Thieme
Original Article
added. Finally, the 5-oxo-1-phenylpyrrolidine-3-carboxylic acid (1)
(0.005mol, 1.025ml) was added to it and the reaction mixture was
refluxed for about 11h. The reaction mixture was concentrated and
kept overnight. The free base was obtained by neutralizing the cold
solution of the salt in 5mL of chloroform with 10% aq. sodium bicar-
bonate solution. The chloroform layer was extracted and dried over
Na2SO4. Concentration of the organic layer gave free base. The re-
sulting products were purified by column chromatography.
(CDCl3): δ (ppm) 7.53-7.23 (m, 5Harom), 7.36-7.17 (m, 5Harom),
4.25-4.13 (m, 1Hpyrroli), 4.07-3.92 (J=1.5Hz, d, 2Hpyrroli), 3.26-3.21
(m, 1Hpyrroli), 2.95-2.87 (m. 2Hmannich); 13C NMR (CDCl3): δ 36.56,
37.38, 53.45, 57.49, 61.70, 79.64, 123.23, 124.26, 126.67, 137.78,
170.37, 171.62 ; MS: m/z = 412, molecular formula: C25H20N2O4.
4-((2,4-dioxothiazolidin-3-yl)methyl)-5-oxo-1-
phenylpyrrolidine-3-carboxylic acid (4e)
This compound was obtained as white solid in ~ 37% yield, m.p.:89-
93°C, Rf value: 0.47 [Hexane: Ethyl acetate] (8.0:2.0v/v) as mobile
phase; IR (KBr) νmax. 2997 ( = CH stretching); 2891.5 (-CH stretch-
ing), 1729.3 (C = O stretching), 3453.7 (-OH stretching); 1313.8
(-C-N stretching); 1163.1 (-C-O stretching), 1H NMR (CDCl3): δ
(ppm) 7.53-7.23 (m, 5Harom), 4.23 (s, 2Hthiazoli ), 3.91-3.75 (m,
2Hpyrroli), 3.37-3.21 (m, 1Hpyrroli), 3.42-3.31 (m, 1Hpyrroli), 2.95-2.87
(m, 2Hmannich);13C NMR (CDCl3): δ 36.56, 37.38,53.45,57.49, 61.70,
79.64, 123.23, 124.26, 126.67, 137.78, 170.37, 171.62 ; MS:
m/z = 371. Molecular formula: C15H14N2O5S.
4-(morpholinomethyl)-5-oxo-1-phenylpyrrolidine-3-
carboxylic acid (4a)
This compound was obtained as yellow oil in ~56 % yield Rf value:
0.54 [Hexane: Ethyl acetate] (8.0:2.0v/v) as mobile phase; IR (KBr)
νmax. 2982 ( = CH stretching); 2890.5 (-CH stretching), 1723.7
(C = O stretching); 3436.4 (-OH stretching); 1302.4 (-C-N stretch-
ing); 1123.5 (-C-O stretching), 1H NMR (CDCl3): δ (ppm) 7.55-7.15
(m, 5Harom), 4.24-4.17 (m, 1Hpyrroli), 4.12-3.98 (m, 2Hpyrroli, 4Hmor),
2.97-2.79 (m, 1Hpyrroli, 4Hmor), 3.35.-3.27 ( m, 2Hmannich, 1Hpyrroli),
13C NMR (CDCl3): δ 35.56, 35.98, 50.42, 53.47, 61.70, 77.64,
120.23, 125.52, 129.42, 138.78, 171.72, 172.52 ; MS: m/z = 304,
molecular formula: C16H20N2O4.
5-oxo-1-phenyl-4-(piperazin-1-ylmethyl)pyrrolidine-
3-carboxylic acid (4f)
This compound was obtained as off white solid in ~ 42 % yield,
m.p.:48-52 °C, Rf value: 0.29 [Hexane: Ethyl acetate] (8.0:2.0 v/v)
as mobile phase; IR (KBr) νmax. 2907 (=CH stretching); 2901.5 (-CH
stretching), 1728.4 (C = O stretching); 3443.7 (-OH stretching);
1326.8 (-C-N stretching); 1203.1 (-C-O stretching), H NMR
(CDCl3): δ (ppm) 7.53-7.23 (m, 5Harom), 4.17-4.09 (m, 2Hpyrroli),
5-oxo-1-phenyl-4-(piperidin-1-ylmethyl)pyrrolidine-
3-carboxylic acid (4b)
This compound was obtained as orange solid in ~51 % yield,
m.p.:112-115°C, Rf value: 0.49 [Hexane: Ethyl acetate] (8.0:2.0v/v)
as mobile phase; IR (KBr) νmax. 2976 (=CH stretching); 2870.5 (-CH
stretching), 1724.7 (C = O stretching); 3447.4 (-OH stretching);
1
3.67-3.56 (m, 1Hpyrroli), 3.45-3.38 (m, 1Hpyrroli), 2.98.-2.81 (m,
2Hmannich), 2.79-2.65 (m, 4Hpipera), 3.01-2.97 (m, 4Hpipera)
13C NMR
1
1302.4 (-C-N stretching); 1143.5 (-C-O stretching), H NMR
(CDCl3): δ (ppm) 7.57-7.13 (m, 5Harom), 4.24-4.09 (m, 1Hpyrroli),
4.02-3.99 (m, 1Hpyrroli and 4Hpiperi), 2.97-2.79 (m, 1Hpyrroli and
4Hpiperi), 3.36-3.31 (m, 1Hpyrroli), 2.92-2.89 (m, 2Hmannich) 1.18-1.31
(m, 2Hpiperi),) 13C NMR (CDCl3): δ 34.56, 35.38, 51.42, 57.47, 63.70,
78.64, 121.23, 127.15, 129.12, 134.78, 171.37, 172.62 ; MS:
m/z = 302, molecular formula: C17H22N2O3.
(CDCl3): δ 36.56, 37.38, 53.45, 56.78, 57.49, 61.70, 79.64, 123.23,
124.26, 126.67, 137.78, 170.37, 171.62 ; m/z: 334.35.
5-oxo-1-phenyl-4-((phenylamino)methyl)pyrrolidine-
3-carboxylic acid (5a)
This compound was obtained as grey solid in ~39% yield m.p.:56-
59 °C Rf value: 0.42 [Hexane: Ethyl acetate] (7.0:3.0 v/v) as mobile
phase; IR (KBr) νmax. 3416.4 (-OH stretching); 3277 (N-H stretch-
ing); 3032 ( = CH stretching); 2857 and 2736 (-CH aliphatic); 1727
(C=O stretching); 1032 (-C-O stretching) 1H NMR (CDCl3): δ (ppm)
7.56-7.44 (m, 5Harom), 7.26-7.14 (m, 5Harom), 4.03-3.91 (J=3.6Hz,
d, 2Hpyrroli), 3.33-3.18 (J = 4.5 Hz, t, 1Hpyrroli), 2.83-2.70 (J = 3.9 Hz,
t, 1Hpyrroli), 2.98.-2.87 (m, 2Hmannich), 4.56-4.59 (s, NH ) 13C NMR
(CDCl3): δ 34.56, 39.38, 54.45, 57.78, 54.49, 67.73,
79.04,119.23,124.06, 125.07, 137.08, 171.07,173.12 ; MS:
m/z = 314. Molecular formula: C18H18N2O3.
4-((diphenylamino)methyl)-5-oxo-1-
phenylpyrrolidine-3-carboxylic acid (4c)
This compound was obtained as orange solid in ~ 47 % yield,
m.p.:103-105°C, Rf value: 0.46 [Hexane: Ethyl acetate] (8.0:2.0v/v)
as mobile phase; IR (KBr) νmax. 2986 (=CH stretching); 2871.5 (-CH
stretching), 1724.7 (C = O stretching); 3437.4 (-OH stretching);
1
1312.4 (-C-N stretching); 1153.5 (-C-O stretching), H NMR
(CDCl3): δ (ppm) 7.57-7.13 (m, 5Harom), 7.23-7.33 (m, 8Harom),
6.73-6.37 (m, 2Harom), 4.24-4.09 (m, 1Hpyrroli), 4.02-3.99 (J=0.9Hz,
d, 2Hpyrroli), 3.36-3.31 (m, 1Hpyrroli), 2.91-2.87 (m, 2Hmannich); 13
C
4-(((3-chlorophenyl)amino)methyl)-5-oxo-1-
phenylpyrrolidine-3-carboxylic acid (5b)
NMR (CDCl3 75 MHz): δ 36.56, 37.38,53.45,57.49, 61.70,
79.64,123.23, 124.26, 126.67, 137.78, 170.37, 171.62 ; MS:
m/z = 386, molecular formula: C24H22N2O3.
This compound was obtained as black solid in ~35% yield m.p.:41-
43 °C Rf value: 0.48 [Hexane: Ethyl acetate] (7.0:3.0 v/v) as mobile
phase; IR (KBr) νmax. 3456.4 (-OH stretching); 3247 (N-H stretch-
ing); 2902 ( = CH stretching); 2867 and 2726 (-CH aliphatic); 1723
(C=O stretching); 1032 (-C-O stretching); 683 (C-Cl stretching) 1H
5-oxo-4-((9-oxoacridin-10(9H)-yl)methyl)-1-
phenylpyrrolidine-3-carboxylic acid (4d)
This compound was obtained as green solid in ~ 57 % yield,
m.p.:136-140°C, Rf value: 0.37 [Hexane: Ethyl acetate] (8.0:2.0v/v)
as mobile phase; IR (KBr) νmax. 2976 (=CH stretching); 2867.5 (-CH
stretching), 1726.7 (C = O stretching); 3436.4 (-OH stretching);
NMR (CDCl3): δ (ppm) 7.54-7.47 (m, 5Harom), 7.34-7.27 (m, 2Harom
)
4.03-3.99 (J=1.2Hz, d, 2Hpyrroli), 3.81-3.65 (m, 1Hpyrroli), 3.29-3.01
(m, 1Hpyrroli), 4.97-4.81 (s, NH), 2.97-2.81 (J =4.5 Hz, d, 2Hmannich),
13C NMR (CDCl3): δ 32.56, 42.38, 44.45, 47.78, 54.49, 63.73,
1
1323.4 (-C-N stretching); 1143.5 (-C-O stretching), H NMR
Devi P et al. Pyrrolidine-3-Carboxylic Acid Analogs … Drug Res