6
M. Cavazzini et al. / Tetrahedron xxx (2013) 1e7
obtain the title compound 9 (0.430 g, 42%) as a crystalline red solid,
mp 195e196 ꢀC; nmax(KBr) 3036, 2957, 2930, 2871, 1762, 1702, 1600,
(0.342 g, 2.28 mmol) and K2CO3 (8.1 g, 57.0 mmol). The resulting
suspension was heated at reflux for 12 h. After this time, it was
cooled at room temperature and the solid removed by filtration
over a fritted septum. The organic solvent was removed by evap-
oration under reduced pressure and the residue was purified by
column chromatography (SiO2; CHCl3) to afford the title compound
11 (3.40 g, 81%) as a white solid, mp 189e191 ꢀC; nmax(KBr) 2981,
1532, 1377 cmꢁ1
; dH (400 MHz, CD2Cl2) 0.96 (6H, t, J 7.4 Hz, CH3),
1.35 (4H, sex, J 7.4 Hz, CH2),1.58 (4H, m, CH2),1.98 (2H, quin, J 7.2 Hz,
CH2), 2.98 (3H, s, NCH3), 3.30 (4H, br t, J 7.5 Hz, CH2), 3.44 (2H, br t, J
7.2 Hz, CH2), 3.72 (2H, t, J 7.2 Hz, CH2), 6.64 (2H, d, J 8.9 Hz, ArH),
6.68 (2H, d, J 8.9 Hz, ArH), 6.83 (1H, d, J 16.7 Hz, H-styryl), 6.85 (1H,
d, J 16.7 Hz, H-styryl), 7.42e7.36 (6H, m, ArH, H-styryl), 7.75e7.70
(2H, m, ArH), 7.85e7.80 (2H, m, ArH); dC (100.6 MHz, CD2Cl2)14.1,
20.7, 26.3, 29.8, 36.2, 38.5, 50.3, 51.0, 108.7, 109.5, 111.8, 112.4, 114.7
(m), 115.2 (m), 123.4, 124.0, 125.2, 128.5, 128.6, 132.5, 134.3, 136.7
(m), 137.0 (m), 143.6 (m), 146.0 (m), 149.1, 149.9, 168.6. HRMS (ESI):
MNaþ, found 720.31928. C42H43F4N3NaO2 requires 720.31891.
2939, 1762, 1736, 1711, 1614, 1405, 1392 cmꢁ1
; dH (400 MHz, CDCl3)
2.22 (2H, quin, J 6.3 Hz, CH2), 2.38 (3H, d, J 1.2 Hz, CH3Ar), 3.93 (2H,
t, J 6.3 Hz, CH2), 4.08 (2H, t, J 6.3 Hz, CH2), 6.12 (1H, m, ArH), 6.70
(1H, d, J 2.5 Hz, ArH), 6.75 (1H, dd, J 8.8, 2.5 Hz, ArH), 7.45 (1H, d, J
8.8 Hz, ArH), 7.70e7.75 (2H, m, ArH), 7.82e7.86 (2H, m, ArH); dC
(100.6 MHz, CDCl3) 18.6, 28.1, 35.3, 66.2, 101.5, 112.0, 112.4, 113.7,
123.3, 125.5, 132.1, 134.0, 152.5, 155.2, 161.2, 161.7, 168.3; HRMS
(ESI): MNaþ, found 386.10029. C21H17NNaO5 requires 386.09989.
4.1.7. N1-(4-(4-(4-(Dibutylamino)styryl)-2,3,5,6-tetrafluorostyryl)
phenyl)-N1-methylpropane-1,3-diamine (10). To a suspension of 9
(0.210 g, 0.301 mmol) in absolute EtOH (25 ml) was added hydra-
zine monohydrate (0.103 g, 2 mmol) at room temperature and then
the mixture was treated at reflux. The reaction was followed by TLC
over silica plates (CH2Cl2/MeOH 8:2). After approximately 8 h, the
starting product 9 was undetectable. The mixture was cooled at
room temperature and filtered over a fritted glass septum. The solid
was washed with EtOH (5 ml) and MeOH (5 ml). The filtrate was
evaporated under reduced pressure. The residue was purified by
column chromatography (SiO2; CH2Cl2/MeOH/aqNH3 9:1:0.1) to
give the title compound 10 (0.154 g, 90%) as a bright orange solid, mp
125e127 ꢀC; nmax(KBr) 3425, 2954, 2929, 2870, 1600, 1521, 1480,
1368, 1188; dH (400 MHz, CD2Cl2þ1% CD3OD) 0.95 (6H, t, J 7.4 Hz,
CH3), 1.36 (4H, sex, J 7.4 Hz, CH2), 1.57 (4H, m, CH2), 1.77 (2H, quin, J
7.1 Hz, CH2), 2.74 (2H, t, J 7.1 Hz, CH2), 2.96 (3H, s, NCH3), 3.29 (4H, br
t, J 7.6 Hz, CH2), 3.41 (2H, t, J 7.4 Hz, CH2), 6.62 (2H, d, J 8.9 Hz, ArH),
6.68 (2H, d, J 8.9 Hz, ArH), 6.82 (1H, d, J 16.6 Hz, H-styryl), 6.84 (1H,
d, J 16.6 Hz, H-styryl), 7.36e7.42 (6H, m, H-styryl, ArH); dC
(100.6 MHz, CD2Cl2þ1% CD3OD) 14.1, 20.7, 29.8, 30.0, 38.5, 39.6,
50.4, 51.1, 111.9, 112.4, 114.7 (m), 115.2 (m), 124.2, 125.3, 128.6, 136.8,
137.1, 143.7 (m), 146.1 (m), 149.2, 150.1; HRMS (ESI): MHþ, found
568.33072. C34H42F4N3 requires 568.33094.
4.1.10. 7-(3-Aminopropoxy)-4-methyl-2H-chromen-2-one (12). To
a suspension of 11 (1.5 g, 4.13 mmol) in MeOH (60 ml) was added
hydrazine monohydrate (0.310 g, 6.20 mmol) at room temperature.
The mixture was treated at reflux until complete consumption of
starting product was confirmed by TLC over silica plates (CHCl3).
Then the solvent was evaporated under reduced pressure and the
solid residue was purified by column chromatography (neutral
Al2O3; CH2Cl2/MeOH/30%-aqNH3 9:1:0.1) to give the title compound
12 (0.789 g, 82%) as a yellow solid, mp 137e138 ꢀC; nmax(KBr) 3319,
2942, 2871, 1713, 1618, 1388, 1291, 1150 cmꢁ1
; dH (400 MHz, CDCl3)
1.96 (2H, quin, J 6.5 Hz, CH2), 2.39 (3H, d, J 1.2 Hz, CH3Ar), 2.93 (2H, t,
J 6.5 Hz, CH2), 4.12 (2H, t, J 6.5 Hz, CH2), 6.12 (1H, m, ArH), 6.82 (1H,
d, J 2.4 Hz, ArH), 6.84 (1H, dd, J 8.8, 2.4 Hz, ArH), 7.48 (1H, d, J 8.8 Hz,
ArH); dC (100.6 MHz, CDCl3) 18.6, 32.7, 39.0, 66.4, 101.5, 111.9, 112.6,
113.6, 125.5, 152.4, 155.3, 161.3, 162.1; HRMS (ESI): MHþ, found
234.11252. C13H16NO3 requires 234.11247.
4.1.11. N-(3-(4-Methyl-2-oxo-2H-chromen-7-yloxy)propyl)acet-
amide (2). To a solution of 12 (0.480 g, 2.06 mmol) in anhydrous
CH2Cl2 (20 ml) and Et3N (0.624 g, 6.18 mmol) was added acetic
anhydride (0.540 g, 5.29 mmol) at room temperature. The mixture
was stirred for 6 h, then a saturated aqueous solution of NaHCO3
(20 ml) was added. The organic phase was separated and the
aqueous one was washed with CH2Cl2 (2ꢂ10 ml). The combined
organic solutions were dried over MgSO4 and evaporated to dry-
ness. The residue was purified by column chromatography (SiO2;
CH2Cl2/MeOH 95:5) to afford the title compound 2 (0.488 g, 86%) as
a white solid, mp 129e131 ꢀC; nmax(KBr) 3438, 3278, 3087, 1710,
4.1.8. N-(3-((4-(4-(4-(Dibutylamino)styryl)-2,3,5,6-tetrafluorostyryl)
phenyl)(methyl)amino)propyl)acetamide (1). To a solution of 10
(0.150 g, 0.264 mmol) in anhydrous CH2Cl2 (10 ml) and Et3N
(72.6 mg, 0.72 mmol) was added acetic anhydride (54 mg,
0.53 mmol) at room temperature. The mixture was stirred for 4 h,
then a saturated aqueous solution of NaHCO3 (10 ml) was added.
The organic phase was separated and the aqueous one was washed
with CH2Cl2 (2ꢂ5 ml). The combined organic solutions were dried
over MgSO4 and evaporated to dryness. The residue was purified by
column chromatography (SiO2; CH2Cl2/MeOH 98:2) to afford the
title compound 1 (0.210 g, 91%) as an orange solid, mp 181e183 ꢀC;
1620, 1568, 1390, 1282 cmꢁ1
; dH (400 MHz, CDCl3) 1.99 (3H, s,
NCOCH3), 2.04 (2H, quin, J 6.4 Hz, CH2), 2.38 (3H, d, J 1.1 Hz, CH3Ar),
3.46 (2H, q, J 6.4 Hz, CH2), 4.08 (2H, t, J 6.4 Hz, CH2), 5.95 (1H, br s,
NH), 6.11 (1H, d, J 1.1 Hz, ArH), 6.77 (1H, d, J 2.5 Hz, ArH), 6.83 (1H,
dd, J 8.8, 2.5 Hz, ArH), 7.47 (1H, d, J 8.8 Hz, ArH); dC (100.6 MHz,
CDCl3) 18.7, 23.3, 28.9, 37.0, 66.4, 101.5, 112.0, 112.4, 113.7, 125.6,
152.6, 155.2, 161.3, 161.7, 170.4; HRMS (ESI): MNaþ, found
298.10507. C15H17NNaO4 requires 298.10498.
nmax(KBr) 3306, 2954, 2929, 2869, 1599, 1523, 1368, 1189 cmꢁ1
; dH
(400 MHz, CD2Cl2) 0.96 (6H, t, J 7.3 Hz, CH3), 1.35 (4H, sex, J 7.3 Hz,
CH2), 1.53e1.61 (4H, m, CH2), 1.77 (2H, quin, J 7.1 Hz, CH2), 1.91 (3H,
s, NCOCH3), 2.97 (3H, s, NCH3), 3.22e3.32 (6H, m, CH2), 3.40 (2H, t, J
7.1 Hz, CH2), 5.52 (1H, br s, NH), 6.62 (2H, d, J 8.8 Hz, ArH), 6.68 (2H,
d, J 8.8 Hz, ArH), 6.83 (1H, d, J 16.8 Hz, H-styryl) 6.87 (1H, d, J
16.8 Hz, H-styryl), 7.37e7.44 (6H, m, H-styryl, ArH); dC (100.6 MHz,
CD2Cl2) 14.1, 20.7, 23.4, 27.5, 29.8, 37.8, 38.6, 50.4, 51.0, 108.7, 109.5,
111.8, 112.3, 114.7, 115.3, 124.0, 124.9, 128.6, 136.7, 137.0, 143.6, 146.0,
149.1, 150.0. HRMS (ESI): MHþ, found 610.34259. C36H44F4N3O re-
quires 610.34150; MNaþ, found 632.32415. C36H43F4N3NaO requires
632.32345.
4.1.12. Methyl 3,5-bis(3-(4-methyl-2-oxo-2H-chromen-7-yloxy)pro-
pylcarbamoyl)benzoate (13). To a solution of 12 (1.20 g, 5.15 mmol)
and 5-(methoxycarbonyl)trimesic acid (0.384 g, 1.72 mmol) in an-
hydrous DMF (20 ml) was added solid 1H-benzo[d][1,2,3]triazol-1-
ol (0.697 g, 5.15 mmol). The mixture was left stirring at room
temperature under inert atmosphere for 1 h and then a solution of
dicyclohexylcarbodiimide (1.00 g, 4.85 mmol) in anhydrous DMF
(10 ml) was added dropwise. The reaction mixture was left under
stirring at room temperature for 48 h. The solvent was removed
under reduced pressure and the residue was redissolved in CH2Cl2
(150 ml). This solution was washed with H2O (3ꢂ80 ml) and the
organic phase was collected. The residue obtained by evaporation
of the organic solvent under reduced pressure was purified by
4.1.9. 2-(3-(4-Methyl-2-oxo-2H-chromen-7-yloxy)propyl)isoindo-
line-1,3-dione (11). To a solution of 7-hydroxy-4-methyl-2H-chro-
men-2-one (2.0 g, 11.4 mmol) in acetone (130 ml) were added as
solids N-(3-bromopropyl)phthalimide (4.6 g, 17.1 mmol), NaI