11938
J. Zhu et al. / Tetrahedron 62 (2006) 11933–11941
of formic acetic anhydride (0.26 g, 3.00 mmol) in THF
(2 mL). The solution was stirred at room temperature for
0.5 h and then concentrated under reduced pressure. The re-
sulting residue was dissolved in chloroform (20 mL). The
solution was then washed with saturated sodium bicarbonate
solution (10 mL), water (10 mLꢁ2), brine (10 mL) and
dried over sodium sulfate. After the solvent was removed
under reduced pressure, the crude product was purified by
recrystallization from THF and petroleum ether to give 8
4.23–4.10 (m, 8H), 1.94–1.86 (m, 4H), 1.51–1.42 (m,
10H), 0.99–0.94 (m, 6H). 19F NMR (CDCl3) d: ꢂ76.01.
MS (MALDI-TOF): m/z 771 [M+1]+, 793 [M+Na]+, 809
[M+K]+. HRMS (MALDI-TOF) Calcd for C36H41N4O8F6:
771.2802. Found: 771.2823.
4.1.6. Compound 13. A solution of compounds 9 (0.51 g,
2.00 mmol), 1224a (0.20 g, 1.00 mmol), DCC (0.45 g,
2.20 mmol) and HOBt (0.30 g, 2.20 mmol) in THF
(25 mL) was stirred at room temperature for 12 h and then
concentrated in vacuo. The resulting residue was triturated
with chloroform (50 mL). The organic phase was then
washed with saturated sodium bicarbonate solution
(25 mL), water (25 mLꢁ2), brine (25 mL) and dried over
sodium sulfate. After the solvent was removed under reduced
pressure, the crude product was purified by column chroma-
tography (dichloromethane/acetone 100:1 to 50:1) to give 13
1
as pale yellow solid (0.37 g, 65%). H NMR (CDCl3) d:
11.07 (br, 1H), 8.40 (d, J¼1.7 Hz, 1H), 8.30 (dd,
J1¼2.9 Hz, J2¼9.0 Hz, 1H), 7.94 (d, J¼2.8 Hz, 1H), 7.61
(s, 1H), 7.05 (d, J¼9.0 Hz, 1H), 4.29–4.25 (m, 2H), 1.95–
1
1.86 (m, 2H), 1.57–1.47 (m, 2H), 1.04–0.99 (m, 3H). H
NMR (DMSO-d6) d: 8.63 (s, 1H), 8.22 (s, 1H), 7.87 (d,
J¼2.7 Hz, 1H), 7.66 (dd, J1¼2.8 Hz, J2¼8.9 Hz, 1H), 7.08
(d, J¼9.0 Hz, 1H), 4.01–3.97 (m, 2H), 1.72–1.62 (m, 2H),
1.50–1.37 (m, 2H), 0.93–0.88 (m, 3H). MS (ESI): m/z 238
[M+H]+, 260 [M+Na]+. Anal. Calcd for C12H15NO4: C,
60.75; H, 6.37; N, 5.90. Found: C, 60.70; H, 6.28; N, 5.79.
1
as a pale yellow solid (0.40 g, 65%). H NMR (CDCl3) d:
9.65 (s, 1H), 8.21 (d, J¼7.8 Hz, 2H), 8.04 (s, 2H), 7.39 (t,
J¼7.8 Hz, 1H), 6.52 (s, 2H), 4.01–3.96 (m, 11H), 3.65 (s,
4H), 1.85–1.72 (m, 8H), 1.59–1.38 (m, 8H), 1.02–0.97 (m,
6H), 0.90–0.85 (m, 6H). 13C NMR (CDCl3) d: 162.4,
155.9, 143.1, 141.2, 134.7, 130.1, 128.6, 125.2, 121.7, 108.7,
99.4, 69.9, 68.8, 64.2, 31.5, 19.4, 19.2, 13.9, 13.8. MS
(MALDI-TOF): m/z 687 [M+Na]+. HRMS (MALDI-TOF)
Calcd for C37H52N4O7Na+ [M+Na]+: 687.3733. Found:
687.3728.
4.1.3. Compound 2. To a stirred solution of compounds 8
(0.24 g, 1.00 mmol) and 9 (0.13 g, 050 mmol) in DMF
(10 mL) and THF (10 mL) were added HATU (0.40 g,
1.05 mmol) and DIEA (0.2 mL). The mixture was stirred at
room temperature for 20 h and then concentrated in vacuo.
The resulting residue was triturated with methanol
(10 mL). The mixture was stirred for 0.5 h. The precipitate
formed was filtered, washed with ether and recrystallized
from methanol and chloroform to give 2 as a yellow solid
4.1.7. Compound 15. A solution of compound 14 (0.84 g,
5.00 mmol), acetic anhydride (1.02 g, 10.0 mmol) and
DMAP (10 mg) in THF (25 mL) was stirred at room temper-
ature for 1 h. After workup, the crude product was subjected
to column chromatography (AcOEt/petroleum ether 1:5) to
1
(0.29 g, 84%). H NMR (CDCl3) d: 10.14 (s, 2H), 9.31 (s,
2H), 9.15 (s, 2H), 8.31 (dd, J1¼2.7 Hz, J2¼8.9 Hz, 2H),
8.25 (d, J¼2.7 Hz, 1H), 8.01 (s, 2H), 6.95 (d, J¼9.0 Hz,
2H), 6.59 (s, 2H), 4.22–4.18 (m, 4H), 4.19–4.14 (m, 4H),
1.91–1.77 (m, 8H), 1.52–1.43 (m, 8H), 0.99–0.93 (m,
1
give 15 as a white solid (0.84 g, 80%). H NMR (CDCl3)
d: 8.26 (dd, J1¼3.0 Hz, J2¼9.0 Hz, 1H), 7.85 (d, J¼
3.0 Hz, 1H), 7.06 (d, J¼9.0 Hz, 1H), 4.08 (s, 3H), 2.20 (s,
3H). MS (EI): m/z 209 [M]+. Anal. Calcd for C10H11NO4:
C, 57.41; H, 5.30; N, 6.70. Found: C, 57.29; H, 5.25; N, 6.60.
1
12H). H NMR (DMSO-d6) d: 10.03 (s, 2H), 9.24 (s, 1H),
8.24 (s, 2H), 8.17 (d, J¼2.8 Hz, 2H), 7.83 (dd, J1¼2.8 Hz,
J2¼8.9 Hz, 2H), 7.23 (d, J¼9.0 Hz, 2H), 6.87 (s, 1H),
4.27–4.23 (m, 4H), 4.17–4.13 (m, 4H), 1.85–1.69 (m, 8H),
1.49–1.35 (m, 8H), 0.94–0.88 (m, 12H). 13C NMR (CDCl3)
d: 162.4, 161.6, 161.5, 159.3, 152.8, 152.3, 145.0, 131.8,
124.0, 122.6, 122.5, 122.0, 120.9, 120.0, 115.0, 114.8,
114.3, 98.6, 69.2, 68.6, 30.7, 30.4, 18.5, 13.6. MS
(MALDI-TOF): m/z 691 [M+1]+, 713 [M+Na]+, 729
[M+K]+. HRMS (MALDI-TOF) Calcd for C38H51N4O8
[M+H]+: 691.3687. Found: 691.3701.
4.1.8. Compound 4. To a stirred solution of compounds 13
(0.14 g, 0.21 mmol) and 15 (0.094 g, 0.45 mmol) in DMF
(10 mL) were added HATU (0.17 g, 0.45 mmol) and DIEA
(0.1 mL). The mixture was stirred at room temperature for
12 h and then the solvent was removed under reduced pres-
sure. The resulting residue was triturated with methanol
(3 mL). The yellow precipitate formed was filtered, dried
in vacuo and then subjected to column chromatography
(CH2Cl2/AcOEt 10:1) to give 4 as a light-yellow solid
4.1.4. Compound 10. Compound 10 was prepared as a white
solid (95%) from the reaction of compound 7 and trifluoro-
acetic anhydride in THF according to the procedure de-
1
(0.15 g, 68%). H NMR (CDCl3) d: 10.18 (s, 2H), 9.57 (s,
2H), 9.43 (s, 2H), 8.27–8.20 (m, 6H), 7.94 (d, J¼2.6 Hz,
2H), 7.40 (t, J¼7.7 Hz, 1H), 6.98 (d, J¼9.1 Hz, 2H), 6.53
(s, 2H), 4.06–3.99 (m, 17H), 2.16 (s, 6H), 1.86–1.72 (m,
8H), 1.60–1.39 (m, 8H), 1.02–0.97 (m, 6H), 0.90–0.85 (m,
6H). 13C NMR (CDCl3) d: 169.1, 162.9, 162.3, 155.9,
153.6, 145.9, 134.8, 132.6, 128.5, 125.3, 125.2, 123.6, 122.2,
121.1, 120.3, 116.2, 112.1, 97.3, 69.0, 68.9, 64.3, 56.4, 31.5,
31.4, 24.3, 19.2, 13.8, 13.8. MS (MALDI-TOF): m/z 1047
[M+H]+, 1069 [M+Na]+. HRMS (MALDI-TOF) Calcd for
C57H71N6O13 [M+H]+: 1047.5072. Found: 1047.5074.
1
scribed above for the preparation of 8. H NMR (CDCl3)
d: 9.07 (s, 1H), 8.29 (dd, J1¼2.8 Hz, J2¼9.0 Hz, 1H), 8.22
(d, J¼2.8 Hz, 1H), 7.04 (d, J¼9.1 Hz, 1H), 4.23 (t,
J¼6.8 Hz, 2H), 1.95–1.90 (m, 2H), 1.48–1.43 (m, 2H),
0.96 (t, J¼6.5 Hz, 3H). 19F NMR (CDCl3) d: ꢂ76.03. MS
(ESI): m/z 305 [M]+. Anal. Calcd for C13H14F3NO4: C,
51.15; H, 4.62; N, 4.59. Found: C, 51.02; H, 4.70; N, 4.51.
4.1.5. Compound 3. Compound 3 was prepared as a white
solid (65%) from the reaction of 10 and 1122b according to
the procedure described above for the preparation of 2. H
1
4.1.9. Compound 17. To a solution of aniline 6 (0.93 g,
4.20 mmol) in THF (20 mL) was added n-butyl isocyanide
16 (0.60 mL). The solution was stirred at room temperature
NMR (CDCl3) d: 10.00 (s, 2H), 9.24 (s, 1H), 9.15 (s, 2H),
8.12–8.16 (m, 4H), 7.02 (d, J¼9.8 Hz, 2H), 6.55 (s, 1H),