
8
.14 (1H, d, J = 8.24 Hz, ArH), 7.62 (1H, td, J = 1.9, 8.7 Hz, ArH), 677 cm ; H NMR (DMSO-d
6
, 400 MHz) 12.84 (1H, bs, COOH),
7.20–7.28 (10H, m, ArH), 7.00–7.09 (2H, m, ArH), 4.79 (1H, td, 10.67 (1H, s, NH), 8.91 (1H, d, J = 8.7 Hz, NH), 8.57 (1H, d, J =
J = 10.0, 4.0 Hz, CH), 4.56 (1H, td, J = 8.4, 5.4 Hz, CH), 3.60 (3H, 8.6 Hz, NH), 8.13 (1H, d, J = 8.6 Hz, ArH), 7.59 (1H, td, J = 8.6,
s, COOCH ), 2.90–3.11 (2H, m, CH ), 2.70–2.90 (2H, m, CH ), 1.9 Hz, ArH), 7.20–7.28 (10H, m, ArH), 6.99–7.08 (2H, m, ArH),
3
2
2
1
3
2
1
1
1
.07 (3H, s, COCH3). C NMR (DMSO-d , 101 MHz) 192.47, 4.78 (1H, td, J = 10.0, 4.0 Hz, CH), 4.51 (1H, td, J = 8.4, 5.4 Hz,
6
71.71, 170.51, 168.87, 163.95, 139.63, 137.27, 136.94, 134.84, CH), 2.97–3.14 (2H, m, CH ), 2.76–2.92 (2H, m, CH ), 2.06 (3H,
2
2
1
3
32.60, 129.32, 129.08, 128.32, 128.18, 126.65, 126.50, 122.85, s, COCH
3
). C NMR (DMSO-d
6
, 101 MHz) 192.79, 171.72,
20.96, 120.62, 53.74, 53.30, 51.93, 37.65, 36.64, 24.43; HR-MS 171.55, 170.56, 169.34, 164.21, 139.97, 138.05, 137.82, 135.15,
Na: 538.1954, found 538.1942. 133.00, 129.82, 129.70, 128.60, 128.56, 126.87, 126.79, 123.34,
Methyl(2-(2-acetamido-5-fluorophenyl)-2-oxoacetyl)-L-phenyl- 121.66, 121.11, 54.22, 53.92, 51.93, 41.17, 38.28, 24.84; HR-MS
alanyl-L-phenylalaninate 5b: IR max 3259, 3048, 2948, 1751, (ESI): calcd for C29 Na: 524.1798, found 524.1785.
(2-(2-Acetamido-5-fluorophenyl)-2-oxoacetyl)-L-phenylalanyl-
12, 845, 742, 692 cm ; H NMR (DMSO-d , 400 MHz) 10.44 L-phenylalanine 6b: IR max 3598, 3560, 3172, 3243, 3118, 3027,
29 3 6
(ESI): calcd for C29H N O
29 3 6
H N O
1
9
680, 1631, 1562, 1521,1445, 1356, 1257, 1206, 1160, 1110, 978,
ꢁ1 1
6
(
1H, s, NH), 8.79 (1H, d, J = 9.0 Hz, NH), 8.72 (1H, d, J = 7.8 Hz, 2946, 2832, 1625, 1567, 1432, 1209, 1298, 1203, 1154, 974, 910,
ꢁ
1 1
6
NH), 7.87 (1H, dd, J = 9.1, 3.0 Hz, ArH), 7.48 (1H, td, J = 8.0, 3.3 825, 740, 677 cm ; H NMR (DMSO-d , 400 MHz) 12.81 (1H,
Hz, ArH), 7.20–7.30 (10H, m, ArH), 7.03 (1H, dd, J = 9.1, 3.0 Hz, bs, COOH), 10.43 (1H, s, NH), 8.76 (1H, d, J = 8.8 Hz, NH), 8.58
ArH), 4.70 (1H, td, J = 10.0, 4.0 Hz, CH), 4.56 (1H, td, J = 8.4, (1H, d, J = 7.8 Hz, NH), 7.87 (1H, dd, J = 9.1, 5 Hz, ArH), 7.48 (1H,
5
2
1
1
1
5
.4 Hz, CH), 3.61 (3H, s, COOCH
.83–2.99 (2H, m, CH ), 2.00 (3H, s, COCH
01 MHz) 189.47, 171.66, 170.36, 168.71, 162.69, 137.20, 136.92, td, J = 8.4, 5.4 Hz, CH), 3.07–3.15 (2H, m, CH ), 2.83–2.99 (2H, m,
3
), 2.99–3.11 (2H, m, CH
2
), td, J = 8.0, 3.3 Hz, ArH), 7.21–7.29 (10H, m, ArH), 7.02 (1H, dd,
1
3
2
3 6
). C NMR (DMSO-d , J = 9.1, 3.0 Hz ArH), 4.70 (1H, td, J = 10.0, 4.0 Hz, CH), 4.52 (1H,
2
13
34.85, 134.83, 129.28, 129.06, 128.30, 128.09, 126.63, 126.50, CH ), 2.00 (3H, s, COCH ). C NMR (DMSO-d , 101 MHz) 189.47,
2
3
6
24.66, 124.60, 123.74, 123.66, 121.13, 120.91, 117.43, 117.20, 172.72, 172.65, 171.46, 170.22, 168.70, 162.63, 155.89, 137.41, 137.32,
3.71, 53.59, 51.90, 37.47, 36.65, 24.83; HR-MS (ESI): calcd for 137.24, 134.83, 129.32, 129.11, 128.23, 128.18, 128.06, 127.96, 126.50,
C
29
H
28FN
3
O
6
Na: 533.1962, found 533.1950.
Methyl(2-(2-acetamido-5-methylphenyl)-2-oxoacetyl)-L-phenyl- 54.22, 53.61, 53.58, 37.52, 36.71, 23.81, 22.40; HR-MS (ESI): calcd for
alanyl-L-phenylalaninate 5c: IR max 3265, 2922, 2464, 2113, Na: 542.1703, found 542.1712.
(2-(2-Acetamido-5-methylphenyl)-2-oxoacetyl)-L-phenylalanyl-
H NMR (DMSO-d , 400 MHz) L-phenylalanine 6c: IR max 3260, 3023, 2768, 2416, 2112, 1728,
126.16, 124.73, 124.66, 123.74, 123.66 121.10, 120.88, 117.42, 117.18,
28 3 6
C H26FN O
1
9
1
7
2
920, 1729, 1635, 1591, 1526, 1444, 1305, 1222, 1208, 1175,
98, 913, 825, 751, 680 cm
0.57 (1H, s, NH), 8.93 (1H, d, J = 8.8 Hz, NH), 8.73 (1H, d, J = 1633, 1590, 1525, 1443, 1405, 1368, 1317, 1221, 1174, 1015, 837,
.7 Hz, NH), 8.00 (1H, d, J = 8.4 Hz, ArH), 7.41 (1H, dd, J = 8.4, 825, 776, 716, 698 cm ; H NMR (DMSO-d , 400 MHz) 10.54
ꢁ
1 1
;
6
ꢁ1 1
6
.1 Hz, ArH), 7.20–7.32 (10H, m, ArH), 7.11 (1H, d, J = 2.1 Hz, (1H, s, NH), 8.88 (1H, d, J = 8.6 Hz, NH), 8.54 (1H, d, J = 8.6 Hz,
ArH), 4.76 (1H, td, J = 10.0, 4.0 Hz, CH), 4.57 (1H, td, J = 8.4, 5.4 NH), 7.97 (1H, d, J = 8.5 Hz, ArH), 7.41 (1H, dd, J = 8.5, 1.8 Hz,
Hz, CH), 3.61 (3H, s, COOCH ), 3.02–3.13 (2H, m, CH ), 2.82–3.02 ArH), 7.19–7.30 (10H, m, ArH), 7.07 (1H, d, J = 2 Hz ArH), 4.74
), 2.20 (3H, s, CH Ar), 2.03 (3H, s, COCH
, 101 MHz) 192.29, 171.68, 170.58, 168.66, 163.94, 3.05–3.13 (2H, m, CH
3
2
1
3
(
(
1
1
5
2H, m, CH
DMSO-d
2
3
3
). C NMR (1H, td, J = 10.0, 4.0 Hz, CH), 4.50 (1H, td, J = 8.4, 5.4 Hz, CH),
6
2
), 2.80–3.05 (2H, m, CH
2
), 2.18 (3H, s,
1
3
37.33, 137.15, 136.95, 135.33, 132.35, 132.03, 129.25, 129.07, CH Ar), 2.03 (3H, s, COCH ). C NMR (DMSO-d , 101 MHz)
28.30, 128.11, 126.64, 126.49, 121.41, 120.88, 53.75, 53.44, 192.74, 173.12, 170.91, 170.56, 169.12, 164.36, 137.86, 137.81,
1.89, 37.50, 36.66, 24.30, 20.16; HR-MS (ESI): calcd for 137.82, 137.58, 135.56, 132.79, 132.50, 129.75, 129.60, 128.70,
3
3
6
C
30
H
31
N
3
O
6
Na: 552.2111, found 552.2105.
Methyl(2-(2-acetamido-5-bromophenyl)-2-oxoacetyl)-L-phenyl- 24.75, 20.64; HR-MS (ESI): calcd for C29
alanyl-L-phenylalaninate 5d: IR max 3227, 3038, 2933, 1741, found 538.1942.
128.55, 126.97, 126.93, 121.93, 121.36, 54.07, 53.93, 37.98, 37.16,
29 3 6
H N O Na: 538.1954,
13468 | New J. Chem., 2017, 41, 13462--13471
This journal is © The Royal Society of Chemistry and the Centre National de la Recherche Scientifique 2017