R. Wang et al.
MED
7.48–7.21 (m, 17H), 7.11 (t, J=7.2 Hz, 1H), 7.04 (s, 1H), 6.19 (s, 1H),
5.44 (s, 2H), 2.32 ppm (s, 3H); 13C NMR (100 MHz, [D6]DMSO): d=
164.8, 164.4, 152.9, 141.9, 141.2, 139.6, 138.5, 136.2, 136.0, 133.3,
131.8, 130.8, 128.9, 128.7, 128.5, 127.8, 127.5, 127.0, 126.8, 126.6,
125.8, 124.2, 123.8, 121.5, 119.8, 118.9, 113.8, 112.6, 111.3, 110.2,
55.6, 49.5, 21.3 ppm; MS (MALDI): m/z (%): 691 [M+H]+ (100%),
713 [M+Na]+ (14%), 729 [M+K]+ (6%); HRMS (MALDI): m/z calcd
for C42H32ClN4O2S [M+H]+: 691.1929, found: 691.1937; HPLC (meth-
od B): tR =14.72 min (80.2%).
127.8, 127.5, 127.0, 126.6, 124.1, 123.7, 122.2, 121.5, 119.8, 118.9,
114.3, 112.8, 111.3, 110.3, 55.4, 49.5, 30.4, 21.3, 20.8 ppm; MS (ESI):
m/z (%): 715 [M+H]+ (100%), 737 [M+Na]+ (50%), 753 [M+K]+
(19%); HRMS (MALDI): m/z calcd for C44H35N4O4S [M+H]+:
715.2374, found: 715.2369; HPLC (method A): tR =23.15 min
(94.0%).
(Z)-4-(2-((1-(Biphenyl-4-ylmethyl)indol-3-yl)methylene)-7-methyl-
3-oxo-6-(phenylcarbamoyl)thiazolo[3,2-a]pyrimidin-5-yl)-1,2-
phenylene diacetate (BCL-LZH-39): General procedure A afforded
BCL-LZH-39 as a yellow solid (63 mg, 25%). 1H NMR (300 MHz,
CDCl3): d=9.10 (s, 0.1H), 8.11 (s, 0.9H), 7.80 (d, J=7.8 Hz, 1H), 7.57–
7.06 (m, 22H), 6.18 (s, 1H), 5.43 (s, 1.8H), 5.37 (s, 0.2H), 2.27 ppm (s,
9H); 13C NMR (100 MHz, [D6]DMSO): d=168.0, 167.9, 164.9, 164.4,
152.9, 142.1, 142.0, 141.4, 139.6, 138.6, 138.3, 136.2, 136.1, 131.8,
128.9, 128.6, 127.8, 127.5, 127.0, 126.6, 125.1, 124.3, 124.1, 123.7,
123.4, 121.9, 121.5, 120.0, 118.9, 113.8, 112.7, 111.3, 110.3, 55.1, 49.5,
21.3, 20.3 ppm; MS (ESI): m/z (%): 773 [M+H]+ (36%), 795
[M+Na]+ (100%), 811 [M+K]+ (20%); HRMS (MALDI): m/z calcd for
C46H37N4O6S [M+H]+: 773.2428, found: 773.2435; HPLC (method B):
tR =13.82 min (94.3%).
(Z)-2-((1-(Biphenyl-4-ylmethyl)indol-3-yl)methylene)-5-(4-bromo-
phenyl)-7-methyl-3-oxo-N-phenyl-thiazolo[3,2-a]pyrimidine-6-
carboxamide (BCL-LZH-35): General procedure A afforded BCL-
LZH-35 as
a
yellow solid (71 mg, 29%). 1H NMR (300 MHz,
[D6]DMSO): d=10.05 (s, 1H), 8.18 (s, 1H), 8.05 (s, 1H), 7.91 (d, J=
7.8 Hz, 1H), 7.64–7.55 (m, 9H), 7.46–7.18 (m, 11H), 7.06 (t, J=7.5 Hz,
1H), 6.22 (s, 1H), 5.66 (s, 2H), 2.13–2.08 ppm (m, 3H); 13C NMR
(100 MHz, [D6]DMSO): d=165.3, 164.8, 153.3, 141.4, 140.0, 139.5,
139.0, 136.7, 132.2, 129.6, 129.3, 129.1, 128.2, 127.9, 127.4, 127.0,
123.8, 122.0, 120.2, 119.2, 114.4, 113.1, 110.6, 56.0, 49.9, 21.7 ppm;
MS (MALDI): m/z (%): 735 [M+H]+ (100%); HRMS (MALDI): m/z
calcd for C42H32BrN4O2S [M+H]+: 735.1424, found: 735.1417; HPLC
(method A): tR =15.04 min (90.0%).
(Z)-Ethyl 2-((1-(biphenyl-4-ylmethyl)indol-3-yl) methylene)-7-
methyl-3-oxo-5-phenylthiazolo[3,2-a]pyrimidine-6-carboxylate
(BCL-LZH-40): General procedure A afforded BCL-LZH-40 as a
yellow solid (59 mg, 30%). 1H NMR (300 MHz, CDCl3): d=8.08 (s,
1H), 7.78–7.75 (m, 1H), 7.56–7.15 (m, 18H), 6.19–6.16 (m, 1H), 5.44–
5.38 (m, 2H), 4.10 (q, J=7.2 Hz, 2H), 2.52 (s, 3H), 1.19 ppm (t, J=
7.2 Hz, 3H); 13C NMR (100 MHz, CDCl3): d=165.6, 165.2, 156.5,
152.7, 141.2, 140.4, 140.2, 136.5, 134.5, 130.2, 128.8, 128.7, 128.5,
127.9, 127.8, 127.7, 127.5, 127.4, 127.1, 127.0, 126.9, 125.1, 123.8,
121.8, 118.9, 114.0, 111.5, 110.5, 108.4, 60.3, 55.3, 50.6, 22.8,
14.0 ppm; MS (ESI): m/z (%): 610 [M+H]+ (100%), 632 [M+Na]+
(5%); HRMS (MALDI): m/z calcd for C38H32N3O3S [M+H]+: 610.2159,
found: 610.2161; HPLC (method A): tR =25.48 min (80.5%).
(Z)-2-((1-(Biphenyl-4-ylmethyl)indol-3-yl)methylene)-5-(4-ethyl-
phenyl)-7-methyl-3-oxo-N-phenyl-thiazolo[3,2-a]pyrimidine-6-
carboxamide (BCL-LZH-36): General procedure A afforded BCL-
1
LZH-36 as a yellow solid (115 mg, 51%). H NMR (300 MHz, CDCl3):
d=8.10 (s, 1H), 7.78 (d, J=6.9 Hz, 1H), 7.56 (d, J=7.8 Hz, 4H),
7.46–7.17 (m, 17H), 7.08 (t, J=6.3 Hz, 1H), 6.97 (s, 1H), 6.13 (s, 1H),
5.43 (s, 2H), 2.62 (q, J=7.5 Hz, 2H), 2.33 (s, 3H), 1.20 ppm (t, J=
7.8 Hz, 3H); 13C NMR (100 MHz, [D6]DMSO): d=165.1, 164.4, 152.8,
143.9, 140.8, 139.6, 138.7, 137.2, 136.2, 136.0, 131.6, 128.9, 128.6,
128.2, 127.8, 127.0, 126.8, 126.6, 123.9, 123.6, 123.4, 121.5, 119.7,
118.8, 114.6, 113.0, 111.3, 110.2, 55.7, 49.4, 27.8, 21.2, 21.0,
15.3 ppm; MS (MALDI): m/z (%): 685 [M+H]+ (100%), 707 [M+Na]+
(12%); HRMS (MALDI): m/z calcd for C44H37N4O2S [M+H]+:
685.2632, found: 685.2623; HPLC (method A): tR =14.85 min
(75.4%).
(Z)-Ethyl 2-((1-(biphenyl-4-ylmethyl)indol-3-yl)methylene)-5-(4-
fluorophenyl)-7-methyl-3-oxo-thiazolo[3,2-a]pyramidine-6-car-
boxylate (BCL-LZH-41): General procedure A afforded BCL-LZH-41
1
as a yellow solid (141 mg, 68%). H NMR (300 MHz, CDCl3): d=8.12
(Z)-3-(2-((1-(Biphenyl-4-ylmethyl)indol-3-yl)methylene)-7-methyl-
3-oxo-6-(phenylcarbamoyl)thiazolo[3,2-a]pyrimidin-5-yl)phenyl
acetate (BCL-LZH-37): General procedure A afforded BCL-LZH-37
(s, 0.8H), 7.80 (dd, J=7.5, 1.8 Hz, 0.8H), 7.67 (s, 0.2H), 7.56 (d, J=
8.1 Hz, 4H), 7.46–7.19 (m, 10H), 7.01–6.91 (m, 2.6H), 6.68 (t, J=
8.4 Hz, 0.4H), 6.20 (s, 0.8H), 5.84 (s, 0.2H), 5.45–5.43 (m, 2H), 5.19 (s,
0.2H), 4.11 (q, J=6.6 Hz, 1.6H), 4.02–3.97 (m, 0.4H), 2.52 (s, 2.4H),
2.31 (s, 0.6H), 1.19 (d, J=7.5 Hz, 2.4H), 1.09 ppm (d, J=7.2 Hz,
0.6H); 13C NMR (100 MHz, CDCl3): d=165.5, 165.1, 156.4, 152.9,
141.2, 140.1, 136.5, 134.5, 130.3, 130.0, 129.9, 128.8, 127.9, 127.7,
127.6, 127.5, 127.0, 125.2, 123.9, 121.9, 118.9, 115.5, 115.3, 113.7,
111.5, 110.5, 108.3, 60.4, 54.6, 50.6, 22.9, 14.1 ppm; MS (ESI): m/z
(%): 628 [M+H]+ (100%), 650 [M+Na]+ (10%); HRMS (ESI): m/z
calcd for C38H31FN3O3S [M+H]+: 628.2065, found: 628.2076; HPLC
(method B): tR =16.14 min (60.0%).
1
as a yellow solid (109 mg, 46%). H NMR (300 MHz, CDCl3): d=8.11
(s, 1H), 7.80 (dd, J=7.2, 1.5 Hz, 1H), 7.56 (d, J=8.4 Hz, 4H), 7.47–
7.41 (m, 3H), 7.38–7.33 (m, 7H), 7.29–7.18 (m, 7H), 7.10–7.03 (m,
2H), 6.18 (s, 1H), 5.44 (s, 2H), 2.29 ppm (s, 6H); 13C NMR (100 MHz,
CDCl3): d=169.5, 165.2, 151.3, 142.2, 141.3, 140.9, 140.4, 137.5,
136.6, 134.7, 130.4, 130.2, 129.0, 128.9, 128.1, 127.8, 127.7, 127.6,
127.2, 125.6, 125.0, 124.8, 123.9, 122.3, 122.0, 121.0, 120.3, 119.1,
114.2, 113.6, 111.7, 110.6, 56.0, 50.8, 21.5, 21.3 ppm; MS (ESI): m/z
(%): 715 [M+H]+ (38%), 737 [M+Na]+ (100%), 753 [M+K]+ (11%);
HRMS (MALDI): m/z calcd for C44H35N4O4S [M+H]+: 715.2374,
found: 715.2369; HPLC (method B): tR =14.07 min (81.9%).
(Z)-Ethyl 2-((1-(biphenyl-4-ylmethyl)indol-3-yl)methylene)-5-(3-
methoxyphenyl)-7-methyl-3-oxo-thiazolo[3,2-a]pyrimidine-6-car-
boxylate (BCL-LZH-42): General procedure A afforded BCL-LZH-42
(Z)-4-(2-((1-(Biphenyl-4-ylmethyl)indol-3-yl)methylene)-7-methyl-
3-oxo-6-(phenylcarbamoyl)thiazolo[3,2-a]pyrimidin-5-yl)phenyl
acetate (BCL-LZH-38): General procedure A afforded BCL-LZH-38
1
as a yellow solid (131 mg, 62%). H NMR (300 MHz, CDCl3): d=8.09
(s, 1H), 7.79–7.76 (m, 0.8H), 7.72–7.68 (m, 0.2H), 7.56–7.53 (m, 4H),
7.45–7.06 (m, 8H), 7.03–6.94 (m, 2H), 7.79 (d, J=7.8 Hz, 1H), 6.67–
6.49 (m, 1H), 6.17 (s, 0.8H), 5.89 (s, 0.2H), 4.12 (q, J=7.2 Hz, 1.6H),
4.01 (q, J=7.2 Hz, 0.4H), 3.76–3.74 (m, 2.4H), 3.50–3.48 (m, 0.6H),
2.46 (s, 2.4H), 3.30 (s, 0.6H), 1.21 (t, J=7.2 Hz, 2.4H), 1.12 ppm (t,
J=6.9 Hz, 0.6H); 13C NMR (100 MHz, CDCl3): d=165.6, 165.2, 159.6,
156.4, 152.8, 141.9, 141.2, 140.6, 140.2, 136.5, 134.5, 130.2, 129.5,
128.8, 128.0, 127.7, 127.5, 127.4, 127.0, 126.9, 125.0, 123.8, 121.8,
1
as a yellow solid (87 mg, 37%). H NMR (300 MHz, [D6]DMSO): d=
10.05 (s, 0.9H), 10.00 (s, 0.1H), 9.09 (s, 0.1H), 8.16 (s, 0.9H), 8.07 (s,
0.9H), 7.96 (s, 0.1H), 7.92 (d, J=7.8 Hz, 1H), 7.65–7.56 (m, 7H), 7.46–
7.19 (m, 11H), 7.14–7.04 (m, 3H), 6.27 (s, 1H), 5.66 (s, 1.8H), 5.62 (s,
0.2H), 2.23 (s, 2.7H), 2.21 (s, 0.3H), 2.14 (s, 2.7H), 2.11 ppm (s, 0.3H);
13C NMR (100 MHz, [D6]DMSO): d=169.0, 165.0, 164.4, 152.9, 150.3,
141.0, 139.6, 138.6, 137.2, 136.2, 136.0, 131.7, 128.9, 128.7, 128.0,
914
ꢀ 2011 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
ChemMedChem 2011, 6, 904 – 921