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7.1.27. Compound 29b
7.1.30. Compound 32
The synthesis and characterization of 29b has recently been
Compound 17 (0.109 g, 0.27 mmol) was subjected to ester
hydrolysis according to General method C using K2CO3 (0.114 g,
0.82 mmol), MeCN (1.5 mL) and H2O (1.0 mL). Microwave heating
for 45 min followed by work-up produced the corresponding car-
boxylic acid (0.106 g, 99%). Compound 32 was prepared according
to general method D, using the carboxylic acid derived from 17
(0.054 g, 0.14 mmol), hydrochloride 4 (0.054 g, 0.20 mmol), HATU
(0.062 g, 0.16 mmol) and DIEA (0.22 mL, 1.3 mmol) in DCM
(2.0 mL). The reaction was stirred at 40 °C over night. Purification
by RP-Si column chromatography (MeCN/H2O 1:4, 1:1, 100%
MeCN) followed by RP-HPLC. Yield: 0.021 g, 26% of the title com-
pound as a white solid. 1H NMR (approx. 10:1 diastereomeric ratio,
major stereoisomer reported, CDCl3) d 10.99 (s, 1H), 7.49–7.46 (m,
3H), 7.34–7.20 (m, 7H), 6.70 (m, 1H), 6.12 (s, 1H), 5.84 (ddd,
J = 17.1, 10.3, 8.4 Hz, 1H), 5.33 (s, 1H), 5.37 (ddd, J = 17.1, 1.8,
0.8 Hz, 1H), 5.17 (ddd, J = 10.3, 1.8, 0.7 Hz, 1H), 3.65 (m, 2H), 2.95
(m, 2H), 2.91 (m, 1H), 2.29 (s, 3H), 2.23 (m, 1H), 1.86 (dd, J = 8.6,
5.4 Hz, 1H), 1.42 (m, 1H), 1.21 (dd, J = 9.7, 5.4 Hz, 1H), 1.57 (m,
1H), 1.07 (m, 1H), 0.98 (m, 1H). 13C NMR (approx. 10:1 diastereo-
meric ratio, major stereoisomer reported, CDCl3) d 168.9, 168.4,
151.8, 148.9, 139.0, 123.7, 131.9, 130.3, 130.2, 128.9, 128.6,
128.5, 128.3, 126.5, 118.9, 118.6, 67.1, 42.8, 41.6, 37.1, 35.1, 31.3,
23.6, 15.8, 6.7, 6.2. RP-HPLC purity: column C: 97.6%; column D:
>99%. HRMS calcd for C30H33ClN5O5S (M+H+) 610.1891, found:
610.1888.
published by us.26
7.1.28. Compound 30
Compound 15 (0.069 g, 0.18 mmol) was subjected to ester
hydrolysis according to general method C using K2CO3 (0.049 g,
0.36 mmol), MeCN (0.75 mL) and H2O (0.50 mL). Microwave heat-
ing for 55 min followed by work-up produced the corresponding
carboxylic acid (0.0962 g, 100%). Compound 30 was prepared
according to general method D, using the carboxylic acid derived
from 15 (0.047 g, 0.13 mmol), hydrochloride
4
(0.051 g,
0.19 mmol), HATU (0.059 g, 0.15 mmol) and DIEA (0.20 mL,
1.1 mmol) in DCM (2.0 mL). The reaction was stirred at 40 °C over
night. Purification by RP-Si column chromatography (MeCN/H2O
1:1, 100% MeCN) followed by RP-HPLC. Yield: 0.017 g, 23% of the
title compound as a white solid. 1H NMR (1:1 diastereomeric ratio,
CDCl3) d 11.0 (s, 1H), 10.9 (s, 1H), 7.47 (m, 6H), 7.33 (m, 2H), 7.29
(m, 2H), 6.51 (m, 2H), 6.17 (s, 1H), 6.15 (s, 1H), 5.88–5.77 (m, 2H),
5.54 (s, 1H), 5.53 (s, 1H), 5.37 (ddd, J = 17.2, 1.8, 0.7 Hz, 1H), 5.19
(ddd, J = 17.2, 1.7, 0.7 Hz, 1H), 5.15 (ddd, J = 10.3, 1.8, 0.7 Hz, 1H),
5.10 (ddd, J = 10.3, 1.7, 0.7 Hz, 1H), 3.38 (m, 4H), 2.95 (m, 2H),
2.29 (s, 3H), 2.27 (s, 3H), 2.24 (m, 1H), 2.04 (dd, J = 8.3, 5.4 Hz,
1H), 1.88 (m, 1H), 1.85 (dd, J = 8.6, 5.4 Hz, 1H), 1.62–1.49 (m,
4H), 1.42 (m, 1H), 1.22 (dd, J = 9.6, 5.4 Hz, 1H), 1.15–1.05 (m,
4H), 1.02–0.95 (m, 4H), 0.97 (s, 9H), 0.96 (s, 9H). 13C NMR (1:1 dia-
stereomeric ratio, CDCl3) d 169.0, 168.9, 168.7, 168.6, 151.9, 151.8,
148.9, 148.7, 132.8, 132.4, 131.9, 131.6, 130.3 (two peaks), 130.2
(two peaks), 128.5, 128.3 (two peaks), 128.1, 118.9, 118.6, 118.3,
118.1, 67.1, 66.8, 42.6 (two peaks), 41.7, 41.6, 38.0 (two peaks),
37.2, 35.5, 31.2, 30.9, 30.1, 30.0, 29.6 (two peaks), 25.2, 23.7,
15.8, 15.7, 6.7, 6.6, 6.2, 5.8. RP-HPLC purity: column C: 96.7%; col-
umn D: 98.3%. HRMS calcd for C28H37ClN5O5S (M+H+) 590.2204,
found: 590.2227.
7.1.31. Compound 33
Compound 18 (0.058 g, 0.16 mmol) was subjected to ester
hydrolysis according to general method C using K2CO3 (0.045 g,
0.32 mmol), MeCN (0.75 mL) and H2O (0.75 mL). Microwave heat-
ing for 45 min followed by work-up produced the corresponding
carboxylic acid. Compound 33 was prepared according to general
method D, using the carboxylic acid derived from 18, hydrochlo-
ride 4 (0.054 g, 0.20 mmol), HATU (0.075 g, 0.20 mmol) and DIEA
(0.22 mL, 1.3 mmol) in DCM (2.5 mL). The reaction was stirred at
40 °C for 27 h followed by room temperature for 36 h. Purification
by column chromatography (isohexane/EtOAc 4:1) followed by RP-
HPLC. Yield: 0.025 g, 28% (two steps) of the title compound as a
white solid. 1H NMR (CD3OD) d 7.43–7.30 (m, 10H), 6.44 (s, 1H),
6.43 (s, 1H), 5.67 (m, 1H), 5.31 (ddd, J = 17.2, 1.8, 0.7 Hz, 1H),
5.30 (ddd, J = 17.2, 1.8, 0.7 Hz, 1H), 5.13 (dd, J = 10.3, 1.8 Hz, 1H),
5.12 (dd, J = 10.3, 1.8 Hz, 1H), 4.09 (d, J = 16.8 Hz, 1H), 4.08 (d,
J = 16.8 Hz, 1H), 4.02 (d, J = 16.8 Hz, 1H), 4.01 (d, J = 16.8 Hz, 1H),
2.94 (m, 1H), 2.29 (m, 1H), 2.24 (s, 3H), 1.88 (dd, J = 8.2, 5.5 Hz,
1H), 1.39 (m, 1H), 1.21 (m, 2H), 1.06 (m, 2H). 13C NMR (CD3OD) d
174.0, 170.8, 170.6, 153.1 (two peaks), 150.0, 149.9, 135.1 (two
peaks), 134.3, 129.5, 129.4, 129.3, 126.8, 122.1, 118.6, 63.3 (two
peaks), 45.3, 43.1, 43.0, 35.3 (two peaks), 32.1, 22.7, 16.5 (two
peaks), 6.5 (two peaks). RP-HPLC purity: column C: 97.7%; column
D: >99%. HRMS calcd for C24H28ClN6O6S (M+H+) 563.1480, found:
563.1494.
7.1.29. Compound 31
Compound 16 (0.102 g, 0.24 mmol) was subjected to ester
hydrolysis according to General method C using K2CO3 (0.100 g,
0.72 mmol), MeCN (1.5 mL) and H2O (1.0 mL). Microwave heating
for 45 min followed by work-up produced the corresponding car-
boxylic acid. Compound 31 was prepared according to general
method D, using the carboxylic acid derived from 16 (0.049 g,
0.12 mmol), hydrochloride
4
(0.048 g, 0.18 mmol), HATU
(0.055 g, 0.15 mmol) and DIEA (0.20 mL, 1.1 mmol) in DCM (2.0
mL). The reaction was stirred at 40 °C over night. Purification by
RP-Si column chromatography (MeCN/H2O 1:4, 100% MeCN) fol-
lowed by RP-HPLC. Yield: 0.023 g, 26% of the title compound as
1 H NMR
its TFA salt, as a white solid.
(1:1 diastereomeric ratio,
CDCl3) d 10.84 (s, 1H), 10.82 (s, 1H), 7.37 (m, 6H), 7.28 (m, 4H),
7.18 (m. 1H), 7.11 (m, 1H), 5.91 (ddd, J = 17.1, 10.4, 8.4 Hz, 1H),
5.68 (ddd, J = 17.1, 10.3, 8.7 Hz, 1H), 5.56 (s, 1H), 5.54 (s, 1H),
5.32 (dd, J = 17.1, 2.1 Hz, 1H), 5.21 (dd, J = 17.1, 2.0 Hz, 1H),
5.12–5.07 (m, 2H), 4.02–3.58 (m, 18H), 3.02–2.78 (m, 8H), 2.29
(s, 2 ꢀ 3H, overlapping), 2.23 (m, 2H), 1.98 (dd, J = 8.4, 5.6 Hz,
1H), 1.82 (dd, J = 8.7, 5.1 Hz, 1H), 1.50 (dd, J = 9.6, 5.1 Hz, 1H),
1.47 (dd, J = 9.5, 5.6 Hz, 1H), 1.41–1.34 (m, 2H), 1.32–1.24 (m,
2H), 1.1–1.02 (m, 4H). 13C NMR (1:1 diastereomeric ratio, CDCl3)
d 169.9, 169.4, 167.9, 167.7, 152.3 (two peaks), 149.5 (two peaks),
133.3, 133.1 (two peaks), 132.9, 129.2 (two peaks), 129.1, 129.0,
128.7, 128.6, 127.4, 127.2, 121.5, 121.4, 118.4, 118.3, 66.0, 65.6,
64.1 (two peaks), 63.8, 63.7, 55.7, 55.1, 53.9, 53.7, 51.7, 51.4,
42.1, 41.2, 36.2, 35.7 (two peaks), 35.0, 31.4, 31.3, 25.3, 22.4,
15.8 (two peaks), 6.6, 6.4, 6.3, 6.2. RP-HPLC purity: column C:
>99%; column D: >99%. HRMS calcd for C28H36ClN6O6S (M+H+)
619.2106, found: 619.2108.
7.1.32. Compound 34
Compound 19 (0.063 g, 0.16 mmol) was subjected to ester
hydrolysis according to general method C using K2CO3 (0.046 g,
0.33 mmol), MeCN (1.25 mL) and H2O (1.0 mL). Microwave heating
for 45 min followed by work-up produced the corresponding car-
boxylic acid. Compound 34 was prepared according to general
method D, using the carboxylic acid derived from 19 (0.061 g,
0.16 mmol), hydrochloride 4 (0.059 g, 0.22 mmol), HATU (0.075 g,
0.20 mmol) and DIEA (0.22 mL, 1.3 mmol) in DCM (2.5 mL). The
reaction was stirred at 40 °C for 27 h followed by room tempera-
ture for 36 h. Work-up by extractions followed by RP-HPLC. Yield:
0.032 g, 34% (two steps) of the title compound as a white solid. 1
NMR (1:1 diastereomeric ratio, CD3OD) d 7.43–7.34 (m, 10H), 6.00
H