Synthesis, antimycobacterial activity, and acid dissociation constants of polyfunctionalized…
124.4, 117.8, 116.6, 78.7, 63.5, 60.4, 52.4, 52.0, 29.6 ppm;
Ar–H), 7.48–7.39 (m, 10H, Ar–H), 7.23–7.11 (m, 5H, Ar–
ꢀ
IR (ATR): m = 3058, 2952, 1731, 1608, 1568, 1472,
H), 6.54 (d, 2H, J = 8.8 Hz, Ar–H), 5.25 (d, 1H,
J = 10.2 Hz, 2-H), 4.16 (d, 1H, J = 9.2 Hz, 4-H), 3.85 (s,
3H, OCH3), 3.78–3.73 (m, 1H, 3-H), 3.49 (s, 3H, OCH3),
3.41 (q, 2H, J = 7.0 Hz, CH2), 1.04 (t, 3H, J = 7.0 Hz,
CH3) ppm; 13C NMR (100 MHz, CDCl3): d = 182.5
(C=O), 174.1 (C=O), 173.1 (C=O), 169.6 (C=O), 167.9
(C=O), 160.4, 157.6, 154.0, 142.6, 139.4, 134.5, 132.8,
131.1 (3 9 C), 130.5 (2 9 C), 129.5, 128.8 (2 9 C), 128.6
(2 9 C), 128.5 (2 9 C), 128.4 (2 9 C), 127.2, 126.8,
126.3, 124.5, 117.9, 116.3, 113.3 (2 9 C), 78.6, 65.5, 61.6,
1339 cm-1; MS (ESI): m/z = 705.2 ([M?H]?, 100), 707.2
([M?H]?, 35); HRMS (ESI): C39H29ClN2O7S calc.
[M?H]? 705.1462, found 705.1434.
(2R,4R)-Dimethyl 1-[4-(4-phenylphenyl)-5-(2-oxo-2H-chro-
mene-3-carbonyl)thiazol-2-yl]-5,5-diphenylpyrrolidine-2,4-
dicarboxylate (2e, C45H34N2O7S) Crystallized from
EtOAc:hexane as yellow prisms. Yield 94%; m.p.:
234–256 °C (decomp.); Rf = 0.23; 1H NMR (400 MHz,
CDCl3): d = 7.76–7.73 (m, 2H, Ar–H), 7.51–7.05 (m, 22H,
Ar–H), 5.16–5.12 (m, 1H, 2-H), 3.99 (dd, 1H, J = 8.1 Hz,
7.0 Hz, 4-H), 3.87 (s, 3H, OCH3), 3.42 (s, 3H, OCH3),
2.65–2.57 (m, 1H, 3-H), 2.51–2.44 (m, 1H, 30-H) ppm; 13C
NMR (100 MHz, CDCl3): d = 182.1 (C=O), 171.5 (C=O),
170.3 (C=O), 168.3 (C=O), 158.4, 157.8, 153.9, 142.2,
142.0, 140.1, 138.9, 134.7, 133.8, 132.6, 130.1 (2 9 C),
129.7 (2 9 C), 129.4 (2 9 C), 128.8, 128.7, 128.6
(2 9 C), 128.5 (2 9 C), 128.4 (2 9 C), 128.3, 127.5,
127.4, 127.0 (2 9 C), 126.6, 126.5 (2 9 C), 124.4, 117.9,
116.4, 78.7, 63.5, 60.5, 52.4, 52.0, 29.6 ppm; IR (ATR):
ꢀ
55.2, 52.5, 45.5, 34.2, 12.6 ppm; IR (ATR): m = 3062,
2948, 1731, 1708, 1607, 1568, 1469, 1343 cm-1; MS
(ESI): m/z = 740.2 ([M?H]?, 100); HRMS (ESI): C42-
H33N3O8S calc. [M?H]? 740.2057, found 740.2058.
(1R)-Methyl 2-[4-(4-chlorophenyl)-5-(2-oxo-2H-chromene-3-
carbonyl)thiazol-2-yl]-5-ethyl-4,6-dioxo-3,3-diphenyloc-
tahydropyrrolo[3,4-c]pyrrole-1-carboxylate (5b,
C41H30ClN3O7S) Crystallized from EtOAc:hexane as yel-
1
low prisms. Yield 87%; m.p.: 210–212 °C; Rf = 0.33; H
NMR (400 MHz, CDCl3): d = 7.65 (brs, 2H, Ar–H),
7.49–7.14 (m, 15H, Ar–H), 7.01 (d, 2H, J = 7.9 Hz, Ar–
H), 5.23 (d, 1H, J = 10.0 Hz, 2-H), 4.19 (d, 1H,
J = 9.1 Hz, 4-H), 3.82 (s, 3H, OCH3), 3.82–3.77 (m, 1H,
3-H), 3.40 (q, 2H, J = 6.7 Hz, CH2), 1.02 (t, 3H,
J = 6.7 Hz, CH3) ppm; 13C NMR (100 MHz, CDCl3):
d = 182.2 (C=O), 174.1 (C=O), 173.1 (C=O), 169.5 (C=O),
167.9 (C=O), 157.5, 156.1, 154.0, 143.3, 139.4, 135.3,
134.4, 133.4, 132.9, 130.9 (3 9 C), 130.5 (2 9 C), 129.5,
128.8 (2 9 C), 128.6 (2 9 C), 128.5, 128.4 (2 9 C), 128.0
(2 9 C), 127.1, 126.9, 124.7, 117.9, 116.5, 78.7, 65.5,
m = 3058, 2952, 1731, 1608, 1568, 1472, 1339 cm-1; MS
ꢀ
(ESI): m/z = 747.3 ([M?H]?, 100); HRMS (ESI): C45-
H34N2O7S calc. [M?H]? 747.2165, found 747.2139.
(2R,4R)-Dimethyl 1-[4-(naphthalen-2-yl)-5-(2-oxo-2H-chro-
mene-3-carbonyl)thiazol-2-yl]-5,5-diphenylpyrrolidine-2,4-
dicarboxylate (2f, C43H32N2O7S) Crystallized from
EtOAc:hexane as yellow prisms. Yield 97%; m.p.:
261–263 °C (decomp.); Rf = 0.25; 1H NMR (400 MHz,
CDCl3): d = 7.77–7.71 (m, 3H, Ar–H), 7.53–7.39 (m, 12H,
Ar–H), 7.33 (s, 1H, Ar–H), 7.24–7.17 (m, 3H, Ar–H),
6.99–6.92 (m, 2H, Ar–H), 6.69 (d, 1H, J = 8.3 Hz, Ar–H),
5.16–5.12 (m, 1H, 2-H), 4.01–3.97 (m, 1H, 4-H), 3.86 (s,
3H, OCH3), 3.41 (s, 3H, OCH3), 2.64–2.57 (m, 1H, 3-H),
2.51–2.43 (m, 1H, 30-H) ppm; 13C NMR (100 MHz,
CDCl3): d = 182.2 (C=O), 171.5 (C=O), 170.3 (C=O),
168.3 (C=O), 158.7, 157.8, 153.6, 141.7, 138.9, 134.6,
133.0, 132.4, 132.2, 132.1, 129.8, 129.7 (2 9 C), 129.5
(2 9 C), 128.8, 128.7, 128.6 (2 9 C), 128.4 (2 9 C),
127.9, 127.7 (2 9 C), 127.2, 126.9, 126.8, 126.6, 126.4,
126.2, 124.1, 117.7, 116.0, 78.6, 63.5, 60.5, 52.4, 52.0,
ꢀ
61.6, 52.6, 45.5, 34.2, 12.6 ppm; IR (ATR): m = 3062,
2923, 1728, 1702, 1606, 1568, 1450, 1336 cm-1; MS
(ESI): m/z = 744.2 ([M?H]?, 100), 746.2 ([M?H]?, 35);
HRMS (ESI): C41H30ClN3O7S calc. [M?H]? 744.1571,
found 744.1553.
(1R)-Methyl 5-cyclohexyl-2-[4-(4-methoxyphenyl)-5-(2-oxo-
2H-chromene-3-carbonyl)thiazol-2-yl]-4,6-dioxo-3,3-
diphenyloctahydropyrrolo[3,4-c]pyrrole-1-carboxylate (5c,
C46H39N3O8S) Crystallized from EtOAc:hexane as yellow
prisms. Yield 81%; m.p.: 165–167 °C (decomp.); Rf-
1
ꢀ
29.6 ppm; IR (ATR): m = 3063, 2949, 1733, 1607, 1569,
= 0.31; H NMR (400 MHz, CDCl3): d = 7.67 (brs, 2H,
1479, 1336 cm-1; MS (ESI): m/z = 721.2 ([M?H]?, 100);
HRMS (ESI): C43H32N2O7S calc. [M?H]? 721.2008,
found 721.2019.
Ar–H), 7.50–7.35 (m, 10H, Ar–H), 7.25–7.14 (m, 5H, Ar–
H), 6.55 (d, 2H, J = 8.7 Hz, Ar–H), 5.25 (d, 1H,
J = 10.2 Hz, 2-H), 4.14 (d, 1H, J = 9.4 Hz, 4-H), 3.87 (s,
3H, OCH3), 3.87–3.80 (m, 1H, N–CH), 3.77–3.72 (m, 1H,
3-H), 3.50 (s, 3H, OCH3), 2.03–1.12 (m, 10H, C6H11) ppm;
13C NMR (100 MHz, CDCl3): d = 182.5 (C=O), 174.3
(C=O), 173.3 (C=O), 169.7 (C=O), 168.0 (C=O), 160.4,
157.7, 154.0, 142.6, 139.5, 134.5, 132.8, 131.2 (3 9 C),
130.6 (2 9 C), 129.5, 128.8 (2 9 C), 128.6 (2 9 C),
128.5, 128.4 (3 9 C), 127.3, 126.9, 126.3, 124.4, 117.9,
(1R)-Methyl 5-ethyl-2-[4-(4-methoxyphenyl)-5-(2-oxo-2H-
chromene-3-carbonyl)thiazol-2-yl]-4,6-dioxo-3,3-dipheny-
loctahydropyrrolo[3,4-c]pyrrole-1-carboxylate (5a,
C42H33N3O8S) Crystallized from EtOAc:hexane as yellow
prisms. Yield 85%; m.p.: 167–169 °C (decomp.); Rf-
1
= 0.21; H NMR (400 MHz, CDCl3): d = 7.66 (brs, 2H,
123