You, Zhao & Li
FULL PAPER
removal of the solvent, the resulting residue was sub-
jected to column chromatography (petroleum ether/
AcOEt/NEt3, V∶V∶V=100∶100∶1) to give com-
jected to flash chromatography (CH2Cl2/MeOH, V∶V
=30∶1) to give compound 9 as a sticky solid (0.67 g,
72%). 1H NMR (CDCl3, 400 MHz) δ: 8.40 (s, 1H), 7.85
(s, 2H), 7.30 (s, 2H), 4.82 (s, 2H), 4.66 (s, 4H), 4.21 (s,
2H), 4.14 (s, 4H), 3.31 (t, J=7.5 Hz, 6H), 3.18 (t, J=
6.9 Hz, 6H), 1.57—1.49 (m, 12H), 1.30—1.28 (m, 36H),
0.89—0.87 (m, 18H); 13CNMR (CDCl3, 125 MHz) δ:
169.3, 167.9, 167.6, 167.3, 167.2, 150.2, 141.4, 126.2,
109.5, 72.5, 68.3, 47.1, 47.1, 46.3, 40.9, 40.8, 31.5, 31.5,
31.5, 28.7, 28.7, 27.6, 27.5, 26.7, 26.6, 26.5, +22.6, 22.5,
14.0, 14.0; MS (ESI) m/z: 1040.0 ([M+Na] ); HRMS
(ESI) calcd for C55H97N6O11 ([M+H]+) 1017.7210,
found 1017.7209.
1
pound 313 as a yellow solid (1.80 g, 87%). H NMR
(CD3COCD3, 300 MHz) δ: 9.47 (s, 1H), 7.16 (d, J=8.4
Hz, 1H), 6.68 (br, 1H), 6.05 (dd, J1=8.4 Hz J2=2.1 Hz
1H), 5.91 (d, J=2.1 Hz, 1H), 5.43 (br, 1H); MS (ESI)
m/z: 136.9 ([M]+).
Compound 5: To a stirred solution of compounds 3
(0.50 g, 3.68 mmol) and 414 (0.25 g, 1.54 mmol) in
ethanol (35 mL) was added a saturated solution of po-
tassium hydroxide in ethanol (3 mL). The solution was
refluxed for 24 h and cooled to room temperature and
then diluted with water (300 mL). The formed precipi-
tate was filtrated and washed with water and dried in
vacuo to give compound 5 as a yellow solid (0.42 g,
Compound 1: To a solution of compounds 5 (0.02 g,
0.076 mmol), 9 (0.14 g, 0.14 mmol) and lithium chlo-
ride (0.05 g, 1.19 mmol) in N-methyl pyrrolidone (NMP,
1 mL) and pyridine (0.25 mL) was added triphenyl
phosphate (0.13 mL, 0.42 mmol). The mixture was
stirred at 90 ℃ for 20 h and diluted with water (20 mL)
and acidified with diluted hydrochloric acid (pH=2).
The solvent was removed with a rotavapor. The ob-
tained slurry was triturated with water (5 mL) and the
mixture was extracted with ethyl acetate (25 mL×2).
The organic phases were combined and washed with
water (25 mL×2) and brine (25 mL), and dried over
sodium sulfate. Upon removal of the solvent with a ro-
tavapor, the resulting residue was subjected to column
chromatography (CH2Cl2/MeOH, V∶V=20∶1) to
1
76%). H NMR (CDCl3, 300 MHz) δ: 8.68 (d, J=7.5
Hz, 2H), 8.58 (d, J=8.4 Hz, 2H), 8.16 (d, J=8.4 Hz,
2H), 8.02 (t, J=7.5 Hz, 1H), 7.68 (d, J=8.7 Hz, 2H),
7.32 (s, 2H), 7.01 (dd, J1=8.7 Hz, J2=1.2 Hz, 2H),
4.08 (br, 4H); 13C NMR (CDCl3, 125 MHz) δ: 156.6,
155.8, 149.7, 147.7, 137.7, 136.3, 128.7, 122.4, 121+.7,
118.8, 115.9, 109.8; MS (ESI) m/z: 364.1+([M+H] );
HRMS (ESI) calcd for C23H18N5 ([M+H] ) 364.1557,
found 364.1562.
Compound 8: A suspension of compounds 615 (0.40
g, 2.17 mmol), 79 (2.50 g, 6.68 mmol), potassium iodide
(0.50 g, 3.01 mmol) and potassium carbonate (3.30 g,
23.9 mmol) in acetone (25 mL) was stirred at 60 ℃ for
12 h and then concentrated with a rotary evaporator.
The resulting slurry was triturated with water (20 mL)
and dichloromethane (50 mL). The organic phase was
separated and washed with water (20 mL) and brine (20
mL), and dried over sodium sulfate. Upon removal of
the solvent, the resulting residue was subjected to col-
umn chromatography (CH2Cl2/acetone, V∶V=6∶1) to
1
give compound 1 as a yellow solid (50 mg, 35%). H
NMR (CDCl3, 300 MHz) δ: 9.89 (s, 2H), 8.76—8.72 (m,
4H), 8.53 (s, 2H), 8.45 (s, 2H), 8.24 (d, J=8.4 Hz, 2H),
8.04—8.01 (m, 3H), 7.81 (d, J=8.7 Hz, 2H), 7.53—
7.51 (m, 8H), 4.83—4.77 (m, 12H), 4.18—4.15 (m,
12H), 3.33—3.17 (m, 24H), 1.57—1.36 (m, 24H), 1.29
—1.06 (m, 72H), 0.88—0.71 (m, 36H); 13C NMR
(CDCl3, 125 MHz) δ: 168.8, 167.8, 166.6, 166.5, 164.4,
155.8, 155.0, 150.1, 147.9, 140.1, 139.1, 137.2, 135.5,
130.6, 127.2, 125.1, 121.9, 121.4, 119.5, 117.5, 108.2,
72.3, 68.6, 46.6, 45.9, 45.7, 40.5, 40.2, 31.1, 31.0, 31.0,
28.3, 28.2, 27.1, 27.0, 26.2, 26.1, 26.1, 22.1, 22.0, 22.0,
13.5, 13.5, 13.4; MS (MALDI-TOF) m/z: 2361.6 ([M+
Na]+); HRMS (MALDI-TOF) calcd for C133H206N17O20
([M+H]+) 2361.5620, found 2361.5653.
1
give compound 8 as a colorless oil (1.70 g, 75%). H
NMR (CDCl3, 300 MHz) δ: 8.41 (s, 1H), 7.69 (s, 2H),
7.33 (s, 2H), 4.82 (s, 2H), 4.69 (s, 4H), 4.18 (d, J=3.6
Hz, 2H), 4.09 (d, J=4.2 Hz, 4H), 3.88 (s, 3H), 3.29 (t,
J=7.5 Hz, 6H), 3.16 (t, J=7.2 Hz, 6H), 1.54—1.49 (m,
12H), 1.29—1.27 (m, 36H), 0.89—0.87 (m, 18H); 13C
NMR (CDCl3, 125 MHz) δ: 169.0, 167.6, 167.2, 166.6,
165.7, 150.5, 141.7, 126.0, 109.4, 72.7, 68.6, 52.4, 47.0,
46.9, 46.1, 41.0, 40.8, 31.5, 31.5, 31.5, 28.7, 27.5, 26.6,
26.5, 26.5,+22.5, 22.5, 14.0, 13.9; MS (ESI) m/z: 1053.9
([M+Na] ); HRMS (ESI) calcd for C56H98N6O11Na
([M+Na]+) 1053.7186, found 1053.7221.
Results and discussion
The synthesis of compound 1 is shown in Scheme 1.
Thus, compound 2 was first reduced with iron powder
and ammonium chloride in aqueous ethanol to diamine
3, which was then coupled with 4 in the presence of
potassium hydroxide in refluxing ethanol affording di-
amine 5 in 76% yield. Then, compound 8 was produced
in 75% yield from the reaction of 6 and an excess
amount of 7 in hot acetone and further hydrolyzed with
lithium hydroxide to afford acid 9 in 72% yield. The
acid was finally coupled with 5 to produce 1 in 35%
Compound 9: A solution of compound 8 (0.94 g,
0.91 mmol) and lithium hydroxide monohydrate (0.10 g,
2.38 mmol) in methanol (3 mL) and water (2 mL) was
stirred at room temperature for 7 h and then acidified
with diluted hydrochloric acid to pH=2. The mixture
was concentrated with a rotavapor and the resulting
slurry triturated with dichloromethane (50 mL). The
organic phase was washed with water (25 mL×2) and
brine (25 mL), and dried over sodium sulfate. The sol-
vent was then removed and the obtained residue sub-
1
yield. Compound 1 was characterized by H and 13C
NMR and (high resolution) mass spectrometer.
1548
© 2010 SIOC, CAS, Shanghai, & WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
Chin. J. Chem. 2010, 28, 1547— 1552