J. Spencer et al. / Bioorg. Med. Chem. 19 (2011) 1802–1815
1815
found: 336.1822. IR (ATR, cmÀ1): 3180 (NH); 1666 (C@O); 1607
(C@N). CHN: calcd for C19H22N5O.1.4TFAÁ0.04H2O C, 52.81; H,
4.57; N, 14.13, found: C, 52.82; H, 5.04; N, 14.47.
66.8 (C3); 64.1 (C23); 49.3 (C26); 42.9 (C27); 41.6 (C29); 37.0
(C30); 31.2 (C16). HRMS: m/z calcd for C28H29N4O2 [M+H]+:
453.2285, found: 453.2288. IR (ATR, cmÀ1): 3387 (NH); 1695 and
1658 (2 Â C@O); 1598 (C@N).
4.68. (S)-3-Benzyl-1-(2-oxo-2-(4-(pyrimidin-2-yl)piperazin-1-
yl)ethyl)-5-phenyl-1H-benzo[e][1,4]diazepin-2(3H)-one (68)
Acknowledgements
1-(2-Pyrimidyl)piperazine (54
l
L, 0.38 mmol) was added to a
The School of Science, University of Greenwich, and GRE are
thanked for a Ph.D. studentship (to RPR) and for providing a CHN
analysis apparatus. Swansea University (EPSRC Mass Spectrometry
Service Centre) are gratefully acknowledged for HRMS
measurements.
solution of 32 (0.15 g, 0.38 mmol), HATU (0.21 g, 0.38 mmol),
DMAP (0.003 g) and EDCI (0.11 g, 0.56 mmol) in DMF (5 mL). The
solution was stirred at ambient temperature for 16 h. The resulting
mixture was diluted with H2O (30 mL), and extracted with ethyl
acetate (20 mL Â 2). The combined extracts were washed succes-
sively with a 5% KHSO4 (20 mL) solution, saturated NaHCO3
(20 mL) and brine (30 mL) and dried (MgSO4), then filtered and
concentrated. The crude product was purified by flash chromatog-
raphy (10:1 DCM/acetone) to afford 68 as a white solid (44%).
1H NMR (270 MHz) CDCl3: d 8.30 (2H, d); 7.54–7.10 (14H, m);
6.52 (1H, t); 4.86 (1H); 4.53 (1H, d); 3.93–3.48 (11H, m). 13C
NMR (270 MHz) CDCl3: 170.20 (C2); 168.7 (C5); 166.2 (C24);
161.4 (C31); 157.7 (2 Â ArC); 142.6 (ArC); 139.4 (ArC); 138.9
(ArC); 131.5 (ArC); 130.2 (2 Â ArC); 129.8 (2 Â ArC); 129.5
(2 Â ArC); 129.4 (ArC); 128.1 (4 Â ArC); 126.0 (ArC); 124.2 (ArC);
121.8 (ArC); 110.5 (ArC); 64.5 (C3); 49.7 (C23); 44.9 (C26); 43.5
(C27); 43.5 (C29); 42.0 (C30); 37.8 (C16). HRMS: m/z calcd for
Supplementary data
Supplementary data associated with this article can be found, in
References and notes
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Compound 69 was made on a 0.42 mmol scale by the same
method used to obtain 68. Flash chromatography (10:1 DCM/ace-
tone). Yield: white powder; 11%.
1H NMR (270 MHz) CDCl3: d 8.17 (1H, d); 7.54–7.10 (15H); 6.60
(2H); 4.83 (1H); 4.55 (1H); 3.92 (1H, q, J= 4.8 Hz); 3.81–3.48 (10H,
m, 5 Â CH2, H16, H26–27, H29–30). 13C NMR (270 MHz) CDCl3: d
170.2 (C2); 168.7 (C5); 166.1 (C24); 158.8 (C31); 147.9 (ArC);
142.5 (ArC); 139.3 (ArC); 138.9 (ArC); 137.6 (ArC); 131.5 (ArC);
130.2 (2 Â ArC); 129.8 (2 Â ArC); 129.6 (2 Â ArC); 129.5 (ArC);
128.1 (2 Â ArC); 128.1 (2 Â ArC); 126.0 (ArC); 124.2 (ArC); 121.8
(ArC); 113.9 (ArC); 107.2 (ArC); 64.5 (C3); 49.6 (C23); 45.0 (C26);
44.9 (C27); 44.8 (C29); 41.8 (C30); 37.8 (C16). HRMS: m/z calcd
for C33H32N5O2 [M+H]+: 530.2551, found: 530.2556. IR (ATR,
cmÀ1): 1658 (C@O); 1592 and 1564 (2 Â C@N).
4.70. (S)-3-Benzyl-1-(2-oxo-2-(piperazin-1-yl)ethyl)-5-phenyl-
1H-benzo[e][1,4]diazepin-2(3H)-one (70)
Boc-70 was prepared on a 0.34 mmol scale by the same method
used to obtain 68. Thereafter the crude was stirred with in
HCl–dioxane (4 M, 10 mL) for 16 h. The solvent was removed at
reduced pressure and the residue was reconcentrated with Et2O
(10 mL Â 4). Et2O was added and the mixture was triturated then
dried to obtain a light yellow solid (71%).
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1H NMR (270 MHz) DMSO-d6ÁD2O: d 7.65–7.12 (14H, m); 4.89
(2H, m, CH2); 3.68–3.40 (10H, m, 5 Â CH2). CH (H3) peak is
concealed by H2O peak. NH peaks are not visible. 13C NMR
(270 MHz) DMSO-d6ÁD2O: 170.2 (C2); 169.2 (C5); 166.6 (C24);
142.9 (ArC); 138.9 (ArC); 137.8 (ArC); 133.1 (ArC); 131.7 (ArC);
130.6 (ArC); 130.2 (2 Â ArC); 130.0 (2 Â ArC); 129.1 (ArC); 128.9
(2 Â ArC); 128.8 (2 Â ArC); 126.9 (ArC); 125.3 (ArC); 123.1 (ArC);
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