Med Chem Res (2012) 21:321–324
323
completion of reaction, the mixture was quenched with
acetic acid (20%) at -0°C. Excess of the acid was neu-
tralized with saturated NaHCO3 (15 ml) and extracted
with EtOAc (20 ml). The organic layer was washed with
water (20 ml), dried over Na2SO4, and evaporated to
get N-benzyl-(5S)-pyroglutaminol 4. Yield: 4.50 g, 73%,
Spectral data were compared and found to be identical with
reported values (Peterson et al., 1984).
(KBr): 1660, 1710, 3020, and 3400 cm-1
;
1H NMR
(CDCl3): d 1.95–2.12 (2H, m, H-4), 2.34–2.45 (1H, m,
H-3), 2.52–2.63 (1H, m, H-30), 3.47–3.60(4H, m, H-5 and
CH3), 3.76–3.80 [1H, dd (J = 2.5 and 10.5 Hz, respec-
tively), CH2N], 4.16–4.21 (2H, m, CH2N and CH2Ph), 4.93
[1H, d (J = 15.5 Hz), CH12Ph], 7.20–7.60 (7H, m, ArH);
MS(m/z): 270 (M ? 1), 190, 91, 83; Analysis for
C16H19N3O; Calculated: C,71.38; H, 7.06; N, 15.61;
Found: C,71.51; H, 7.23; N, 15.86.
General procedure for the Mitsunobu reaction
of N-benzyl-(5S)-pyroglutaminol with imidazole/
substituted imidazole
Acknowledgments The authors are extremely thankful to the Uni-
versity Grants Commission for financial assistance in favor of a major
research project and to the SAIF, Central Drug Research Institute,
Lucknow for providing all the spectral data.
N-benzyl-(5S)-pyroglutaminol 4 (1.0 equivalent) was dis-
solved in dry THF (5 ml), Diethylazodicarboxylate
(DEAD) (1.4 equivalent) and triphenyl phosphine (Ph3P)
(1.4 equivalent) were added to the solution of 4 and stirred
at room temperature for 30 min. After 30 min, imidazole
or substituted imidazole (1.2 equivalent) in THF (5 ml)
was added to it, and the reaction mixture was stirred at
room temperature for 7 h. Progress of the reaction was
monitored by TLC. At the completion of the reaction, the
solvent was evaporated under vacuum, poured into water
(15 ml) and extracted twice with ethyl acetate
(2 9 20 ml2). The combined ethyl acetate layer was
washed with saturated NaCl solution (10 ml), dried over
Na2SO4, concentrated and purified by column chromatog-
raphy on silica using 20% EtOAc–hexane as eluent to
afford the pure compound 1 and 5.
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(5S)-1-benzyl-5-(1H-imidazol-1-ylmethyl)-2-
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(5S)-1-benzyl-5-(1H-2-methylimidazol-1-ylmethyl)-2-
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Yield: 675 mg (67%); [a]2D5 - 7.21 (c 0.1 CHCl3); IR
123