Synthesis and crystallographic studies of new acridinic esters and amides: An efficient synthetic route to 4-methyl functionalized acridines

Article abstract of DOI:10.3987/COM-03-9778

In order to open a new way in antitumor drugs research, an efficient synthetic route to mono functional 4-substitued acridine derivatives has been developed on the basis of direct electrophilic substitution of acridine. This method leads to a wide range of simple acridinic patterns that can be linked to various side chains. We present here the synthesis of two new families of acridine ester and amide derivatives, obtained from acridinic alcohol and amine respectively, with high yields. Some crystallographic aspects of one representative compound of each family are discussed.

Full text of DOI:10.3987/COM-03-9778

HETEROCYCLES, Vol. 60, No. 7, 2003, pp. 1653 - 1672
Received, 31st March, 2003, Accepted, 9th May, 2003, Published online, 12th May, 2003
SYNTHESIS AND CRYSTALLOGRAPHIC STUDIES OF NEW
ACRIDINIC ESTERS AND AMIDES: AN EFFICIENT SYNTHETIC
ROUTE TO 4-METHYL FUNCTIONALIZED ACRIDINES
Julien Chiron* and Jean-Pierre Galy
UMR 6009, Laboratoire de Valorisation de la Chimie Fine, case 552, Faculté des
Sciences et Techniques de Saint Jérôme, Avenue de l'Escadrille Normandie
Niemen, 13397 Marseille Cedex 20, France
Fax: +33 (0) 4 91 28 83 23
E-mail: julien.chiron@univ.u-3mrs.fr
Abstract – In order to open a new way in antitumor drugs research, an efficient
synthetic route to mono functional 4-substitued acridine derivatives has been
developed on the basis of direct electrophilic substitution of acridine. This
method leads to a wide range of simple acridinic patterns that can be linked to
various side chains. We present here the synthesis of two new families of acridine
ester and amide derivatives, obtained from acridinic alcohol and amine
respectively, with high yields. Some crystallographic aspects of one
representative compound of each family are discussed.
INTRODUCTION
The constant research in new efficient DNA topoisomerases inhibiting agents is one of the most
important challenge in the development of new antitumor drugs.1 -4 Since the discovery of
N-[2-(dimethylamino)ethyl]acridine-4-carboxamide (DACA) by Denny et al.,5 many research teams have
been working on acridine-4-carboxamide derivatives.6 Indeed, acridine substituents at the position 4 are
known to bind DNA in the major groove7 and the resulting adduct can inhibit topoisomerase I and/or II
action.8 Although important studies have already been published about acridine-4-carboxamide
derivatives, few work has been carried out concerning 4-methyleneacridine derivatives. Such compounds
can bear various side chains and could present comparable biological activities as DACA, that would
open a new promising way for drug discovery. Recent work9 has shown that this methylene position is

able to alkylate DNA after acridine intercalation in order to create a covalently linked drug-DNA adduct,
thus enhancing mutagenic activity.
N
NMe2
O
N
H
Figure 1. N-[2-(Dimethylamino)ethyl]acridine-4-carboxamide (DACA)5
According to these results, we report an efficient synthetic route to acridin-4-ylmethanol in three steps
from acridine using an original synthetic method of acridin-4-ylmethylamine. Both intermediates are
leading precursors to integrate a wide range of functional groups to the acridine scaffold. On that account,
we synthesized two new families of 4-methylacridine derivatives, including various
N-acridin-4-ylmethylamides and O-acridin-4-ylmethyl esters.
RESULTS AND DISCUSSION
Several investigations have been carried out in our laboratory to synthesize methylacridine derivatives on
positions 210and 4.11 In order to increase the DNA binding effect of these derivatives, we decided to
replace aminoalkyl group with carboxamide and carboxyle.
O
8
9
1
7
6
8a
9a
4a
2
3
H2SO4
+
N
HO
N
10a N
O
4
5
O
1'
N
1
2b'
2a'
O
2'
3'
HCl
1-NaNO2
2-H2O
N
N
OH
NH2
2
7
Scheme 1. Synthesis of precursor (1) and intermediates (2) and (7)
The widely used synthetic pathway to amino- or hydroxymethylacridines, involves a minimum of 6 to 7
steps11. Because of such a long synthetic route, the global yield is usually as fairly low as the waste
amount is high. Thanks to the particularity of position 4, electrophilic substitution can easily be achieved
with high regioselectivity depending on the choice of the electrophilic agent. Indeed, nitration is known to

occur preferentially on position 2.12 The commercial availability of simple nonsubstituted acridine drove
us to use such a synthetic pathway.
Figure 2. Crystal structure of compound (1) crystallized from chloroform
In 1971, Hess13 first described a synthesis of acridin-4-yl-methylamine using the Tscherniac-Einorn
reaction, which leads to the intermediate 2-(acridin-4-ylmethyl)isoindole-1,3-dione (1). The
acridin-4-ylmethylamine (2) was then obtained with a overall yield of 61% after acid hydrolysis of the
corresponding phthalimide. Compound (2) must be stored as hydrochloride to avoid rapid degradation.
A crystallographic study of phthalimide (1) has been carried out (Figure 2) that revealed an angle of
84.35(5)° between the planes of the phthalimide and the acridine groups, and an angle of –0.9(3)° for
C11—C10—C9—N1. The molecules are packed along plane (1,0,1) and the acridinic plane is slightly
twisted.
O
X
R
N
N
O
NH2
N
H
R
2
a-k
3a-k
Scheme 2. Synthesis of amides (3a-k)
Compound (2) was allowed to react with a representative family of acids and acyl chlorides (a-k) to give
the corresponding amides (3a-k) as shown in Table 1. The in situ neutralization of hydrochloride of 2
with conc. aqueous NaOH in acetone did not interfere with acylation using acyl chlorides because of the
higher kinetic of amide toward acid formation. The base excess was then used to neutralize the reaction

formed hydrochloride. We did not notice any yield augmentation by using neutral 2 in the reaction.
Compounds (3j-k) were obtained directly from acids derivatives using classic peptide synthesis
methods.14
Table 1. List of R groups and yields of the amide series
Reagent
R
Ph
X
Product Yield %
a
b
c
d
e
f
Cl
Cl
Cl
Cl
Cl
Cl
Cl
Cl
Cl
3a13
3b
3c
3d
3e
3f
73
89
73
77
90
91
94
92
94
92
81
4-Cl-C6H4
4-F-C6H4
4-MeO-C6H4
(Ph)2CH
4-(CH3)2N-C6H4
CH2=CH
g
h
i
3g
3h
3i
4-Cl-Prop
4-(Ph-N=N)-C6H4
j
4-(CH3SO2NH)-2-CH3O-C6H3 OH
(CH3)2N-CH2 OH
3j
k
3k
Figure 3. Crystal structure of compound (3a) crystallized from acetone
Compound (3a) could be crystallized from acetone and a crystallographic study was carried out (Figure 3)
that revealed an angle of 78.39(15)° between acridine and phenyl planes and 19.57(19)° between phenyl
and amide planes. The packing due to H-bond N1a—H1aºO1b occurred along plane (1,1,0).
Afterwards, O-acridin-4-ylmethanol (7) could be obtained from 2 by hydrolyzing the corresponding
diazonium salt according to a classical general method.15

We did notice that the yield is strongly enhanced using 2 as hydrochloride instead of its neutral form.
O
X
R
N
N
O
OH
O
R
7
a-k
8a-k
Scheme 3. Synthesis of esters (8a) to (8k)
Compounds (8a-k) could be synthesized by reacting some of the same acids derivatives (a-k) as above in
Table 1 with alcohol (7) (Table 2). In the case of esters (8a-h) formation, the kinetic of the reaction with
acyl chlorides is lower than for amides formation and needs drastic anhydrous conditions so as to be
completed.
Table 2. Yields of the ester series
Reagent Product Yield Reagent Product Yield
a
b
c
8a
8b
8c
8d
8e
92
90
81
85
79
f
g
h
j
8f
8g
8h
8j
91
84
81
98
73
d
e
k
8k
Figure 4. Crystal structure of compound (8f) crystallized from ethanol
Compound (8f) could be crystallized from ethanol and was studied by X-Ray crystallography (Figure 4).
This analysis showed a particular pi stacking of the acridine groups along the plane (1,0,0) with an

inverted molecule out of three that leads to an elementary pattern containing three molecules. The
molecules self-assemble along plane (0,1,0) thanks to H-bonds O2ºH23B, O4ºH69B and O6ºH46B.
The resulting unit cell contains 12 molecules. The angle formed by phenyl plane and dimethylamino
group vary from 1.0(3)° to 1.9(3)° showing an eclipsed conformation.
Compound (6) was chosen because of its structural similarity with the m-amsa pattern.16 It has been
prepared in three steps from commercially available 4-Aminosalicylic acid with an overall yield of 66%.
Table 3. LogP calculation using various methods through ALOGP 2.1 program17
Compounds ALOGPs IAlogP CLOGP KOWWIN XLOGP
ALOGpS
(mg.L-1)
IAlogS
(mg.L-1)
DACA
2.76
3.08
3.04
3.57
4.21
3.86
3.81
6.59
3.67
2.98
3.82
5.18
2.86
2.76
4.17
4.67
4.27
5.54
8.40
4.41
3.37
4.02
3.42
3.35
3.10
4.69
4.10
5.01
4.45
4.30
5.34
4.46
2.46
3.14
6.33
3.16
2.49
5.21
5.92
5.35
5.38
6.21
5.69
3.84
4.15
4.17
3.18
2.23
3.89
4.24
4.88
4.44
4.32
5.68
4.42
2.69
3.57
6.36
3.51
1.94
4.86
5.51
5.06
4.94
6.75
5.43
3.76
4.64
4.14
2.61
2.74
3.85
4.59
5.22
4.76
4.51
6.07
4.80
3.17
3.83
6.71
3.75
2.40
5.13
5.75
5.29
5.04
6.60
5.33
3.70
4.36
4.28
2.93
-3.88(38.63) -4.52(8.86)
Amsasacrine 4.67
-5.11(3.06)
-5.54(0.90)
-5.93(0.40)
-5.75(0.59)
-5.54(0.98)
-5.30(1.97)
-5.28(1.64)
-6.08(0.29)
-5.97(0.35)
-5.52(1.03)
3a
3b
3c
3d
3e
3f
4.05
4.70
4.28
4.35
5.63
4.34
3.34
3.81
6.32
3.60
2.66
4.96
5.50
4.92
5.00
6.56
5.07
4.30
4.42
3.81
3.07
-6.76(70.63a) -5.29(2.06)
-5.07(3.03)
-4.73(4.89)
-5.07(2.68)
-6.21(0.26)
-5.09(3.57)
-5.31(1.74)
-4.54(7.57)
-5.35(1.40)
-5.65(0.93)
-5.59(1.12)
3g
3h
3i
3j
3k
8a
8b
8c
8d
8e
8f
-3.98(30.50) -4.34(13.41)
-5.76(0.56)
-6.45(0.12)
-5.45(0.46)
-5.77(0.59)
-6.38(0.13)
-7.02(33.21a)
-6.82(50.15a)
-6.29(0.18)
-7.04(37.10a) -7.15(28.56a)
-5.30(1.79)
-4.66(5.70)
-5.52(0.95)
-5.77(0.75)
-5.77(0.61)
-4.77(4.47)
-5.71(0.61)
-6.29(0.22)
8g
8h
8j
8k
-4.13(21.58) -4.40(11.72)
[a] mg.L-1

A comparative LogP calculation of compound (3a-k, 8a-k), DACA and Amsacrine has been performed
(Table 3) using various methods17 that proposes that, compared to DACA, compound (3k) has a lower
LogP and that 3k and 8k have a similar solubility in water. On the other hand, we can see that, compared
to Amsacrine, compounds (3g-h, 3j-k, 8h-k) have a lower LogP and that compounds (3-8g, 3-8k) are
more soluble in water.
CONCLUSION
In conclusion, in this work, we have enhanced a useful synthetic method to functionalize acridine on
position 4 in one step with good yield and we synthesized two precursors of 4-functionalized acridine
derivatives. This method will be developed in order to get a wide variety of mono functionalized acridine
scaffolds. Using both previously cited precursors, we synthesized 11 amides and 10 esters derivatives of
acridine, which will be evaluated in different pharmacological tests. At last, we carried out a
crystallographic study on three acridinic compounds and one benzoic acid, and a comparative LogP
calculation of all esters and all amides derivatives using various methods.
EXPERIMENTAL
General Remarks: All chemicals were used as purchased unless otherwise stated. Column
chromatography was performed on Kieselgel 60. Melting points were performed on a Stuart Scientific
Smp3 apparatus and are uncorrected. NMR spectrum was carried out with Bruker AC 300 (300 MHz for
1H; 75 MHz for 13C). Chemical shifts are given in d relative to the solvent18 : CDCl3 (d1H = 7.28 ppm and
d13C = 77.0 ppm), DMSO-d6 (d1H = 2.48 ppm and d13C = 39.70 ppm) or acetone-d6 (d1H = 2.07 ppm
and d13C = 29.80 ppm). Chemical shift assignments were determined using 1D and 2D experiments
including DEPT,19 gs-COSY,20 gs-HMQC21 and gs-HMBC22 sequences. Chemical shifts of nucleus
marked with the same amount of asterisks could not be differentiated. All crystallographic structures were
solved by use of SIR-92 software23 and refined on F2 with SHELXL-9724 program, measurements were
done with Platon,25 publication picture were prepared with PyMol.26 All crystallographic data can be
obtained free of charge at www.ccdc.cam.ac.uk/conts/retrieving.html [or from the Cambridge
Crystallographic Data Center, 12, Union Road, Cambridge CB2 1EZ, UK; fax: (internat.)
+44-1223/336-033; E-mail: deposit@ccdc.cam.ac.uk]
2-Acridin-4-ylmethylisoindole-1,3-dione (1): A stirred solution of N-(hydroxymethyl)phthalimide (25 g,
0.14 mol) in H2SO4 (150 mL) was cooled to 0°C. Acridine (25 g, 0.14 mol) in H2SO4 (150 mL) was
gradually added and the mixture was allowed to stand at rt under N2 for one week. The reaction mixture
was poured into ice (200 g) and the solution pH was adjusted to 10 with aqueous NH3 (16%). The

precipitate was filtered and the grey solid was thoroughly washed with water. The dried solid was
dissolved in CHCl3 (500 mL) and the solution was filtered. The solution was concentrated under vacuo to
obtain 50 mL and the resulting mixture was allowed to stand overnight at 0°C. The crystallized product
was filtered and recrystallized from CH2Cl2 to give pure 1 as a white crystalline powder (30 g, 64%). mp
199°C (from CH2Cl2). lit.,13 mp 199 - 201°C. 1H NMR (300 MHz, CDCl3, 25°C) : d = 5.75 (s, 2 H, 1'-H),
7.40 (dd, J = 8.3, 7.0 Hz, 1 H, 2-H), 7.48 (dd, J = 7.0, 1.5 Hz, 1 H, 3-H), 7.51 (ddd, J = 8.5, 6.6, 1.0 Hz, 1
H, 7-H), 7.72 (m, 2 H, 3'-H), 7.75 (ddd, J = 8.3, 6.6, 1.1 Hz, 1 H, 6-H), 7.89 (dd, J = 8.3, 1.5 Hz, 1 H,
1-H), 7.89 (m, 2 H, 2'-H), 7.96 (dd, J = 8.5, 1.1 Hz, 1 H, 8-H), 8.22 (dd, J = 8.3, 1.0 Hz, 1 H, 5-H), 8.72 (s,
1 H, 9-H) ppm. 13C NMR (75 MHz, CDCl3, 25°C) : d = 39.02 (C-1'), 123.34 (C-3'), 125.10 (C-2), 125.82
(C-7), 126.42 (C-9a**), 126.51 (C-8a**), 126.98 (C-3), 127.77 (C-8*), 127.94 (C-1*), 130.01 (C-5),
130.01 (C-6), 132.35 (C-2'a), 133.85 (C-4), 133.94 (C-2'), 135.84 (C-9), 146.87 (C-4a), 148.38 (C-10a),
168.43 (C-2'b) ppm. Anal. Calcd for C22H14N2O2: C, 78.09; H, 4.17; N, 8.28. Found: C, 78.21; H, 4.16; N,
8.25.
Crystal Data of 1: Yellow prism crystals (0.4 ¥ 0.3 ¥0.2) of C22H14N2O2, M = 338.35, monoclinic, a =
15.2460(4) Å, b = 14.0620(6) Å, c = 7.7090(7) Å, b = 97.556(3)°, V = 1638.38(17) Å3, Z = 4, space
group: P21/c, rcalcd = 1.372 g cm-3. Data were collected at 293(2) K, Kappa CCD diffractometer, Mo-Ka
radiation, l = 0.71073 Å, j scan method with 90 frames and Dj = 2°, qmax = 26.34°, 3283 measured,
2643 were unique with I>2s(I). R(F) = 0.0623 and wR(F2) = 0.1737 for 3283 reflections, 235 parameters.
Residual electron density: 0.332/-0.419 e/Å3. CCDC-194590 contains the supplementary crystallographic
data for this paper.
C-Acridin-4-ylmethylamine (2): Phthalimide (1) (10 g, 29.55 mmol) was dissolved in 300 mL of HCl
(6N) and the mixture was refluxed for 4 days. The clear yellow solution was cooled with ice and basified
with NH3 (16%). The solution was extracted with CH2Cl2 (3 ¥ 100 mL), the organic phase was washed
with brine, dried with Na2SO4 and the solvent was removed under vacuo to give 2 as a brown oil (5.85 g,
96%, purity > 96% according to NMR data). 2 is used without further purification in the rest of the
present work. 1H NMR (300 MHz, CDCl3, 25°C) : d = 2.45 (s, 2 H, 2'-H), 4.48 (s, 2 H, 1'-H), 7.39 (dd, J
= 8.5, 6.7 Hz, 1 H, 2-H), 7.48 (ddd, J = 8.3, 6.6, 1.1 Hz, 1 H, 7-H), 7.59 (dd, J = 6.7, 1.0 Hz, 1 H, 3-H),
7.72 (ddd, J = 8.4, 6.6, 1.3 Hz, 1 H, 6-H), 7.91 (dd, J = 8.5, 1.0 Hz, 1 H, 1-H), 7.91 (dd, J = 8.3, 1.3 Hz, 1
H, 8-H), 8.19 (dd, J = 8.4, 1.1 Hz, 1 H, 5-H), 8.64 (s, 1 H, 9-H) ppm. 13C NMR (75 MHz, CDCl3, 25°C) :
d = 44.78 (C-1'), 125.47 (C-2), 125.66 (C-7), 126.36 (C-9a), 126.72 (C-8), 127.33 (C-1), 127.78 (C-3*),
127.94 (C-8*), 129.84 (C-5), 129.91 (C-6), 136.01 (C-9), 141.20 (C-4), 147.70 (C-4a), 148.25 (C-10a)
ppm. Anal. Calcd for C14H12N2: C, 80.74; H, 5.81; N, 13.45. Found C, 80.82; H, 5.82; N, 13.49. In order

to preserve its quality, compound (2) was stored as HCl salt: The resulting oil was diluted in 5 mL of
methanol and the solution was poured into dry ether (200 mL). Hydrogen chloride saturated ether was
gradually added until the precipitate turns pale yellow to bright yellow. The mixture was stirred overnight
under dry atmosphere (CaCl2). The hydrochloride of 2 was filtered and washed with dry ether to give a
yellow pulverulent solid (m/z = 209).
N-Acridin-4-ylmethylbenzamide (3a): Hydrochloride of 2 (500 mg, 2.04 mmol) was dispersed into
Me2CO (20 mL) at 0°C and NaOH (5N, 2 mL) was added. A solution of benzoyl chloride (316 mg, 2.24
mmol) in Me2CO (5 mL) was added drop wise and the stirring was maintained for 3 h. The mixture was
poured into cold water (100 mL) and stirred for 1 h. The precipitate was filtered and washed with water.
The resulting solid was recrystallized from C6H12/CHCl3 to give a beige powder (462 mg, 72%). mp
160°C (from C6H12/CHCl3). lit.,13 mp 160 - 163°C. 1H NMR (300 MHz, DMSO-d6, 25°C) : d = 5.29 (d, J
= 5.8 Hz, 2 H, 1'-H), 7.51 (m, 2 H, 4'-H), 7.54 (m, 1 H, 5'-H), 7.57 (dd, J = 8.3, 7.0 Hz, 1 H, 2-H), 7.64
(ddd, J = 8.0, 6.6, 1.0 Hz, 1 H, 7-H), 7.69 (dd, J = 7.0, 1.3 Hz, 1 H, 3-H), 7.88 (ddd, J = 8.4, 6.6, 1.5 Hz, 1
H, 6-H), 7.99 (m, 2 H, 3'-H), 8.07 (dd, J = 8.3, 1.3 Hz, 1 H, 1-H), 8.19 (dd, J = 8.0, 1.5 Hz, 1 H, 8-H),
8.23 (dd, J = 8.4, 1.0 Hz, 1 H, 5-H), 9.13 (s, 1 H, 9-H), 9.13 (t, J = 5.8 Hz, 1 H, 2'-H) ppm. 13C NMR (75
MHz, DMSO-d6, 25°C) : d = 39.71 (C-1'), 125.67 (C-2), 126.10 (C-7), 126.21 (C-9a*), 126.25 (C-8a*),
127.02 (C-3), 127.40 (C-1), 127.49 (C-3'), 128.54 (C-4'), 128.61 (C-8), 129.43 (C-5), 130.76 (C-6),
131.44 (C-5'), 134.67 (C-3'a), 136.69 (C-4), 136.73 (C-9), 146.73 (C-4a), 147.79 (C-10a), 166.75 (C-2'a)
ppm. Anal. Calcd for C21H16N2O: C, 80.75; H, 5.16; N, 8.97. Found: C, 81.01; H, 5.14; N, 8.94.
Crystal Data of 3a: Yellow prism crystals (0.3 ¥ 0.2 ¥ 0.1) of C21H16N2O, M = 312.36, monoclinic, a =
15.6510(5) Å, b = 12.2580(10) Å, c = 8.8150(10) Å, b = 103.157(5)°, V = 1646.8(2) Å3, Z = 4, space
group: P21/c, rcalcd = 1.260 g cm-3. Data were collected at 293(2) K, Kappa CCD diffractometer, Mo-Ka
radiation, l = 0.71073 Å, j scan method with 90 frames and Dj = 2°, qmax = 26.17°, 3128 measured, 2381
were unique with I>2s(I). R(F) = 0.0964 and wR(F2) = 0.1772 for 3128 reflections, 217 parameters.
Residual electron density: 0.161/-0.145 e/Å3. CCDC-194591 contains the supplementary crystallographic
data for this paper.
N-Acridin-4-ylmethyl-4-chlorobenzamide (3b): Same procedure as for 3a with hydrochloride of 2 (567
mg, 2.32 mmol) and 4-chlorobenzoyl chloride (446 mg, 2,56 mmol). 3b was obtained as a beige powder
(705 mg, 88%). mp 102°C (from C6H12/CHCl3). 1H NMR (300 MHz, CDCl3, 25°C) : d = 5.27 (d, J = 5.9
Hz, 2 H, 1'-H), 7.57 (dd, J = 8.4, 6.9 Hz, 1 H, 2-H), 7.58 (m, 2 H, 4'-H), 7.65 (ddd, J = 8.1, 6.7, 1.3 Hz, 1
H, 7-H), 7.69 (dd, J = 6.9, 1.1 Hz, 1 H, 3-H), 7.88 (ddd, J = 8.1, 6.7, 1.5 Hz, 1 H, 6-H), 8.00 (m, 2 H,

3'-H), 8.08 (dd, J = 8.4, 1.1 Hz, 1 H, 1-H), 8.19 (dd, J = 8.1, 1.5 Hz, 1 H, 8-H), 8.23 (dd, J = 8.1, 1.3 Hz,
1 H, 5-H), 9.13 (s, 1 H, 9-H), 9.21 (t, J = 5.9 Hz, 1 H, 2'-H) ppm. 13C NMR (75 MHz, CDCl3, 25°C) : d =
39.60 (C-1'), 125.66 (C-2), 126.11 (C-7), 126.21 (C-9a*), 126.26 (C-8a*), 127.11 (C-3), 127.47 (C-1),
128.62 (C-8), 128.62 (C-3'), 129.46 (C-5), 129.46 (C-4'), 130.77 (C-6), 133.40 (C-3'a), 136.29 (C-4'a),
136.54 (C-4), 136.70 (C-9), 146.70 (C-4a), 147.80 (C-10a), 165.73 (C-2'a) ppm. Anal. Calcd for
C21H15N2OCl: C, 72.73; H, 4.36; N, 8.08. Found: C, 72.85; H, 4.34; N, 8.10.
N-Acridin-4-ylmethyl-4-fluorobenzamide (3c): Same procedure as for 3a with hydrochloride of 2 (500
mg, 2.04 mmol) and 4-fluorobenzoyl chloride (256 mg, 2,24 mmol). 3c was obtained as a brown powder
(483 mg, 72%). mp 138°C (from C6H12/CHCl3). 1H NMR (300 MHz, DMSO-d6, 25°C) : d = 5.26 (d, J =
5.9 Hz, 2 H, 1'-H), 7.33 (m, 2 H, 4'-H), 7.58 (dd, J = 8.3, 6.9 Hz, 1 H, 2-H), 7.64 (ddd, J = 8.0, 6.6, 1.1 Hz,
1 H, 7-H), 7.69 (dd, J = 6.9, 1.3 Hz, 1 H, 3-H), 7.88 (ddd, J = 8.1, 6.6, 1.5 Hz, 1 H, 6-H), 8.05 (m, 2 H,
3'-H), 8.08 (dd, J = 8.3, 1.3 Hz, 1 H, 1-H), 8.19 (dd, J = 8.0, 1.5 Hz, 1 H, 8-H), 8.23 (dd, J = 8.1, 1.1 Hz,
1 H, 5-H), 8.99 (t, J = 5.9 Hz, 1 H, 2'-H), 9.12 (s, 1 H, 9-H) ppm. 13C NMR (75 MHz, DMSO-d6, 25°C) :
d = 39.71 (C-1'), 115.44 (d, J = 22.0 Hz, C-4'), 125.65 (C-2), 126.08 (C-7), 126.20 (C-9a*), 126.25
(C-8a*), 127.06 (C-3), 127.43 (C-1), 128.59 (C-8), 129.43 (C-5), 130.16 (d, J = 9.0 Hz, C-3'), 130.73
(C-6), 131.14 (d, J = 3.0 Hz, C-3'a), 136.65 (C-9), 136.95 (C-4), 146.72 (C-4a), 147.80 (C-10a), 164.12 (d,
J = 248.0 Hz, C-4'a), 165.73 (C-2'a) ppm. Anal. Calcd for C21H15N2OF: C, 76.35; H, 4.58; N, 8.48.
Found: C, 76.28; H, 4.60; N, 8.50.
N-Acridin-4-ylmethyl-4-methoxybenzamide (3d): Same procedure as for 3a with hydrochloride of 2
(500 mg, 2.04 mmol) and 4-methoxybenzoyl chloride (383 mg, 2,24 mmol). 3d was obtained as a beige
powder (531 mg, 76%). mp 146°C (from C6H12/CHCl3). 1H NMR (300 MHz, DMSO-d6, 25°C) : d = 3.82
(s, 3 H, 5'-OMe), 5.26 (d, J = 5.8 Hz, 2 H, 1'-H), 7.04 (m, 2 H, 4'-H), 7.57 (dd, J = 8.3, 6.9 Hz, 1 H, 2-H),
7.64 (ddd, J = 8.1, 6.6, 0.9 Hz, 1 H, 7-H), 7.67 (dd, J = 6.9, 1.4 Hz, 1 H, 3-H), 7.88 (ddd, J = 8.5, 6.6, 1.2
Hz, 1 H, 6-H), 7.97 (m, 2 H, 3'-H), 8.07 (dd, J = 8.3, 1.4 Hz, 1 H, 1-H), 8.19 (dd, J = 8.1, 1.2 Hz, 1 H,
13
8-H), 8.23 (dd, J = 8.5, 0.9 Hz, 1 H, 5-H), 8.99 (t, J = 5.8 Hz, 1 H, 2'-H), 9.12 (s, 1 H, 9-H) ppm. C
NMR (75 MHz, DMSO-d6, 25°C) : d = 39.60 (C-1'), 55.52 (5'-OMe'), 113.74 (C-4'), 125.66 (C-2),
126.08 (C-7), 126.21 (C-9a*), 126.24 (C-8a*), 126.89 (C-3'a), 126.98 (C-3), 127.34 (C-1), 128.61 (C-8),
129.33 (C-3'), 129.44 (C-5), 130.73 (C-6), 136.67 (C-9), 136.95 (C-4), 146.75 (C-4a), 147.78 (C-10a),
161.81(C-4'a), 166.25 (C-2'a) ppm. Anal. Calcd for C 22H18N2O2: C, 77.17; H, 5.30; N, 8.18. Found: C,
77.35; H, 5.29; N, 8.16.

N-Acridin-4-ylmethyl-2,2-diphenylacetamide (3e): Same procedure as for 3a with hydrochloride of 2
(500 mg, 2.04 mmol) and 2,2-diphenylacetyl chloride (471 mg, 2,04 mmol). 3e was obtained as a beige
powder (720 mg, 88%). mp 173°C (from C6H12/CHCl3). 1H NMR (300 MHz, DMSO-d6, 25°C) : d = 5.08
(d, J = 5.7 Hz, 2 H, 1'-H), 5.13 (s, 1 H, 3'-CH), 7.30 (m, 4 H, 4'-H), 7.30 (m, 4 H, 5'-H), 7.30 (m, 2 H,
6'-H), 7.50 (dd, J = 8.3, 6.9 Hz, 1 H, 2-H), 7.57 (dd, J = 6.9, 1.2 Hz, 1 H, 3-H), 7.63 (ddd, J = 8.0, 6.6, 1.1
Hz, 1 H, 7-H), 7.86 (ddd, J = 8.3, 6.6, 1.5 Hz, 1 H, 6-H), 8.06 (dd, J = 8.3, 1.2 Hz, 1 H, 1-H), 8.14 (dd, J
= 8.0, 1.5 Hz, 1 H, 8-H), 8.17 (dd, J = 8.3, 1.1 Hz, 1 H, 5-H), 8.80 (t, J = 5.7 Hz, 1 H, 2'-H), 9.11 (s, 1 H,
13
9-H) ppm. C NMR (75 MHz, DMSO-d6, 25°C) : d = 39.37 (C-1'), 56.78 (3'-CH), 125.53 (C-2), 126.14
(C-7), 126.20 (C-9a*), 126.25 (C-8a*), 126.82 (C-6'), 127.59 (C-1**), 127.71 (C-3**), 128.42 (C-4'),
128.58 (C-8), 128.76 (C-5'), 129.47 (C-5), 130.73 (C-6), 136.55 (C-4), 136.71 (C-9), 140.65 (C-3'a),
146.70 (C-4a), 147.80 (C-10a), 171.45 (C-2'a) ppm. Anal. Calcd for C28H22N2O: C, 83.56; H, 5.51; N,
6.96. Found: C, 83.67; H, 5.49; N, 6.94.
N-Acridin-4-ylmethyl-4-dimethylaminobenzamide (3f): Same procedure as for 3a with hydrochloride
of 2 (508 mg, 2.08 mmol) and 4-dimethylaminobenzoyl chloride (381 mg, 2,08 mmol). 3f was obtained
as a yellow powder (656 mg, 89%). mp 205°C (from C6H12/CHCl3). 1H NMR (300 MHz, DMSO-d6,
25°C) : d = 2.97 (s, 6 H, 5'-NMe2), 5.24 (d, J = 5.9 Hz, 2 H, 1'-H), 6.73 (m, 2 H, 4'-H), 7.57 (dd, J = 8.2,
7.0 Hz, 1 H, 2-H), 7.64 (ddd, J = 8.3, 6.6, 1.1 Hz, 1 H, 7-H), 7.66 (dd, J = 7.0, 1.1 Hz, 1 H, 3-H), 7.85 (m,
2 H, 3'-H), 7.88 (ddd, J = 8.6, 6.6, 1.5 Hz, 1 H, 6-H), 8.06 (dd, J = 8.2, 1.1 Hz, 1 H, 1-H), 8.19 (dd, J =
8.3, 1.5 Hz, 1 H, 8-H), 8.23 (dd, J = 8.6, 1.1 Hz, 1 H, 5-H), 8.77 (t, J = 5.9 Hz, 1 H, 2'-H), 9.13 (s, 1 H,
13
9-H) ppm. C NMR (75 MHz, DMSO-d6, 25°C) : d = 39.47 (C-1'), 39.93 (5'-NMe2), 111.05 (C-4'),
121.32 (C-3'a), 125.69 (C-2), 126.08 (C-7), 126.21 (C-9a*), 126.23 (C-8a*), 126.93 (C-3), 127.24 (C-1),
128.62 (C-8), 128.82 (C-3'), 129.45 (C-5), 130.73 (C-6), 136.67 (C-9), 137.32 (C-4), 146.79 (C-4a),
147.77 (C-10a), 152.35 (C-4'a), 166.63 (C-2'a) ppm. Anal. Calcd for C23H21N3O: C, 77.72; H, 5.96; N,
11.82. Found: C, 77.91; H, 5.94; N, 11.79.
N-Acridin-4-ylmethylacrylamide (3g): Same procedure as for 3a with hydrochloride of 2 (500 mg, 2.04
mmol) and acryloyl chloride (185 mg, 2,04 mmol). 3g was obtained as a beige powder (495 mg, 93%).
mp 179°C (from C6H12/CHCl3). 1H NMR (300 MHz, DMSO-d6, 25°C) : d = 5.13 (d, J = 5.9 Hz, 2 H,
1'-H), 5.64 (dd, J = 10.1, 2.2 Hz, 1 H, 4'-CHcis), 6.16 (dd, J = 17.2, 2.2 Hz, 1 H, 5'-CHtrans), 6.41 (dd, J
= 17.2, 10.1 Hz, 1 H, 3'-CH), 7.58 (dd, J = 8.2, 6.9 Hz, 1 H, 2-H), 7.64 (ddd, J = 8.5, 6.6, 1.0 Hz, 1 H, 7-
H), 7.67 (dd, J = 6.9, 1.5 Hz, 1 H, 3-H), 7.87 (ddd, J = 8.4, 6.6, 1.5 Hz, 1 H, 6-H), 8.08 (dd, J = 8.2, 1.5
Hz, 1 H, 1-H), 8.18 (dd, J = 8.5, 1.5 Hz, 1 H, 8-H), 8.21 (dd, J = 8.4, 1.0 Hz, 1 H, 5-H), 8.68 (t, J = 5.9
13
Hz, 1 H, 2'-H), 9.12 (s, 1 H, 9-H) ppm. C NMR (75 MHz, DMSO-d6, 25°C) : d = 39.05 (C-1'), 125.54

(4'-CH2), 125.65 (C-2), 126.13 (C-7), 126.22 (C-9a*), 126.28 (C-8a*), 127.57 (C-1**), 127.64 (C-3**),
128.61 (C-8), 129.47 (C-5), 130.76 (C-6), 132.00 (3'-CH), 136.51 (C-4), 136.72 (C-9), 146.70 (C-4a),
147.84 (C-10a), 165.15 (C-2'a) ppm. Anal. Calcd for C17H14N2O: C, 77.84; H, 5.38; N, 10.68. Found: C,
77.99; H, 5.36; N, 10.64.
N-Acridin-4-ylmethyl-4-chlorobutyramide (3h): Same procedure as for 3a with hydrochloride of 2
(500 mg, 2.04 mmol) and 4-chlorobutyryl chloride (288 mg, 2,04 mmol). 3h was obtained as a beige
powder (577 mg, 90%). mp 112°C (from C6H12/CHCl3). 1H NMR (300 MHz, DMSO-d6, 25°C) : d = 2.01
(quint, J = 6.9 Hz, 2 H, 4'-CH2), 2.41 (t, J = 6.9 Hz, 2 H, 3'-CH2), 3.98 (t, J = 6.9 Hz, 2 H, 5'-CH2Cl), 5.05
(d, J = 5.9 Hz, 2 H, 1'-H), 7.58 (dd, J = 8.4, 6.9 Hz, 1 H, 2-H), 7.65 (dd, J = 6.9, 1.3 Hz, 1 H, 3-H), 7.65
(ddd, J = 8.1, 6.6, 1.1 Hz, 1 H, 7-H), 7.87 (ddd, J = 8.4, 6.6, 1.4 Hz, 1 H, 6-H), 8.06 (dd, J = 8.4, 1.3 Hz, 1
H, 1-H), 8.17 (dd, J = 8.1, 1.4 Hz, 1 H, 8-H), 8.19 (dd, J = 8.4, 1.1 Hz, 1 H, 5-H), 8.48 (t, J = 5.9 Hz, 1 H,
2'-H), 9.12 (s, 1 H, 9-H) ppm. 13C NMR (75 MHz, DMSO-d6, 25°C) : d = 28.52 (4'-CH2), 32.63 (3'-CH2),
38.98 (C-1'), 45.26 (5'-CH2Cl), 125.64 (C-2), 126.10 (C-7), 126.19 (C-9a*), 126.24 (C-8a*), 127.29 (C-3),
127.48 (C-1), 128.59 (C-8), 129.46 (C-5), 130.71 (C-6), 136.66 (C-9), 136.80 (C-4), 146.70 (C-4a),
147.79 (C-10a), 171.60 (C-2'a) ppm. Anal. Calcd for C18H17N2OCl: C, 69.12; H, 5.48; N, 8.96. Found: C,
69.25; H, 5.46; N, 8.94.
N-Acridin-4-ylmethyl-4-phenylazobenzamide (3i): Same procedure as for 3a with hydrochloride of 2
(500 mg, 2.04 mmol) and 4-phenylazobenzoyl chloride (500 mg, 2,04 mmol). 3i was obtained as an
orange powder (790 mg, 93%). mp 169°C (from C6H12/CHCl3). 1H NMR (300 MHz, DMSO-d6, 25°C) :
d = 5.32 (d, J = 5.8 Hz, 2 H, 1'-H), 7.60 (dd, J = 8.3, 6.9 Hz, 1 H, 2-H), 7.63 (m, 2 H, 6'-H), 7.63 (m, 1 H,
7'-H), 7.74 (dd, J = 6.9, 1.3 Hz, 1 H, 3-H), 8.24 (dd, J = 8.4, 1.0 Hz, 1 H, 5-H), 7.89 (ddd, J = 8.4, 6.6, 1.5
Hz, 1 H, 6-H), 7.65 (ddd, J = 8.3, 6.6, 1.0 Hz, 1 H, 7-H), 8.20 (dd, J = 8.3, 1.5 Hz, 1 H, 8-H), 7.94 (m, 2
H, 5'-H), 8.00 (m, 2 H, 4'-H), 8.09 (dd, J = 8.3, 1.3 Hz, 1 H, 1-H), 8.20 (m, 2 H, 3'-H), 9.15 (s, 1 H, 9-H),
13
9.33 (t, J = 5.8 Hz, 1 H, 2'-H) ppm. C NMR (75 MHz, DMSO-d6, 25°C) : d = 39.79 (C-1'), 122.64
(C-5'), 122.94 (C-4'), 125.70 (C-2), 126.23 (C-9a*), 147.82 (C-10a), 129.45 (C-5), 130.79 (C-6), 126.13
(C-7), 128.64 (C-8), 126.28 (C-8a*), 127.15 (C-3), 127.50 (C-1), 128.87 (C-6'), 129.74 (C-3'), 132.20
(C-7'), 136.54 (C-3'a), 136.74 (C-9), 136.83 (C-4), 146.73 (C-4a), 152.10 (C-5'a), 153.53 (C-4'a), 166.01
(C-2'a) ppm. Anal. Calcd for C27H20N4O: C, 77.87; H, 4.84; N, 13.45. Found: C, 77.65; H, 4.85; N, 13.47.
N-Acridin-4-ylmethyl-4-methanesulfonylamino-2-methoxybenzamide (3j). Hydrochloride of 2 (500
mg, 2.04 mmol) was treated with Et3N (1 mL, 7.19 mmol) in Me2CO (5 mL) and the mixture was added
to a solution of acid (6) (551 mg, 2,25 mmol), HOBt (304 mg, 2,25 mmol) and DCC (464 mg, 2,25

mmol) in Me2CO (10 mL). The mixture was stirred at rt under dry atmosphere (CaCl2) for 72 h. The
solvent was removed under vacuo and the dry residue was treated with NaOH (1N, 50 mL). The
precipitated DCU was filtered off and washed with water, the solution was acidified with 6N HCl to pH 2
in ice bath and basified to pH 8 with 1N NaOH. The resulting precipitate was filtered off and washed with
1
water to give 3j as a yellow solid (808 mg, 91%). mp 218°C (from C6H12/CHCl3). H NMR (300 MHz,
CDCl3, 25°C) : d = 2.97 (s, 3 H, 8'-SO2Me), 3.66 (s, 3 H, 6'-OMe), 5.33 (d, J = 6.0 Hz, 2 H, 1'-H), 6.74
(dd, J = 8.5, 1.9 Hz, 1 H, 4'-H), 6.86 (d, J = 1.9 Hz, 1 H, 5'-H), 7.47 (dd, J = 8.4, 6.8 Hz, 1 H, 2-H), 7.56
(ddd, J = 8.3, 6.6, 1.1 Hz, 1 H, 7-H), 7.81 (ddd, J = 8.6, 6.6, 1.3 Hz, 1 H, 6-H), 7.85 (dd, J = 6.8, 0.9 Hz, 1
H, 3-H), 7.93 (dd, J = 8.4, 0.9 Hz, 1 H, 1-H), 8.02 (dd, J = 8.3, 1.3 Hz, 1 H, 8-H), 8.18 (d, J = 8.5 Hz, 1 H,
13
3'-H), 8.28 (dd, J = 8.6, 1.1 Hz, 1 H, 5-H), 8.77 (s, 1 H, 9-H), 9.23 (t, J = 6.0 Hz, 1 H, 2'-H) ppm. C
NMR (75 MHz, CDCl3, 25°C) : d = 39.53 (6'-OMe), 41.53 (C-1'), 55.96 (8'-SO2Me), 102.38 (C-5'),
111.61 (C-4'), 118.47 (C-3'a), 125.75 (C-2**), 125.79 (C-7**), 126.52 (C-9a*), 126.80 (C-8a*), 127.94
(C-3), 128.30 (C-1), 129.57 (C-8), 129.75 (C-5), 130.22 (C-6), 133.85 (C-3'), 136.29 (C-9), 136.38 (C-4),
140.77 (C-4'a), 148.02 (C-4a), 148.29 (C-10a), 158.67 (C-5'a), 164.25 (C-2'a) ppm. Anal. Calcd for
C23H21N3O4S: C, 63.43; H, 4.86; N, 9.65. Found: C, 63.22; H, 4.87; N, 9.68.
N-Acridin-4-ylmethyl-2-dimethylaminoacetamide (3k): Hydrochloride of 2 (500 mg, 2.04 mmol) was
dissolved in water (1 mL), basified with NH3 (16%) and extracted with CH2Cl2 (3 ¥ 5 mL). The organic
layer was dried with Na2SO4 and reduced to 5 mL under vacuo. A solution of HOBt (304 mg, 2.25 mmol),
Et3N (0.2 mL, 1.44 mmol) and N,N-dimethylglycine hydrochloride (314 mg, 2.25 mmol) in CH2Cl2 (2
mL) was added at once and the mixture was maintained under dry atmosphere (CaCl2). DCC (506 mg,
2.45 mmol) and triethylamine (0.5 mL, 3.60 mmol) are added after 10 min. The stirring was maintained
for 48 h, the mixture was then diluted with EtOAc (20 mL) and filtered. The organic layer was washed
with NaOH (1N, 10 mL) and brine (10 mL) and dried with Na2SO4. The resulting oil was purified by
column chromatography (CH2Cl2 /EtOH, 9:1, v/v) to give pure 3k as brown oil (482 mg, 80%). 1H NMR
(300 MHz, CDCl3, 25°C) : d = 2.16 (s, 6 H, 4'-NMe2), 2.95 (s, 2 H, 3'-CH2), 5.14 (d, J = 6.2 Hz, 2 H, 1'-
H), 7.44 (dd, J = 8.5, 6.8 Hz, 1 H, 2-H), 7.53 (ddd, J = 8.5, 6.6, 1.0 Hz, 1 H, 7-H), 7.74 (dd, J = 6.8, 1.5
Hz, 1 H, 3-H), 7.77 (ddd, J = 8.3, 6.6, 1.3 Hz, 1 H, 6-H), 7.90 (dd, J = 8.5, 1.5 Hz, 1 H, 1-H), 7.97 (dd, J
= 8.5, 1.3 Hz, 1 H, 8-H), 8.22 (dd, J = 8.3, 1.0 Hz, 1 H, 5-H), 8.62 (t, J = 6.2 Hz, 1 H, 2'-H), 8.73 (s, 1 H,
9-H) ppm. 13C NMR (75 MHz, CDCl3, 25°C) : d = 40.92 (C-1'), 45.89 (4'-NMe2), 63.28 (3'-CH2), 125.48
(C-2), 125.78 (C-7), 126.40 (C-9a*), 126.65 (C-8a*), 127.88 (C-1**), 128.04 (C-8**), 129.32 (C-3),
129.67 (C-5), 130.13 (C-6), 135.99 (C-4), 136.15 (C-9), 147.75 (C-4a), 148.28 (C-10a), 170.46 (C-2'a)
ppm. Anal. Calcd for C18H19N3O: C, 73.69; H, 6.53; N, 14.32. Found: C, 73.55; H, 6.52; N, 14.28.

4-Amino-2-methoxybenzoic acid methyl ester (4): According to a previously reported procedure,27
4-aminosalycilic acid (10.00 g, 63.30 mmol) was dissolved in dry Me2CO (200 mL) and KOH pellets are
added (9.20 g, 163.96 mmol). To the vigorously stirred mixture at 25°C, Me2SO4 (14.7 mL, 154.60
mmol) was added drop wise in 1 h and the stirring was maintained for 3 h. The solvent was then removed,
the residual solid was dissolved in hot water and the pH was adjusted to 9 with 1N NaOH. After cooling,
the precipitate was filtered off and thoroughly washed with water. The dry crude solid was dispersed in
EtOAc (50 mL) and the mixture was cooled overnight to 0°C. The precipitate was filtered off and washed
with few cold EtOAc to give 4 as a white powder (8.76 g, 74%). mp 155°C (from EtOAc). lit.,27 mp
153-155°C.
4-Methanesulfonylamino-2-methoxybenzoic acid methyl ester (5): Ester (4) (4.00 g, 22.08 mmol) and
pyridine (4.5 mL, 55.64 mmol) were dissolved in anhydrous CHCl3 (80 mL) at 0°C under N2. A solution
of mesyl chloride (4.3 mL, 55.56 mmol) in dry CHCl3 (25 mL) was added drop wise in 30 min. The
solution was stirred for 5 h and the solvent was removed under vacuo. The crude pink oil was dissolved in
few mL of Me2CO and poured into water (150 mL). The precipitate was filtered off and washed with
water. The solid was then recrystallized from EtOH to give pure 5 as a white powder (5.24 g, 95%). mp
1
152°C (from EtOH). H NMR (300 MHz, CDCl3, 25°C) : d = 3.06 (s, 3 H, 7- SO2Me), 3.85 (s, 3 H,
6-OMe), 3.87 (s, 3 H, 5-CO2Me), 6.75 (dd, J = 8.5, 2.1 Hz, 1 H, 1-H), 6.88 (d, J = 2.1 Hz, 1 H, 3-H), 7.18
13
(s, 1 H, 4-H), 7.80 (d, J = 8.5 Hz, 1 H, 2-H) ppm. C NMR (75 MHz, CDCl3, 25°C) : d = 39.72 (7-
SO2Me), 52.06 (5-CO2Me), 56.12 (6-OMe), 102.48 (C-3), 110.06 (C-1), 115.86 (C-2a), 133.61 (C-2),
142.00 (C-1a), 160.76 (C-3a), 165.87 (2b-CO2Me) ppm. Anal. Calcd for C10H13NO5S: C, 46.32; H, 5.05;
N, 5.40. Found: C, 46.41; H, 5.03; N, 5.39.
4-Methanesulfonylamino-2-methoxybenzoic acid (6): Ester (5) (5.00 g, 20.39 mmol) was dissolved in
THF (100 mL). A solution of LiOH (4.05 g, 96.52 mmol) in water (100 mL) was added in one portion.
The mixture was stirred overnight. THF was removed and the pH was adjusted to 1 with 6N HCl. The
precipitate was filtered off and washed with water. After recrystallization from EtOH, pure 6 was
1
obtained as a white powder (4.30 g, 91%). mp 182°C (from EtOH). H NMR (300 MHz, acetone-d6,
25°C) : d = 3.06 (s, 3 H, 7-SO2Me), 4.02 (s, 3 H, 6-OMe), 7.02 (dd, J = 8.5, 2.1 Hz, 1 H, 1-H), 7.17 (d, J
= 2.1 Hz, 1 H, 3-H), 7.93 (d, J = 8.5 Hz, 1 H, 2-H), 9.06 (s, 1 H, 4-NH), 10.73 (s, 1 H, 5-CO2H) ppm. 13C
NMR (75 MHz, acetone-d6, 25°C) : d = 40.01 (7-SO2Me), 56.71 (6-OMe), 102.86 (C-3), 111.34 (C-1),
114.84 (C-2a), 134.74 (C-2), 145.14 (C-1a), 160.84 (C-3a), 165.77 (2b-CO2H) ppm. Anal. Calcd for
C9H11NO5S: C, 44.08; H, 4.52; N, 5.71. Found: C, 44.20; H, 4.51; N, 5.69.

Acridin-4-ylmethanol (7): According to a previously reported procedure,15 a solution of NaNO2 (2.54 g,
36.81 mmol) in water (20 mL) was added drop wise to an ice cooled solution of hydrochloride of 2 (3.00
g, 12.26 mmol) in aqueous AcOH (100 mL, 50%). The mixture was stirred overnight at rt, basified with a
solution of 5N NaOH and extracted with CH2Cl2 (3 ¥ 100 mL). The solvent was reduced to 50 mL under
vacuo and a solution of KOH (15 mL, 5% in methanol) was added. The mixture was stirred overnight at
rt, washed with brine (2 ¥ 20 mL), dried with MgSO4. After evaporation of the solvent under vacuo, the
resulting solid was purified by column chromatography (CH2Cl2 / EtOAc, 9:1, v/v) to give pure 7 as a
yellow powder (2.33 g, 91%). mp 99.3°C. 1H NMR (300 MHz, CDCl3, 25°C) : d = 5.29 (s, 2 H, 1'-H),
5.66 (s, 1 H, 2'-H), 7.46 (dd, J = 8.4, 6.8 Hz, 1 H, 2-H), 7.56 (ddd, J = 8.4, 6.6, 1.2 Hz, 1 H, 7-H), 7.62 (br
dd, J = 6.8 Hz, 1 H, 3-H), 7.79 (ddd, J = 8.3, 6.6, 1.1 Hz, 1 H, 6-H), 7.93 (br dd, J = 8.4 Hz, 1 H, 1-H),
8.00 (dd, J = 8.4, 1.1 Hz, 1 H, 8-H), 8.20 (dd, J = 8.3, 1.2 Hz, 1 H, 5-H), 8.80 (s, 1 H, 9-H) ppm. 13C
NMR (75 MHz, CDCl3, 25°C) : d = 65.10 (C-1'), 125.28 (C-2), 125.78 (C-7), 126.29 (C-9a), 126.55
(C-8a), 127.66 (C-3), 127.97 (C-8*), 128.01 (C-1*), 129.15 (C-5), 130.38 (C-6), 136.59 (C-9), 137.59
(C-4), 147.48 (C-4a), 148.00 (C-10a) ppm. Anal. Calcd for C14H11NO: C, 80.36; H, 5.30; N, 6.69. Found:
C, 80.48; H, 5.18; N, 6.67.
Acridin-4-ylmethyl benzoate (8a): A solution of 4-chlorobenzoyl chloride (460 mg, 2.63 mmol) in
Me2CO (5 mL) was added drop wise to a solution of alcohol (7) (500 mg, 2,39 mmol) and Et3N (0.5 mL,
3.60 mmol) in Me2CO (15 mL) at 0°C under dry atmosphere (CaCl2). The stirring was maintained for
about 6 h (TLC control, CH2Cl2/EtOAc, 9:1, v/v) and the mixture was poured into cold water (50 mL).
The precipitate was filtered off and washed with water. The dry solid was dissolved in CHCl3 (10 mL),
the solution was filtered and the solvent was removed. The crude solid was recrystallized from MeOH to
1
give pure 8a as a beige powder (758 mg, 92%). mp 129°C (from MeOH). H NMR (300 MHz, CDCl3,
25°C) : d = 6.29 (s, 2 H, 1'-H), 7.46 (m, 2 H, 3'-H), 7.53 (dd, J = 8.4, 6.8 Hz, 1 H, 2-H), 7.55 (ddd, J = 8.5,
6.6, 1.1 Hz, 1 H, 7-H), 7.57 (m, 1 H, 4'-H), 7.76 (ddd, J = 8.4, 6.6, 1.4 Hz, 1 H, 6-H), 7.87 (dd, J = 6.8,
1.1 Hz, 1 H, 3-H), 7.97 (dd, J = 8.4, 1.1 Hz, 1 H, 1-H), 8.00 (dd, J = 8.5, 1.4 Hz, 1 H, 8-H), 8.18 (m, 2 H,
2'-H), 8.26 (dd, J = 8.4, 1.1 Hz, 1 H, 5-H), 8.72 (s, 1 H, 9-H) ppm. 13C NMR (75 MHz, CDCl3, 25°C) : d
= 63.58 (C-1'), 125.15 (C-2), 125.79 (C-7), 126.73 (C-9a), 127.00 (C-8a), 127.68 (C-3), 127.94 (C-8),
128.02 (C-1), 128.35 (C-3'), 129.73 (C-2'), 129.96 (C-5), 130.06 (C-6), 130.46 (C-2a'), 132.89 (C-4'),
134.41 (C-4), 135.80 (C-9), 146.73 (C-4a), 148.48 (C-10a), 166.60 (C-2b') ppm. Anal. Calcd for
C21H15NO2: C, 80.49; H, 4.82; N, 4.47. Found: C, 80.55; H, 4.81; N, 4.46.
Acridin-4-ylmethyl 4-chlorobenzoate (8b): Same procedure as for 8a with alcohol (7) (500 mg, 2,39
mmol) and 4-chlorobenzoyl chloride (460 mg, 2.63 mmol). 8b was obtained as a beige powder (348 mg,

90%). mp 125°C (from MeOH). 1H NMR (300 MHz, CDCl3, 25°C) : d = 6.25 (s, 2 H, 1'-H), 7.40 (m, 2 H,
3'-H), 7.51 (dd, J = 8.3, 6.8 Hz, 1 H, 2-H), 7.53 (ddd, J = 8.0, 6.6, 1.0 Hz, 1 H, 7-H), 7.76 (ddd, J = 8.4,
6.6, 1.4 Hz, 1 H, 6-H), 7.84 (dd, J = 6.8, 1.0 Hz, 1 H, 3-H), 7.95 (dd, J = 8.3, 1.0 Hz, 1 H, 1-H), 7.98 (dd,
J = 8.0, 1.4 Hz, 1 H, 8-H), 8.07 (m, 2 H, 2'-H), 8.23 (dd, J = 8.4, 1.0 Hz, 1 H, 5-H), 8.74 (s, 1 H, 9-H)
13
ppm. C NMR (75 MHz, CDCl3, 25°C) : d = 63.84 (C-1'), 125.14 (C-2), 125.88 (C-7), 126.27 (C-9a),
126.55 (C-8a), 127.97 (C-3), 127.97 (C-8), 128.26 (C-1), 128.70 (C-3'), 128.94 (C-2a'), 129.99 (C-5*),
130.15 (C-6*), 131.14 (C-2'), 134.21 (C-4), 135.87 (C-9), 139.33 (C-3a'), 146.79 (C-4a), 148.55 (C-10a),
165.78 (C-2b') ppm. Anal. Calcd for C21H14NO2Cl: C, 72.52; H, 4.06; N, 4.03. Found: C, 72.70; H, 4.05;
N, 4.02.
Acridin-4-ylmethyl 4-fluorobenzoate (8c): Same procedure as for 8a with alcohol (7) (500 mg, 2,39
mmol) and 4-fluorobenzoyl chloride (417 mg, 2.63 mmol). 8c was obtained as a beige powder (670 mg,
81%). mp 114°C (from MeOH). 1H NMR (300 MHz, CDCl3, 25°C) : d = 6.26 (s, 2 H, 1'-H), 7.10 (m, 2 H,
3'-H), 7.51 (dd, J = 8.4, 6.8 Hz, 1 H, 2-H), 7.53 (ddd, J = 7.7, 6.6, 1.0 Hz, 1 H, 7-H), 7.77 (ddd, J = 8.4,
6.6, 1.3 Hz, 1 H, 6-H), 7.85 (dd, J = 6.8, 1.1 Hz, 1 H, 3-H), 7.96 (dd, J = 8.4, 1.1 Hz, 1 H, 1-H), 7.99 (dd,
J = 7.7, 1.3 Hz, 1 H, 8-H), 8.16 (m, 2 H, 2'-H), 8.24 (dd, J = 8.4, 1.0 Hz, 1 H, 5-H), 8.75 (s, 1 H, 9-H)
ppm. 13C NMR (75 MHz, CDCl3, 25°C) : d = 63.71 (C-1'), 115.47 (d, J = 21.0 Hz, C-3'), 125.12 (C-2),
125.85 (C-7), 126.24 (C-9a), 126.52 (C-8a), 126.72 (d, J = 3.0 Hz, C-2a'), 127.88 (C-3**), 127.95
(C-8**), 128.18 (C-1**), 129.97 (C-5*), 130.10 (C-6*), 132.26 (d, J = 9.0 Hz, C-2'), 134.28 (C-4),
135.83 (C-9), 146.77 (C-4a), 148.52 (C-10a), 165.73 (d, J = 254.0 Hz, C-3a'), 166.65 (C-2b') ppm. Anal.
Calcd for C21H14NO2F: C, 76.12; H, 4.26; N, 4.23. Found: C, 76.28; H, 4.25; N, 4.22.
Acridin-4-ylmethyl 4-methoxybenzoate (8d): Same procedure as for 8a with alcohol (7) (500 mg, 2,39
mmol) and 4-methoxybenzoyl chloride (449 mg, 2.63 mmol). 8d was obtained as a beige powder (698
mg, 85%). mp 132°C (from MeOH). 1H NMR (300 MHz, CDCl3, 25°C) : d = 3.85 (s, 3 H, 4'-OMe), 6.25
(s, 2 H, 1'-H), 6.92 (m, 2 H, 3'-H), 7.51 (dd, J = 8.3, 6.8 Hz, 1 H, 2-H), 7.53 (ddd, J = 8.0, 6.6, 1.0 Hz, 1 H,
7-H), 7.76 (ddd, J = 8.4, 6.6, 1.4 Hz, 1 H, 6-H), 7.86 (dd, J = 6.8, 1.1 Hz, 1 H, 3-H), 7.95 (dd, J = 8.3, 1.1
Hz, 1 H, 1-H), 7.99 (dd, J = 8.0, 1.4 Hz, 1 H, 8-H), 8.11 (m, 2 H, 2'-H), 8.25 (dd, J = 8.4, 1.0 Hz, 1 H,
13
5-H), 8.75 (s, 1 H, 9-H) ppm. C NMR (75 MHz, CDCl3, 25°C) : d = 55.40 (4'-OMe), 63.29 (C-1'),
113.62 (C-3'), 122.92 (C-2'a), 125.22 (C-2), 125.82 (C-7), 126.27 (C-9a), 126.54 (C-8a), 127.61 (C-3),
127.95 (C-8**), 127.97 (C-1**), 130.03 (C-5*), 130.07 (C-6*), 131.78 (C-2'), 134.73 (C-4), 135.83 (C-9),
146.82 (C-4a), 148.52 (C-10a), 163.35 (C-3'a), 166.37 (C-2'b) ppm. Anal. Calcd for C22H17NO3: C, 76.95;
H, 4.99; N, 4.08. Found: C, 77.24; H, 4.97; N, 4.07.

Acridin-4-ylmethyl 2,2-diphenylacetate (8e): Same procedure as for 8a with alcohol (7) (500 mg, 2,39
mmol) and 2,2-diphenylacetyl chloride (606 mg, 2.63 mmol). 8e was obtained as a white powder (765 mg,
79%). mp 117°C (from MeOH). 1H NMR (300 MHz, CDCl3, 25°C) : d = 5.17 (s, 1 H, 2'-CH), 6.08 (s, 2
H, 1'-H), 7.40 (dd, J = 8.3, 6.8 Hz, 1 H, 2-H), 7.52 (ddd, J = 8.0, 6.6, 0.8 Hz, 1 H, 7-H), 7.58 (dd, J = 6.8,
1.1 Hz, 1 H, 3-H), 7.75 (ddd, J = 8.3, 6.6, 1.2 Hz, 1 H, 6-H), 7.92 (dd, J = 8.3, 1.1 Hz, 1 H, 1-H), 7.98 (dd,
J = 8.0, 1.2 Hz, 1 H, 8-H), 8.18 (dd, J = 8.3, 0.8 Hz, 1 H, 5-H), 8.72 (s, 1 H, 9-H), 7.26-7.35 (m, 4 H,
3'-H), 7.26-7.35 (m, 4 H, 4'-H), 7.26-7.35 (m, 2 H, 5'-H) ppm. 13C NMR (75 MHz, CDCl3, 25°C) : d =
57.27 (2'-CH), 63.88 (C-1'), 125.06 (C-2), 125.79 (C-7), 126.19 (C-9a), 126.48 (C-8a), 127.18 (C-5'),
127.92 (C-3), 128.17 (C-8**), 128.22 (C-1**), 128.51 (C-3'), 128.75 (C-4'), 129.99 (C-5*), 130.03
(C-6*), 134.03 (C-4), 135.77 (C-9), 138.77 (C-3a'), 146.73 (C-4a), 148.45 (C-10a), 172.38 (C-2a') ppm.
Anal. Calcd for C28H21NO2: C, 83.35; H, 5.25; N, 3.47. Found: C, 83.15; H, 5.26; N, 3.47.
Acridin-4-ylmethyl 4-Dimethylaminobenzoate (8f): Same procedure as for 8a with alcohol (7) (500 mg,
2,39 mmol) and 4-dimethylaminobenzoyl chloride (483 mg, 2.63 mmol). 8f was obtained as a yellow
1
powder (775 mg, 91%). mp 187°C (from MeOH). H NMR (300 MHz, CDCl3, 25°C) : d = 3.01 (s, 6 H,
4'-NMe2), 6.24 (s, 2 H, 1'-H), 6.65 (m, 2 H, 3'-H), 7.48 (dd, J = 8.3, 6.9 Hz, 1 H, 2-H), 7.51 (ddd, J = 8.5,
6.6, 1.0 Hz, 1 H, 7-H), 7.75 (ddd, J = 8.5, 6.6, 1.5 Hz, 1 H, 6-H), 7.86 (dd, J = 6.9, 1.2 Hz, 1 H, 3-H), 7.90
(dd, J = 8.3, 1.2 Hz, 1 H, 1-H), 7.96 (dd, J = 8.5, 1.5 Hz, 1 H, 8-H), 8.05 (m, 2 H, 2'-H), 8.25 (dd, J = 8.5,
13
1.0 Hz, 1 H, 5-H), 8.70 (s, 1 H, 9-H) ppm. C NMR (75 MHz, CDCl3, 25°C) : d = 40.01 (4'-NMe2),
62.76 (C-1'), 110.70 (C-3'), 117.20 (C-2a'), 125.26 (C-2), 125.72 (C-7), 126.22 (C-9a), 126.47 (C-8a),
127.22 (C-3), 127.62 (C-8), 127.94 (C-1), 129.95 (C-5), 130.02 (C-6), 131.45 (C-2'), 135.20 (C-4),
135.74 (C-9), 146.79 (C-4a), 148.43 (C-10a), 153.31 (C-3a'), 166.92 (C-2b') ppm. Anal. Calcd for
C23H20N2O2: C, 77.51; H, 5.66; N, 7.86. Found: C, 77.72; H, 5.64; N, 7.84.
Crystal Data of 8f: Yellow prism crystals (0.4 ¥ 0.3 ¥ 0.05) of C69H60N6O6, M = 1069.23, monoclinic, a
= 23.1280(7) Å, b = 13.1660(7) Å, c = 21.099(1) Å, b = 122.839(2)°, V = 5398.0(4) Å3, Z = 4, space
group: Cc, rcalcd = 1.316 g cm-3. Data were collected at 293(2) K, Kappa CCD diffractometer, Mo-Ka
radiation, l = 0.71073 Å, j scan method with 90 frames and Dj = 2°, qmax = 26.37°, 5236 measured, 4062
were unique with I>2s(I). R(F) = 0.0525 and wR(F2) = 0.1683 for 5236 reflections, 730 parameters.
Residual electron density: 0.188/-0.197 e/Å3. CCDC-194592 contains the supplementary crystallographic
data for this paper.
Acridin-4-ylmethyl acrylate (8g): A solution of acryloyl chloride (460 mg, 2.63 mmol) in Me2CO (5
mL) was added drop wise to a solution of alcohol (7) (500 mg, 2,39 mmol) and Et3N (0.5 mL, 3.60

mmol) in Me2CO (15 mL) at 0°C under dry atmosphere (CaCl2). The stirring was maintained for about 6
h (TLC control, CH2Cl2/EtOAc, 9:1, v/v) and the mixture was poured into cold water (50 mL). The
resulting oil was extracted with CH2Cl2 (3 ¥ 20 mL), dried with Na2SO4 and purified by column
chromatography (CH2Cl2/EtOAc, 9:1, v/v) to give pure 8g as a yellow solid (527 mg, 84%). mp 75°C. 1H
NMR (300 MHz, CDCl3, 25°C) : d = 5.87 (dd, J = 10.4, 1.5 Hz, 1 H, 3'-CHcis), 6.11 (s, 2 H, 1'-H), 6.27
(dd, J = 17.4, 10.4 Hz, 1 H, 2'-CH), 6.52 (dd, J = 17.4, 1.5 Hz, 1 H, 4'-CHtrans), 7.50 (dd, J = 8.3, 6.9 Hz,
1 H, 2-H), 7.52 (ddd, J = 7.9, 6.5, 1.3 Hz, 1 H, 7-H), 7.76 (ddd, J = 8.4, 6.5, 1.1 Hz, 1 H, 6-H), 7.79 (dd, J
= 6.9, 1.3 Hz, 1 H, 3-H), 7.94 (dd, J = 8.3, 1.3 Hz, 1 H, 1-H), 7.98 (dd, J = 7.9, 1.1 Hz, 1 H, 8-H), 8.24
(dd, J = 8.4, 1.3 Hz, 1 H, 5-H), 8.73 (s, 1 H, 9-H) ppm. 13C NMR (75 MHz, CDCl3, 25°C) : d = 63.17
(C-1'), 125.18 (C-2), 125.86 (C-7), 126.27 (C-9a), 126.55 (C-8a), 127.97 (C-8), 128.01 (C-3), 128.16
(C-1*), 128.61 (2'-CH), 130.02 (C-5), 130.11 (C-6), 130.92 (3'-CH2), 134.25 (C-4), 135.86 (C-9), 146.80
(C-4a), 148.54 (C-10a), 166.28 (C-2a') ppm. Anal. Calcd for C17H13NO2: C, 77.55; H, 4.98; N, 5.32.
Found: C, 77.69; H, 4.97; N, 5.31.
Acridin-4-ylmethyl 4-chlorobutyrate (8h): A solution of 4-chlorobutyryl chloride (371 mg, 2.63 mmol)
in Me2CO (5 mL) was added drop wise to a solution of alcohol (7) (500 mg, 2,39 mmol) and Et3N (0.5
mL, 3.60 mmol) in Me2CO (15 mL) at 0°C under dry atmosphere (CaCl2). The stirring was maintained
for about 6 h (TLC control, CH2Cl2) and the mixture was poured into cold water (50 mL). The resulting
oil was extracted with EtOAc (3 ¥ 25 mL), washed with brine, dried with Na2SO4 and purified by column
chromatography (CH2Cl2) to give pure 8h as a brown oil (604 mg, 81%). 1H NMR (300 MHz, CDCl3,
25°C) : d = 2.16 (quint., J = 6.8 Hz, 2 H, 3'-CH2), 2.64 (t, J = 6.8 Hz, 2 H, 2'- CH2), 3.63 (t, J = 6.8 Hz, 2
H, 4'- CH2Cl), 6.01 (s, 2 H, 1'-H), 7.48 (dd, J = 8.4, 7.0 Hz, 1 H, 2-H), 7.51 (ddd, J = 8.5, 6.6, 0.8 Hz, 1 H,
7-H), 7.75 (ddd, J = 8.7, 6.6, 1.3 Hz, 1 H, 6-H), 7.76 (dd, J = 7.0, 0.8 Hz, 1 H, 3-H), 7.92 (dd, J = 8.4, 0.8
Hz, 1 H, 1-H), 7.95 (dd, J = 8.5, 1.3 Hz, 1 H, 8-H), 8.22 (dd, J = 8.7, 0.8 Hz, 1 H, 5-H), 8.70 (s, 1 H, 9-H)
ppm. 13C NMR (75 MHz, CDCl3, 25°C) : d = 27.75 (3'- CH2), 31.38 (2'- CH2), 44.10 (4'- CH2Cl), 63.30
(C-1'), 125.09 (C-2), 125.83 (C-7), 126.23 (C-9a), 126.50 (C-8a), 127.94 (C-3), 128.29 (C-1), 128.29
(C-8), 129.93 (C-5*), 130.11 (C-6*), 134.10 (C-4), 135.84 (C-9), 146.77 (C-4a), 148.51 (C-10a), 172.63
(C-2a') ppm. Anal. Calcd for C18H16NO2Cl: C, 68.90; H, 5.14; N, 4.46. Found: C, 68.99; H, 5.13; N, 4.47.
Acridin-4-ylmethyl 4-methanesulfonylamino-2-methoxybenzoate (8j): A solution of alcohol (7) (500
mg, 2.39 mmol), acid (6) (645 mg, 2.63), DMAP (321 mg, 2.63) and DCC (542 mg, 2.63) in Me2CO (10
mL) was stirred for 72 h at rt under dry atmosphere (CaCl2). Me2CO (50 mL) was then added and the
precipitated DCU was filtered off. The solvent was reduced under vacuo to 5 mL and the mixture was
poured into cold water (50 mL). pH was adjusted to 2 with 1N HCl and then to 9 with 1N NaOH. The

precipitate was filtered off and washed with cold water. The resulting solid was recrystallized from
1
MeOH to give pure 8j as a yellow powder (989 mg, 95%). mp 291°C (from MeOH). H NMR (300
MHz, DMSO-d6, 25°C) : d = 2.60 (s, 3 H, 5'-SO 2Me), 3.74 (s, 3 H, 6'-OMe), 5.98 (s, 2 H, 1'-H), 6.43 (dd,
J = 8.5, 2.1 Hz, 1 H, 3'-H), 6.45 (d, J = 2.1 Hz, 1 H, 4'-H), 7.60 (d, J = 8.5 Hz, 1 H, 2'-H), 7.65 (dd, J =
8.5, 6.8 Hz, 1 H, 2-H), 7.66 (ddd, J = 8.5, 6.6, 1.1 Hz, 1 H, 7-H), 7.88 (ddd, J = 8.4, 6.6, 1.5 Hz, 1 H, 6-H),
7.95 (dd, J = 6.8, 1.3 Hz, 1 H, 3-H), 8.12 (dd, J = 8.5, 1.3 Hz, 1 H, 1-H*), 8.19 (dd, J = 8.5, 1.5 Hz, 1 H,
13
8-H*), 8.21 (dd, J = 8.4, 1.1 Hz, 1 H, 5-H), 9.15 (s, 1 H, 9-H) ppm. C NMR (75 MHz, DMSO-d6,
25°C) : d = 39.58 (5'-SO2Me), 55.24 (6'-OMe), 61.82 (C-1'), 102.61 (C-4'), 104.69 (C-2'a), 111.85 (C-3'),
125.78 (C-2), 126.05 (C-9a), 126.19 (C-7), 126.35 (C-8a), 127.31 (C-3), 127.91 (C-8*), 128.69 (C-1*),
129.36 (C-5), 130.91 (C-6), 132.73 (C-2'), 135.06 (C-4), 136.79 (C-9), 146.20 (C-4a), 147.87 (C-10a),
158.78 (C-3'a), 161.27 (C-4'a), 165.40 (C-2'b) ppm. Anal. Calcd for C23H20N2O5S: C, 63.29; H, 4.62; N,
6.42. Found: C, 63.41; H, 4.61; N, 6.41.
Acridin-4-ylmethyl 2-(N,N-dimethylamino)acetate (8k): A solution of alcohol (7) (500 mg, 2.39 mmol),
N,N-dimethylglycine hydrochloride (367 mg, 2.63), DMAP (321 mg, 2.63) and DCC (542 mg, 2.63) in
Me2CO (15 mL) was stirred for 96 h at rt under dry atmosphere (CaCl2). Me2CO (50 mL) was then added
and the precipitated DCU was filtered off. The solvent was removed under vacuo, the mixture was
dissolved in CH2Cl2 (20 mL), washed with NaOH (1N, 10 mL) and extracted with HCl (1N, 3 ¥ 10 mL).
The acidic aqueous layer was neutralized with 1N NaOH, extracted with CH2Cl2 (3 ¥ 20 mL),the resulting
organic layer was dried with Na2SO4 and the solvent was removed under vacuo. The resulting oil was
purified by column chromatography (CH2Cl2/EtOAc, 5:5, v/v) to give pure 8k as a brown oil (515 mg,
73%). 1H NMR (300 MHz, CDCl3, 25°C) : d = 2.39 (s, 6 H, 3'-NMe2), 3.30 (s, 2 H, 2'-CH2), 6.05 (s, 2 H,
1'-H), 7.48 (dd, J = 8.5, 7.0 Hz, 1 H, 2-H), 7.52 (ddd, J = 7.8, 6.8, 0.8 Hz, 1 H, 7-H), 7.75 (ddd, J = 8.5,
6.8, 1.3 Hz, 1 H, 6-H), 7.77 (dd, J = 7.0, 1.2 Hz, 1 H, 3-H), 7.94 (dd, J = 8.5, 1.2 Hz, 1 H, 1-H), 7.97 (dd,
J = 7.8, 1.3 Hz, 1 H, 8-H), 8.22 (dd, J = 8.5, 0.8 Hz, 1 H, 5-H), 8.73 (s, 1 H, 9-H) ppm. 13C NMR (75
MHz, CDCl3, 25°C) : d = 45.31 (3'-NMe2), 60.57 (2'-CH2), 63.28 (C-1'), 125.11 (C-2), 125.85 (C-7),
126.28 (C-9a), 126.53 (C-8a), 127.96 (C-3), 128.38 (C-8**), 128.59 (C-1**), 129.95 (C-5*), 130.14
(C-6*), 134.05 (C-4), 135.87 (C-9), 146.84 (C-4a), 148.54 (C-10a), 170.66 (C-2a') ppm. Anal. Calcd for
C18H18N2O2: C, 73.45; H, 6.16; N, 9.52. Found: C, 73.30; H, 6.17; N, 9.51.
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