Synthesis of substituted 1,4-benzoxazepin-3-one derivatives

Article abstract of DOI:10.3987/com-04-10022

A synthesis of substituted 1,4-benzoxazepin-3-one is described starting from salicylaldehyde, aniline and chloroacetyl chloride. Use of 2-bromo-3-phenylpropionyl chloride gave access to 2-benzyl-1,4-benzoxazepin-3-one; an addition/elimination sequence afforded the corresponding benzylidene derivative which structure has been confirmed by an X-Ray analysis. Biphenyl substituents were also introduced in position -4 of this scaffold.

Full text of DOI:10.3987/com-04-10022

HETEROCYCLES, Vol. 63, No. 5, 2004, pp. 1093 - 1112
Received, 23rd January, 2004, Accepted, 4th March, 2004, Published online, 12th March, 2004
SYNTHESIS OF SUBSTITUTED 1,4-BENZOXAZEPIN-3-ONE
DERIVATIVES
Yann Davion ,a Gérald Guillaumet,a Jean-Michel Léger,b Christian Jarry,b
Brigitte Lesur,c and Jean-Yves Méroura*
aInstitut de Chimie Organique et Analytique, UMR C.N.R.S. 6005, Université
d’Orléans, B.P. 6759, 45067 Orléans Cedex, France E-mail : jean-yves.merour
@univ-orleans.fr
bEA Pharmacochimie 2962, Université Victor Ségalen Bordeaux 2, 33076
Bordeaux Cedex, France
cCephalon France, 19 Avenue du Professeur Cadiot, 94701 Maisons-Alfort,
France
Abstract- A synthesis of substituted 1,4-benzoxazepin-3-one is described starting
from salicylaldehyde, aniline and chloroacetyl chloride. Use of 2-bromo-3-
phenylpropionyl chloride gave access to 2-benzyl-1,4-benzoxazepin-3-one; an
addition/elimination sequence afforded the corresponding benzylidene derivative
which structure has been confirmed by an X-Ray analysis. Biphenyl substituents
were also introduced in position -4 of this scaffold.
The design of new scaffolds for mimicking peptidic backbone is always of interest for medicinal
chemistry. Among the numerous heterocyclic structures which have been reported we can mention the
pyrrolidone ring or the benzodiazepine skeleton. In a program devoted to the search for new factor Xa
inhitors1 we prepared 1,4-benzoxazepin-3-one bearing in position -2 a benzylidene and in position -4 aryl
substituents. Similar structures but unsubstituted in position -2 (type A and C) have been briefly
described in the literature.2 Cyclic imides of type B have been also reported3 (Figure 1).
O
O
O
O
O
O
N
N
N
t-BuHNOC
N
N
O
R
C
A
B
Figure 1

We recently published the synthesis of eight-membered ring derivatives of benzoxazocinone type.4 In this
paper we report our results concerning the synthesis of the seven-membered ring derivatives
benzoxazepine.
Our retrosynthetic approach is outlined in Scheme 1.
OH
H
N
Ar2
O
O
Ar1
O
O
+
N
N
Cl
Cl
Ar1
Ar1
O
Scheme 1
Salicylaldehyde is first reacted with 4-methoxyaniline in refluxing ethanol followed directly at room
temperature by sodium borohydride reduction of the obtained imine to give 1a in 99% yield. 1a is further
reacted with chloroacetyl chloride5 to provide the corresponding amide (2) in good yield (93%); the cyclic
ether (3) is obtained in quantitative yield under basic treatment; these 2 steps can be performed “one pot”
without isolation of 2 before cyclization.
O
Cl
Cl
OH
OH
N
O
Et3N, CH2Cl2
0°C, 2 h
K2CO3, acetone
reflux, 2.5 h
O
N
quant.
93 %
HN
O
OMe
OMe
Cl
OMe
1a
2
3
Scheme 2
Unfortunately we were not able to introduce the benzylidene moiety in position –2 via an aldol type
reaction between compound (3) and piperonal using different set of reaction conditions and reagents
(LDA/THF,6 EtONa/EtOH or Ac2O7) (Scheme 3).
O
Ar
ArCHO
O
O
O
N
N
OMe
3
4
OMe
Scheme 3
We turned then on to another synthetic approach for the preparation of 4, benzyl group being introduced
before cyclization as depicted in retrosynthetic Scheme 4.

COCl
Ph
OH
N
Br
Ph
Ph
O
O
Ph
Br
+
O
O
OH
NH
N
N
O
R
R
R
R
Scheme 4
In this approach the chloroacetyl chloride reagent is replaced by 2-bromo-3-phenylpropionyl chloride (5)8
which was reacted on compounds (1a,b) affording the bromoamides (6a,b) in moderate yields (Scheme
5). 6a,b, were cyclized to compounds (7a,b) in good yields using the same basic conditions as for
conversion from 2 to 3 as reported above.
However when 1c was reacted in the same conditions, a very low yield of the expected amide was
obtained, therefore alternative access to 7c was developed; 7c was obtained by treating 7b with sodium
cyanide in acetonitrile in the presence of a catalytic amount of tetrakis(triphenylphosphine) palladium and
copper(I) iodide in 76% yield (Scheme 5).
Alternatively phenol (1c) can be first protected with a tert-butyldimethylsilyl group and successfully
converted to amide (6c) in reasonable yield (40%); further deprotection of 6c with tetrabutylammonium
fluoride (TBAF) at 0°C gave directly the expected cyclized compound (7c) in 73% yield. The structure of
7c has been confirmed by an X-Ray analysis (not reported here).
OH
OH
Br
Cl
O
K2CO3
acetone
OH
H2N
R
(5)
Et3N, CH2Cl2
Br
O
O
N
NaBH4 , EtOH
N
NH
CHO
O
R
R
1a R= OMe
1b R= I
1c R = CN
6a R= OMe 56%
6b R = I 43%
R
7a R= OMe 90%
7b R= I 73%
Pd(PPh3)4
NaCN
7c R = CN 76%
1)
NaBH4 , EtOH
OSi
H2N
(8)
NHO S
t-Bu
2
1) 1c, TBDMSCl, (iPr)2NEt
Br
TBAF, THF
0°C, 2.5 h
2) TBDMSCl, (iPr)2NEt,CH2Cl2
3) 5, Et3N, CH2Cl2
2) 5, Et3N, CH2Cl2
7c R = CN 73%
7d R =2-(t-BuNHO2S)C6H4 71%
N
O
R
6c R= CN 40%
6d R = 2-(t-BuNHO2S)C6H4 37%
Scheme 5

To further generate the exo double bond in position -2 we first investigated the radicalar bromination of
7a with NBS, but no expected bromo derivative in position -2 was observed, so we moved to an
electrophilic bromination9,10 of the amide enolate of 7a. Treatment of 7a with LDA at low temperature
followed by addition of iodine or 1,1,2,2-tetrachloro-1,2-dibromoethane at –78°C and quenching with a
saturated ammonium chloride solution at –78°C or 0°C directly gave the ethylenic derivative (4a)
(Scheme 6). The yield of 4a was higher in the bromation/elimination sequence, 65% versus 51 % yield
for the iodination/elimination sequence. No 2- iodo or 2-bromo derivative was isolated in those two
reactions conditions.
H
O
i) LDA, THF, -78°C
O
ii) (CBrCl2)2, THF, -78°C
iii) H2O, -78°C
O
O
N
N
R
R
7a R = OMe
7c R = CN
4a R = OMe
4c R = CN
4e R = C(NH2)NOH 81%
65%
55%
NH2OH
MeAlClNH2
4f R = CONH2 20%
Scheme 6
The stereochemistry of the ethylenic bond was assigned as Z, first by measuring the coupling constant
3JCH = 4.5 Hz.11-13 (For an E configuration the 3JCH value would be greater than 7 Hz, Figure 2). Moreover
an X-Ray analysis was performed on 4a confirming the structure (Figure 3).
Ph
H
O
3JCH ≤ 5 Hz
O
N
OMe
4a
Figure 2
Compound (7c) similarly afforded 4c in 55% yield. We were interested in converting the cyano group
into an amidine using a Pinner reaction; but we were unable to sucessfully perform that transformation.
We then moved to a two-step reaction by first preparing the amidoxime derivative (7e) by reacting 7c
with hydroxylamine hydrochloride in 55% yield; (Scheme 7). Hydrogenation14 of 7e over palladium on
carbon in a mixture of acetic anhydride / acetic acid under an hydrogen pressure of 3.5 atm afforded 7f in

80 % yield; the unsaturated cyano derivative (4c) similarly gave the amidoxime (4e) in 81% yield
(Scheme 6).
Figure 3. ORTEP structure of 4a
Garipati15 reported that the reaction of alkylchloroaluminium amide on benzonitrile afforded
benzamidine;16 in our case, only the benzamide (4f) was obtained in quite low yield (20 %) from 4c.
O
H2, 10% Pd/C
Ac2O, AcOH
O
O
NH2OH,HCl
EtOH
O
O
O
3.5 atm
80 %
N
N
N
55 %
NH
N
OH
H2N
N
7f
7c
7e
H2N
Scheme 7
We were also interested in introducing a 2’-SO2NHt-Bu substituted 4-biphenyl moiety on the nitrogen of
the oxazepinone since an improved activity toward inhibition of factor Xa has been reported by Wexler et
al.17 when the benzamidine moiety is replaced by a substituted biphenyl of that type.
Introduction of the biphenyl substituent was first done by reacting salicylaldehyde on the diphenylamine
(8)18,19 followed by sodium borohydride reduction of the intermediate imine to give the corresponding
amine in 63 % yield; the protection of the hydroxy group of this amine with a tert-butyldimethylsilyl
group afforded the O-protected derivative in 88 % yield; the reaction of the latter with 2-bromo-3-
phenylpropionyl chloride (5) afforded 6d in 68% yield, the global yield being 37 % from salicylaldehyde
(Scheme 5). Once again, deprotection with tetrabutylammonium fluoride (TBAF) at 0°C gave directly the

cyclized derivative (7d) in good yield (71%).
Finally a methyl acetate substituent was also introduced on the 4-nitrogen starting from the glycine
derivative (9)20 which gave access to benzoxazepinone (10) (Scheme 8). Ester (10) was hydrolyzed into
the corresponding acid, (LiOH/THF/H2O/MeOH) in 99% yield, which was further reacted with 2-(4-
pyridyl)ethylamine (11)21 in presence of 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride
(EDCI) to afford 12 in 68% yield.
OH
1) TBDMSCl, CH2Cl2 92%
O
2) 5, Et3N, CH2Cl2 70%
O
3) TBAF, THF,
77 %
O
N
NH
O
R
MeO
10 R = OMe
1) LiOH
2) EDCI, 11
CH2Cl2
9
N
12 R = NHCH2CH2
68%
Scheme 8
Conclusions
We have synthesized 1,4-benzoxazepin-3-ones variously substituted in position –2 and -4; this scaffold
can mimick peptidic backbone and therefore could be introduced as central scaffold in the synthesis of
new potentially bioactive compounds.
EXPERIMENTAL
Melting points were determined using a Kofler hot stage apparatus and were uncorrected. NMR spectra
were recorded on a Bruker instrument Avance DPX250 at 250 MHz (1H) or 62.9 MHz (13C NMR) in
CDCl3 or in DMSO-d6. Chemical shifts (δ values) were reported in parts per million and coupling
constants (J values) in Hz. IR spectra were recorded as a thin film on NaCl plates for the oils and in a KBr
pellet for the solids on a Perkin-Elmer spectrophotometer FT Paragon 1000 PC. MS spectra were
recorded on a Perkin-Elmer mass spectrometer Sciex API 300 (ionspray IS). Flash chromatography was
performed on silica gel (Merk 60, 230-400 msh). TLC was performed on pre-coated silica gel plates
(Merk 60, F254, 0.25 mm). Organic solvents used were HPLC grade or were purified by standard
procedure. All reagents were of commercial quality or were purified before use.
2-Chloro-N-(2-hydroxybenzyl)-N-(4-methoxyphenyl)acetamide (2) :To a mixture of 1a4 (694 mg, 3.03
mmol) and triethylamine (421 µL, 3.30 mmol) in dry dichloromethane (25 mL) at 0°C was added 2-
chloroacetyl chloride (565 µL, 3.64 mmol) under argon atmosphere. The resulting solution was stirred at

0°C for 2 h and evaporated in vacuo. The residue was hydrolysed in water (10 mL) and extracted with
ethyl acetate (2 x 10 mL). The combined organic layers were dried over anhydrous magnesium sulfate,
filtered and evaporated in vacuo. The crude residue was chromatographed on silica gel, eluting with
petroleum ether/ethyl acetate (70/30, v/v) affording compound (2) (858 mg, 93%) as a colorless solid; mp :
1
134°C (ethyl acetate–petroleum ether); IR (KBr, ν cm-1) : 3154 (OH), 1611 (CO); H NMR (CDCl3) : δ
3.87 (s, 5H, CH2Cl + OCH3), 4.77 (s, 2H, CH2N), 6.67 (dd, J= 1.9 Hz, J= 7.5 Hz, 1H, ArH), 6.73 (t, J= 7.5
Hz, 1H, ArH), 6.90-7.08 (m, 5H, ArH), 7.24 (dd, J= 1.9 Hz, J= 7.5 Hz, 1H, ArH), 9.04 (br s , 1H, OH); 13C
NMR (CDCl3) : δ 41.4 (CH2Cl), 51.7 (CH2N), 55. 7 (CH3O), 115.4 (2CH), 118.0 (CH), 119.6 (CH), 121.4
(C), 129.2 (2CH), 130.5 (CH), 132.0 (CH), 132.8 (C), 155.9 (C), 160.1 (C), 169.0 (CO). Anal. Calcd for
C16H16NO3Cl : C, 62.85; H, 5.27; N, 4.58. Found : C, 62.51; H, 5.15; N, 4.47; MS : m/z 306 (MH+ [35Cl]),
308 (MH+ [37Cl]).
4-(4-Methoxyphenyl)-2,3,4,5-tetrahydrobenz[f][1,4]oxazepin-3-one (3):
Procedure A (from compound (2) : To a stirred solution of 2 (713 mg, 2.33 mmol) in dry acetone (20 mL),
was added potassium carbonate (964 mg, 6.99 mmol) and the resulting suspension was heated at reflux for
2 h under oxygen free argon atmosphere. After cooling, the reaction mixture was evaporated in vacuo and
the residue diluted with water (20 mL) and extracted with ethyl acetate (2 x 10 mL). The combined organic
layers were dried over anhydrous magnesium sulfate, filtered and evaporated in vacuo. The crude residue
was chromatographed on silica gel, eluting with petroleum ether/ethyl acetate (60/40, v/v) to afford
compound (3) (519 mg, quant.) as a colorless solid.
Procedure B (from compound (1a): To a mixture of 1a4 (4.04 g, 17.6 mmol) and potassium carbonate (7.30
g, 52.9 mmol) in dry acetone (150 mL) at 0°C, was added 2-chloroacetyl chloride (1.6 mL, 19.4 mmol)
under argon atmosphere. The resulting suspension was stirred at 0°C for 1 h and allowed to warm to rt and
stirred for 18 h. Then the reaction mixture was heated to reflux for 2.5 h and after cooling, the precipitated
product was filtered off. The filtrate was evaporated in vacuo and the residue taken up in dichloromethane
(50 mL) and washed with water (50 mL). The organic layer was dried over anhydrous magnesium sulfate,
filtered and evaporated in vacuo to give 3 (4.50 g, 95%) as a colorless solid; mp : 175°C (methanol); IR
(KBr, ν cm-1) : 1665 (CO); 1H NMR (CDCl3) : δ 3.80 (s, 3H, OCH3), 4.84 (s, 4H, CH2N+CH2O), 6.90 (dd,
13
J= 2.8 Hz, J= 9.1 Hz, 2H, ArH), 7.06-7.18 (m, 4H, ArH), 7.32 (m, 2H, ArH); C NMR (CDCl3) : δ 53.3
(OCH2), 55.6 (OCH3), 72.5 (NCH2), 114.7 (2CH), 120.2 (CH), 123.8 (CH), 127.4 (2CH), 128.3 (C), 128.8
(CH), 130.4 (CH), 136.7 (C), 157.5 (C), 158.5 (C), 168.9 (CO). Anal. Calcd for C16H15NO3 : C, 71.36; H,
5.61; N, 5.20. Found : C, 71.65; H, 5.50; N, 5.12; MS : m/z=270 (MH+).
2-(Z)-Benzylidene-4-(4-methoxyphenyl)-2,3,4,5-tetrahydrobenz[f][1,4]oxazepin-3-one (4a): To
a
stirred solution of 7a (303 mg, 0.84 mmol) in dry tetrahydrofuran (5 mL) at –78°C, was added dropwise
2M LDA (632 µL, 1.26 mmol) and the resulting solution was stirred for 1 h under argon atmosphere. At –

78°C was added dropwise 1,2-dibromo-1,1,2,2-tetrachloroethane (206 mg, 1.26 mmol) in dry
tetrahydrofuran (5 mL) and the resulting mixture was further stirred at –78°C for 2.5 h. The reaction
mixture was hydrolyzed with water (15 mL), extracted with ethyl acetate (2 x 10 mL) and washed with a
solution of sodium hydrogensulfide (10 mL). The combined organic layers were dried over anhydrous
magnesium sulfate, filtered and evaporated in vacuo. The crude residue was chromatographed on silica gel,
eluting with petroleum ether/ethyl acetate (80/20, v/v) to afford compound (4a) (195 mg, 65%) as an
1
yellow oil; IR (film, ν cm-1) : 1658 (CO); H NMR (CDCl3) : δ 3.79 (s, 3H, OCH3), 4.79 (s, 2H, NCH2),
6.71 (s, 1H, =CH), 6.90 (dd, J= 2.0 Hz, J= 8.3 Hz, 2H, ArH), 7.06-7.16 (m, 4H, ArH), 7.23-7.42 (m, 5H,
ArH), 7.84 (dd, J= 2.0 Hz, J= 8.3 Hz, 2H, ArH); 13C NMR (CDCl3) : δ 52.0 (CH2N), 55.5 (OCH3), 114.7
(2CH), 117.0 (CH), 120.4 (CH), 124.3 (CH), 127.4 (2CH), 127.9 (CH), 128.1 (CH), 128.5 (2CH), 129.4
(C), 130.1 (2CH), 130.2 (CH), 134.1 (C), 136.1 (C), 148.3 (C), 154.7 (C), 158.5 (C), 163.7 (CO). Anal.
Calcd for C23H19NO3 : C, 77.29; H, 5.36; N, 3.92. Found : C, 77.60; H, 5.45; N, 4.06; MS : m/z 358 (MH+),
380 (M + Na+).
4-[{2-(Z)-Benzylidene-3-oxo-2,3,4,5-tetrahydrobenz[f][1,4]oxazepin-4-yl}]benzonitrile (4c): Similarly
obtained as for 4a starting from 7c; reaction time 1.5 h; light brown solid m = 440 mg, 55%; mp : 186°C
1
(ethyl acetate–petroleum ether); IR (KBr, ν cm-1) : 2225 (CN), 1669 (CO); H NMR (CDCl3) : δ 4.90 (s,
2H, CH2N), 6.75 (s, 1H, =CH), 7.10-7.36 (m, 4H, ArH), 7.39-7.45 (m, 5H, ArH), 7.69 (dd, J= 1.8 Hz, J=
13
8.1 Hz, 2H, ArH), 7.86 (dd, J= 1.8 Hz, J= 8.1 Hz, 2H, ArH); C NMR (CDCl3) : δ 51.4 (CH2N), 110.6
(CN), 118.4 (C), 118.5 (CH), 120.6 (CH), 124.7 (CH), 126.7 (2CH), 127.9 (CH), 128.5 (C), 128.6 (CH),
128.7 (2CH), 130.2 (2CH), 130.8 (CH), 133.3 (2CH), 133.7 (C), 146.9 (C), 147.4 (C), 154.7 (C), 163.5
(CO). Anal. Calcd for C23H16N2O2 : C, 78.39 ; H, 4.58 ; N, 7.95. Found : C, 78.45 ; H, 4.66 ; N, 8.06 ; MS :
m/z 353 (MH+), 375 (M + Na+).
4-[2-(Z)-Benzylidene-3-oxo-2,3,4,5-tetrahydrobenz[f][1,4]oxazepin-4-yl]-N’-hydroxybenzamidine
(4e): To a stirred solution of 4c (866 mg, 2.45 mmol) in ethanol–water (300 mL, 1 : 1 v/v) was
successively added hydroxylamine hydrochloride (768 mg, 11.1 mmol) and sodium carbonate (649 mg, 6.1
mmol). The resulting mixture was heated at reflux for 48 h and cooled to 0°C. The preciptated product was
filtered off to give 4e (566 mg) as a colorless solid. The filtrate was concentrated in vacuo and the crude
residue was chromatographed on silica gel, eluting with dichloromethane/ethyl acetate (50/50, v/v) to give
compound (4e) (182 mg) as a colorless solid in a total yield of 81%; mp : 223°C (methanol); IR (KBr, ν
cm-1) : 3424 (OH, NH), 1663 (CO); 1H NMR (DMSO-d6) : δ 4.98 (s, 2H, CH2N), 5.85 (s, 2H, NH2), 6.58
(s, 1H, =CH), 7.15 (dd, J= 1.1 Hz, J= 7.5 Hz, 1H, ArH), 7.25 (d, J= 8.5 Hz, 2H, ArH), 7.31-7.46 (m, 6H,
13
ArH), 7.70 (d, J= 8.5 Hz, 2H, ArH), 7.86 (d, J= 7.5 Hz, 2H, ArH), 9.67 (s, 1H, OH); C NMR (DMSO-
d6) : δ 50.3 (CH2N), 115.7 (CH), 119.4 (CH), 124.3 (CH), 125.37 (CH), 125.44 (CH), 126.1 (CH), 128.2
(CH), 128.3 (CH), 128.4 (C), 128.7 (2CH), 128.8 (CH), 129.7 (2CH), 130.3 (CH), 131.7 (C), 133.6 (C),

142.7 (C), 148.1 (C), 150.3 (C), 153.9 (CN), 162.6 (CO). Anal. Calcd for C23H19N3O3 : C, 71.68; H, 4.97;
N, 10.90. Found : C, 71.39; H, 5.13; N, 11.04; MS : m/z 386.5 (MH+).
4-[{2-(Z)-Benzylidene-3-oxo-2,3,4,5-tetrahydrobenz[f][1,4]oxazepin-4-yl}]benzamide (4f): To a stirred
solution of 4c (134 mg, 0.38 mmol) in dry toluene (1 mL) was added dropwise a freshly prepared solution
of 1.25 M methylchloroaluminium amide (320 µL, 0.38 mmol) under argon atmosphere and the resulting
solution was heated at reflux for 24 h. The cooled mixture was filtered to give 4f (30 mg, 20%) as a light
pink solid; mp: 194°C (ethyl acetate–petroleum ether); IR (KBr, ν cm-1) : 3392 (NH), 1690 (CO); 1H NMR
(DMSO-d6) : δ 4.88 (s, 2H, CH2N), 6.81 (s, 1H, =CH), 7.16-7.37 (m, 4H, ArH), 7.40-7.51 (m, 5H, ArH),
7.65 (dd, J= 1.7 Hz, J= 8.3 Hz, 2H, ArH), 7.74 (dd, J= 1.7 Hz, J= 8.3 Hz, 2H, ArH), 7.98 (br s, 2H, NH2);
13C NMR (DMSO-d6) : δ 52.4 (CH2N), 118.4 (C), 118.6 (CH), 120.4 (CH), 121.6 (CH), 123.0 (C), 125.1
(2CH), 126.3 (CH), 128.1 (2CH), 128.2 (2CH), 129.3 (CH), 129.6 (CH), 129.7 (2CH), 132.0 (C), 137.6 (C),
145.1 (C), 156.2 (C), 167.2 (CO), 168.8 (CO). Anal. Calcd for C23H18N2O3 : C, 74.58; H, 4.90; N, 7.56.
Found : C, 74.87; H, 5.03; N, 7.68; MS : m/z 371 (MH+), 393 (M + Na+).
2-Bromo-N-(2-hydroxybenzyl)-N-(4-methoxyphenyl)-3-phenylpropionamide (6a): To a stirred solution
of 1a4 (232 mg, 1.01 mmol) in dry dichloromethane (6 mL) at 0°C was added dropwise 2-bromo-3-
phenylpropionyl chloride (5)8 (625 mg, 2.52 mmol) in dry dichloromethane (10 mL) and triethylamine
(141 µL, 1.01 mmol) under oxygen free argon atmosphere. The resulting solution was allowed to warm to
rt and stirred for 24 h. The mixture was hydrolysed with water (20 mL) and the aqueous layer extracted
with dichloromethane (2 x 10 mL). The combined extracts were dried over anhydrous magnesium sulfate,
filtered and evaporated in vacuo. The crude residue was chromatographed on silica gel, eluting with
petroleum ether/ethyl acetate (80/20, v/v) to afford compound (6a) (246 mg, 56%) as an yellow oil; IR
(film, ν cm-1) : 3205 (OH), 1690 (CO); 1H NMR (CDCl3) : δ 3.10 (dd, J= 4.7 Hz, J= 13.0 Hz, 1H, CH2Ph),
3.59 (dd, J= 11.0 Hz, J= 13.0 Hz, 1H, CH2Ph), 3.85 (s, 3H, OCH3), 4.20 (dd, J= 4.7 Hz, J= 11.0 Hz, 1H,
CHBr), 4.31 (d, J= 14.3 Hz, 1H, CH2N), 5.02 (d, J= 14.3 Hz, 1H, CH2N), 6.51 (dd, J= 1.6 Hz, J= 7.6 Hz,
1H, ArH), 6.62-6.64 (m, 1H, ArH), 6.89 (dd, J= 1.6 Hz, J= 7.6 Hz, 1H, ArH), 6.94 (d, J= 6.9 Hz, 1H, ArH),
7.03-7.33 (m, 8H, ArH), 9.38 (s, 1H, OH); 13C NMR (CDCl3) : δ 41.7 (CH2Ph), 42.7 (CHBr), 51.3 (CH2N),
55.5 (OCH3), 114.9 (CH), 117.8 (2CH), 119.2 (2CH), 121.3 (C), 126.1 (CH), 127.4 (2CH), 129.5 (3CH),
130.3 (CH), 131.9 (CH), 132.6 (C), 136.6 (C), 155.9 (C), 159.7 (C), 171.1 (CO). Anal. Calcd for
C23H22NO3Br: C, 62.74; H, 5.04; N, 3.18. Found : C, 62.97; H, 4.91; N, 3.33; MS : m/z 440.5 (MH+ [79Br]),
442.5 (MH+ [81Br]), 462.5 (M[79Br] + Na+), 464.5 (M[81Br] + Na+).
2-Bromo-N-(2-hydroxybenzyl)-N-(4-iodophenyl)-3-phenylpropionamide (6b): Similarly obtained as
for 6a starting from 1b.4 Reaction time 3.5 h; yellow oil m =185 mg, 43%; IR (film, ν cm-1) : 3174 (OH),
1
1642 (CO); H NMR (CDCl3) : δ 3.06 (dd, J= 4.6 Hz, J= 12.9 Hz, 1H, CH2Ph), 3.56 (dd, J= 11.2 Hz, J=
12.9 Hz, 1H, CH2Ph), 4.06 (dd, J= 4.6 Hz, J= 11.2 Hz, 1H, CHBr), 4.26 (d, J= 14.3 Hz, 1H, CH2N), 4.98

(d, J= 14.3 Hz, 1H, CH2N), 6.43 (dd, J= 1.4 Hz, J= 7.5 Hz, 1H, ArH), 6.63 (dd, J= 1.4 Hz, J= 7.5 Hz, 1H,
ArH), 7.00-7.27 (m, 11H, ArH), 9.15 (s, 1H, OH); 13C NMR (CDCl3) : δ 41.7 (CH2Ph), 42.5 (CHBr), 51.1
(CH2N), 95.1 (C), 118.0 (CH), 119.4 (CH), 120.8 (C), 127.5 (2CH), 128.8 (3CH), 129.5 (3CH), 130.5
(CH), 131.8 (2CH), 136.5 (C), 139.7, (C), 155.9 (C), 170.6 (CO). Anal. Calcd for C22H19NO2BrI: C,
49.28 ; H, 3.57 ; N, 2.61. Found : C, 49.66; H, 3.66; N, 2.73; MS : m/z 536 (MH+ [79Br]), 538 (MH+ [81Br]),
558 (M[79Br] + Na+), 560 (M[81Br] + Na+).
2-Bromo-N-[2-(tert-butyldimethylsilyloxy)benzyl]-N-(4-cyanophenyl)-3-phenylpropionamide (6c):
4-[2-(tert-Butyldimethylsilyloxy)benzylamino]benzonitrile : To a stirred solution of 1c4 (992 mg, 4.42
mmol) in dry dichloromethane (10 mL) at 0°C, was added diisopropylethylamine (857 mg, 6.64 mmol) and
the resulting solution was stirred at 10°C for 10 min. At 0°C, was added a solution of tert-
butyldimethylsilyl chloride (866 mg, 5.75 mmol) in dry dichloromethane (5 mL) and the reaction mixture
was allowed to warm to rt and stirred for 18 h. Solvent was removed in vacuo and the crude residue was
chromatographed on silica gel, eluting with petroleum ether/ ethyl acetate (90/10, v/v) to afford 4-[2-(tert-
butyldimethylsilyloxy)benzylamino]benzonitrile (1.34 g, 96%) as a pale yellow oil; IR (film, ν cm-1) :
3377 (NH), 2213 (CN); 1H NMR (CDCl3) : δ 0.26 (s, 6H, Si(CH3)2), 0.99 (s, 9H, (CH3)3), 4.33 (d, J= 5.7
Hz, 2H, CH2N), 4.56 (br s, 1H, NH), 6.57 (dd, J= 2.2 Hz, J= 8.8 Hz, 2H, ArH), 6.85 (dd, J= 1.2 Hz, J= 7.7
Hz, 1H, ArH), 6.93 (dd, J= 1.2 Hz, J= 7.7 Hz, 1H, ArH), 7.15-7.27 (m, 2H, ArH), 7.41 (dd, J= 2.2 Hz, J=
13
8.8 Hz, 2H, ArH); C NMR (CDCl3) : δ -4.1 (Si(CH3)2), 18.2 (C(CH3)3), 25.7 (C(CH3)3), 43.0 (CH2N),
98.4 (CN), 112.3 (2CH), 118.6 (CH), 120.6 (C), 121.3 (CH), 128.1 (C), 128.6 (CH), 128.9 (CH), 133.6
(2CH), 151.4 (C), 153.6 (C). Anal. Calcd for C20H26N2OSi : C, 70.96; H, 7.74; N, 8.28. Found : C, 71.29;
H, 7.60; N, 8.37; MS : m/z 339 (MH+).
2-Bromo N-[2-(tert-butyldimethylsilyloxy)benzyl]-N-(4-cyanophenyl)-3-phenylpropionamide (6c) To a
stirred solution of 4-[2-(tert-butyldimethylsilyloxy)benzylamino]benzonitrile (1.30 g, 3.84 mmol) in dry
dichloromethane (15 mL) at 0°C was added dropwise via syringe, a solution of 2-bromo-3-phenylpropionyl
chloride (5)8 (1.42 g, 5.8 mmol) in dry dichloromethane (20 mL) and triethylamine (800 µL, 5.80 mmol)
under argon atmosphere. The resulting solution was allowed to warm to rt and stirred for 24 h. The mixture
was hydrolysed with water (20 mL) and aqueous layer extracted with dichloromethane (2 x 10 mL). The
combined extracts were dried over anhydrous magnesium sulfate, filtered and evaporated in vacuo. The
crude residue was chromatographed on silica gel, eluting with petroleum ether/ethyl acetate (80/20, v/v) to
1
give compound (6c) (850 mg, 40%) as an orange oil; IR (film, ν cm-1) : 2230 (CN), 1686 (CO); H NMR
(CDCl3, rotamer A) : δ 0.03 (s, 3H, Si(CH3)2), 0.06 (s, 3H, Si(CH3)2), 0.82 (s, 9H, (CH3)3), 3.05 (dd, J= 4.1
Hz, J= 12.4 Hz, 1H, CH2Ph), 3.51 (dd, J= 10.6 Hz, J= 12.4 Hz, 1H, CH2Ph), 4.07-4.14 (m, 1H, CHBr),
4.75 (d, J= 14.8 Hz, 1H, CH2N), 4.97 (d, J= 14.8 Hz, 1H, CH2N), 6.65 (m, 3H, ArH), 6.81 (t, J= 7.3 Hz,
1H, ArH), 6.97-7.13 (m, 4H, ArH), 7.26-7.34 (m, 3H, ArH), 7.46 (d, J= 8.2 Hz, 2H, ArH); 1H NMR

(CDCl3, rotamer B) : δ 0.04 (s, 3H, Si(CH3)2), 0.10 (s, 3H, Si(CH3)2), 0.83 (s, 9H, (CH3)3), 3.12 (dd, J= 4.1
Hz, J= 12.5 Hz, 1H, CH2Ph), 3.62 (dd, J= 10.6 Hz, J= 12.5 Hz, 1H, CH2Ph), 4.07-4.14 (m, 1H, CHBr),
4.77 (d, J= 14.5 Hz, 1H, CH2N), 4.97 (d, J= 14.5 Hz, 1H, CH2N), 6.65 (ml, 3H, ArH), 6.81 (t, J= 7.3 Hz,
1H, ArH), 6.97-7.13 (m, 4H, ArH), 7.26-7.34 (m, 3H, ArH), 7.46 (d, J= 8.2 Hz, 2H, ArH); 13C NMR
(CDCl3, rotamer A) : δ -4.5 (Si(CH3)2), 17.9 (C(CH3)3), 25.5 (C(CH3)3), 41.1 (CH2), 42.9 (CHBr), 46.9
(CH2Ph), 112.2 (CN), 117.6 (C), 118.2 (CH), 121.3 (CH), 127.3 (CH), 128.4 (CH), 128.5 (2CH), 128.6
(2CH), 129.0 (CH), 129.5 (CH), 129.6 (CH), 129.7 (CH), 133.1 (CH), 135.9 (C), 136.8 (C), 144.7 (C),
153.1 (C), 167.6 (CO); 13C NMR (CDCl3, rotamer B) : δ -4.5 (Si(CH3)2), 17.9 (C(CH3)3), 25.5 (C(CH3)3),
41.4 (CH2), 42.9 (CHBr), 46.9 (CH2Ph), 112.2 (CN), 117.6 (C), 118.2 (CH), 121.3 (CH), 127.3 (CH),
128.4 (CH), 128.5 (2CH), 128.6 (2CH), 129.0 (CH), 129.5 (CH), 129.6 (CH), 129.7 (CH), 133.1 (CH),
135.9 (C), 136.8 (C), 144.7 (C), 153.1 (C), 167.6 (CO). Anal. Calcd for C29H33N2O2BrSi : C, 63.38; H,
6.05; N, 5.10. Found : C, 63.66; H, 5.94; N, 5.23; MS : m/z 549.5 (MH+ [79Br]), 551.5 (MH+ [81Br]), 571.5
(M[79Br] + Na+), 573.5 (M[81Br] + Na+).
2-Bromo-N-[2-(tert-butyldimethylsilyloxy)benzyl]-N-2’-(tert-butylsulfamoylbiphenyl-4-yl)-3-phenyl-
propionamide (6d):
4’-(2-Hydroxybenzylamino)biphenyl-2-N-tert-butylsulfonamide: To a stirred solution of salicylaldehyde
(208 mg, 1.70 mmol) in dry ethanol (5 mL) was added 4’-amino[1,1-biphenyl]-2-tert-butylsulfonamide
818,19 (519 mg, 1.70 mmol) in dry ethanol (5 mL) under argon atmosphere and the resulting mixture was
heated at reflux for 30 min. Sodium borohydride (64.3 mg, 1.70 mmol) was added portionwise at 0°C, and
the resulting solution was allowed to warm to rt and stirred for 16 h. After cooling, the reaction mixture
was evaporated in vacuo. The residue was dissolved in ethyl acetate (20 mL) and washed with water (10
mL) and brine (10 mL). The organic layer was dried over anhydrous magnesium sulfate, filtered and
evaporated in vacuo. The crude residue was chromatographed on silica gel, eluting with petroleum
ether/ethyl acetate (80/20, v/v) to give an yellow solid (440 mg, 63%); mp : 124°C (ethyl acetate–
1
petroleum ether); IR (KBr, ν cm-1) : 3444, 3395, 3349 (OH, NH); H NMR (CDCl3) : δ 0.97 (s, 9H,
(CH3)3), 3.69 (s, 1H, NH or OH), 4.33 (br s, 1H, NH or OH), 4.43 (s, 2H, CH2N), 6.84-6.91 (m, 4H, ArH),
7.17-7.23 (m, 2H, ArH), 7.28 (dd, J= 1.6 Hz, J= 7.5 Hz, 1H, ArH), 7.33 (d, J= 8.8 Hz, 2H, ArH), 7.44 (dd,
J= 1.5 Hz, J= 7.5 Hz, 1H, ArH), 7.53 (dd, J= 1.5 Hz, J= 7.5 Hz, 1H, ArH), 7.87 (br s, 1H, NH or OH), 8.13
(dd, J= 1.5 Hz, J= 7.5 Hz, 1H, ArH); 13C NMR (CDCl3) : δ 29.8 (C(CH3)3), 47.4 (CH2N), 54.4 (C(CH3)3),
114.8 (2CH), 116.5 (CH), 120.3 (CH), 123.2 (C), 127.5 (CH), 128.1 (CH), 129.0 (CH), 129.2 (CH), 130.6
(C), 130.9 (2CH), 131.9 (CH), 132.6 (CH), 139.9 (C), 142.2 (C), 147.7 (C), 156.1 (C). Anal. Calcd for
C23H26N2O3S : C, 67.29; H, 6.38; N, 6.82. Found : C, 67.55; H, 6.54 ; N, 6.67; MS : m/z 411.5 (MH+),
433.5 (M + Na+).
4’-[2-(tert-Butyldimethylsilyloxy)benzylamino]biphenyl-2-N-tert-butylsulfonamide: To a stirred solution of

4’-(2-hydroxybenzylamino)biphenyl-2-N-tert-butylsulfonamide (55 mg, 0.13 mmol) in dry dichloro-
methane (2 mL) at 0°C, was added diisopropylethylamine (26 mg, 0.20 mmol) and the resulting solution
was stirred at 10°C for 10 min under argon atmosphere. At 0°C, was added tert-butyldimethylsilyl chloride
(26 mg, 0.17 mmol) in dry dichloromethane (0.5 mL) and the reaction mixture was allowed to warm to rt
and stirred for 20 h. Solvents were removed in vacuo and the crude residue was chromatographed on silica
gel, eluting with petroleum ether/ethyl acetate (90/10, v/v) to afford a colorless oil (62 mg, 88%); IR (film,
ν cm-1) : 3429 (NH); 1H NMR (CDCl3) : δ 0.28 (s, 6H, Si(CH3)2), 0.94 (s, 9H, (CH3)3), 1.02 (s, 9H, (CH3)3),
3.65 (s, 1H, NH), 4.27 (br s, 2H, CH2), 4.35 (br s, 1H, NH), 6.70 (dd, J= 1.5 Hz, J= 7.8 Hz, 2H, ArH), 6.84
(dd, J= 1.5 Hz, J= 7.8 Hz, 1H, ArH), 6.90 (dd, J= 1.5 Hz, J= 7.8 Hz, 1H, ArH), 7.16 (dd, J= 1.5 Hz, J= 7.8
Hz, 1H, ArH), 7.25-7.37 (m, 4H, ArH), 7.42 (dd, J= 1.5 Hz, J= 7.8 Hz, 1H, ArH), 7.51 (dd, J= 1.5 Hz, J=
13
7.8 Hz, 1H, ArH), 8.13 (dd, J= 1.5 Hz, J= 7.8 Hz, 1H, ArH); C NMR (CDCl3) : δ -3.9 (Si(CH3)2), 18.4
(C(CH3)3), 25.9 (C(CH3)3), 29.8 (C(CH3)3), 43.7 (CH2N), 54.3 (C(CH3)3), 112.6 (2CH), 118.7 (CH), 121.3
(CH), 127.2 (CH), 127.8 (C), 128.0 (CH), 128.4 (CH), 129.2 (CH), 130.9 (2CH), 131.8 (CH), 132.6 (CH),
132.7 (C), 140.2 (C), 142.3 (C), 148.4 (C), 153.8 (C). Anal. Calcd for C29H40N2O3SSi : C, 66.37; H, 7.68;
N, 5.34. Found : C, 66.03; H, 7.87; N, 5.21; MS : m/z 525.5 (MH+).
2-Bromo-N-[2-(tert-butyldimethylsilyloxy)benzyl]-N-2’-(tert-butylsulfamoylbiphenyl-4-yl)-3-phenyl-
propionamide (6d): To a stirred solution of 4’-[2-(tert-butyldimethylsilyloxy)benzylamino]biphenyl-2-N-
tert-butylsulfonamide (1.13 g, 2.14 mmol) in dry dichloromethane (20 mL) at 0°C was added dropwise 2-
bromo-3-phenylpropionyl chloride (5)8 (795 mg, 3.2 mmol) in dry dichloromethane (15 mL) and
triethylamine (445 µL, 3.20 mmol) under argon atmosphere. The resulting solution was allowed to warm to
rt and stirred for 16 h. The mixture was hydrolysed with water (40 mL) and aqueous layer extracted with
dichloromethane (2 x 20 mL). The combined extracts were dried over anhydrous magnesium sulfate,
filtered and evaporated in vacuo. The crude residue was chromatographed on silica gel, eluting with
petroleum ether/ethyl acetate (90/10, v/v) to give compound (6d) (1.07 g, 68%) as a colorless solid; mp :
1
80°C (ethyle acetate–petroleum ether); IR (KBr, ν cm-1) : 3280 (NH), 1671 (CO); H NMR (CDCl3) : δ
0.10 (s, 3H, Si(CH3)2), 0.12 (s, 3H, Si(CH3)2), 0.90 (s, 9H, (CH3)3), 0.93 (s, 9H, (CH3)3), 3.17 (dd, J= 5.3
Hz, J= 13.2 Hz, 1H, CH2Ph), 3.35 (s, 1H, NH), 3.64 (dd, J= 10.1 Hz, J= 13.2 Hz, 1H, CH2Ph), 4.31 (dd, J=
5.3 Hz, J= 10.1 Hz, 1H, CHBr), 4.85 (d, J= 15.0 Hz, 1H, CH2N), 5.03 (d, J= 15.0 Hz, 1H, CH2N), 6.65-
6.86 (m, 4H, ArH), 6.97-7.10 (m, 2H, ArH), 7.16-7.20 (m, 2H, ArH), 7.25 (dd, J= 1.6 Hz, J= 7.7 Hz, 1H,
ArH), 7.40-7.59 (m, 7H, ArH), 8.16 (dd, J= 1.6 Hz, J= 7.7 Hz, 1H, ArH); 13C NMR (CDCl3) : δ -4.2
(Si(CH3)2), 18.2 (C(CH3)3), 25.8 (C(CH3)3), 29.8 (C(CH3)3), 41.6 (CHBr), 43.6 (CH2Ph), 47.6 (CH2N),
54.4 (C(CH3)3), 118.5 (CH), 121.3 (CH), 126.5 (C), 127.4 (CH), 127.7 (2CH), 128.2 (2CH), 128.5 (CH),
128.8 (2CH), 129.5 (CH), 129.7 (2CH), 131.0 (2CH), 132.0 (CH), 132.0 (CH), 137.2 (C), 138.8 (C), 139.8
(C), 141.1 (C), 142.1 (C), 153.3 (C), 168.4 (CO). Anal. Calcd for C38H47N2O4BrSSi : C, 62.03; H, 6.44; N,

3.81. Found : C, 62.30; H, 6.59; N, 3.68; MS : m/z 735.5 (MH+ [79Br]), 737.5 (MH+ [81Br]), 757.5 (M[79Br]
+ Na+), 759.5 (M[81Br] + Na+).
2-Benzyl-4-(4-methoxyphenyl)-2,3,4,5-tetrahydrobenz[f][1,4]oxazepin-3-one (7a): To a vigourously
stirred solution of 6a (421 mg, 0.96 mmol) in dry acetone (20 mL) was added potassium carbonate (396
mg, 2.87 mmol) and the resulting solution was heated at reflux for 3 h. After cooling, the reaction mixture
was evaporated in vacuo and the residue was taken up in ethyl acetate (10 mL) and washed with water (10
mL). The organic layer was dried over anhydrous magnesium sulfate, filtered and evaporated in vacuo. The
crude residue was chromatographed on silica gel, eluting with petroleum ether/ethyl acetate (90/10, v/v)
affording compound (7a) (311 mg, 90%) as a beige solid; mp : 138°C (ethyl acetate–petroleum ether); IR
(KBr, ν cm-1): 1674 (CO); 1H NMR (CDCl3) : δ 3.39 (dd, J= 7.0 Hz, J= 14.2 Hz, 1H, CH2Ph), 3.49 (dd, J=
4.6 Hz, J= 14.2 Hz, 1H, CH2Ph), 3.80 (s, 3H, OCH3), 4.48 (d, J= 15.8 Hz, 1H, CH2N), 4.94 (d, J= 15.8 Hz,
1H, CH2N), 5.27 (dd, J= 4.6 Hz, J= 7.0 Hz, 1H, CH), 6.89-7.10 (m, 6H, ArH), 7.24-7.49 (m, 7H, ArH); 13C
NMR (CDCl3) : δ 38.6 (CH2Ph), 53.5 (CH2N), 55.6 (OCH3), 80.3 (CH), 114.6 (2CH), 120.3 (CH), 122.9
(CH), 126.5 (C), 126.8 (CH), 127.3 (2CH), 128.3 (2CH), 128.7 (CH), 129.9 (CH), 130.2 (2CH), 136.7 (C),
137.6 (C), 156.9 (C), 158.4 (C), 169.6 (CO). Anal. Calcd for C23H21NO3 : C, 76.86; H, 5.89; N, 3.90.
Found : 76.54; 5.78; 3.74; MS : m/z 360.5 (MH+).
2-Benzyl-4-(4-iodophenyl)-2,3,4,5-tetrahydrobenz[f][1,4]oxazepin-3-one (7b): Similarly obtained as for
7a starting from 6b, reaction time 7 h; yellow solid; m =112 mg, 73%; mp : 160°C (ethyl acetate–
petroleum ether); IR (KBr, ν cm-1) : 1690 (CO); 1H NMR (CDCl3) : δ 3.38 (dd, J= 6.8 Hz, J= 16.0 Hz, 1H,
CH2Ph), 3.49 (dd, J= 4.5 Hz, J= 16.0 Hz, 1H, CH2Ph), 4.53 (d, J= 15.8 Hz, 1H, NCH2), 4.94 (d, J= 15.8
Hz, 1H, NCH2), 5.25 (dd, J= 4.5 Hz, J= 6.8 Hz, 1H, CH), 6.94 (dd, J= 2.4 Hz, J= 8.8 Hz, 2H, ArH), 7.00-
7.10 (m, 3H, ArH), 7.28-7.49 (m, 6H, ArH), 7.73 (dd, J= 2.4 Hz, J= 8.8 Hz, 2H, ArH); 13C NMR (CDCl3) :
δ 38.4 (CH2Ph), 53.0 (NCH2), 80.1 (CH), 91.9 (C), 120.3 (CH), 123.0 (CH), 125.8 (C), 126.8 (CH), 128.1
(2CH), 128.3 (2CH), 128.5 (CH), 130.0 (CH), 130.1 (2CH), 137.3 (C), 138.3 (2CH), 143.2 (C), 156.7 (C),
169.2 (CO). Anal. Calcd for C22H18NO2I: C, 58.04; H, 3.98; N, 3.08. Found : C, 57.81; H, 3.85; N, 2.94;
MS : m/z 456 (MH+), 478 (M + Na+).
4-(2-Benzyl-3-oxo-2,3,4,5-tetrahydrobenz[f][1,5]oxazepin-4-yl)benzonitrile (7c):
From 7b : To a stirred solution of 7b (1.35 g, 2.97 mmol) in deoxygenated acetonitrile (100 mL) was
successively added sodium cyanide (291 mg, 5.93 mmol), freshly prepared tetrakis-
(triphenylphosphine)palladium (514 mg, 0.45 mmol) and copper(I) iodide (85 mg, 0.45 mmol) under
argon atmosphere. The resulting solution was heated at reflux for 3.5 h and the mixture was cooled to
room temperature and hydrolysed with water (50 mL). The aqueous layer was extracted with ethyl acetate
(2 x 25 mL) and washed with brine (20 mL). The combined organic layers were dried over anhydrous
magnesium sulfate, filtered and evaporated in vacuo. The crude residue was chromatographed on silica

gel, eluting with petroleum ether/ethyl acetate (70/30, v/v) to afford compound (7c) (798 mg, 76%) as
light yellow solid.
From 6c : To a stirred solution of 6c (850 mg, 1.55 mmol) in dry dichloromethane (10 mL) at 0°C, was
added dropwise 1M tetrabutylammonium fluoride (2.64 mL, 2.64 mmol) in dichloromethane under argon
atmosphere and the resulting mixture was stirred at 0°C for 3.5 h. Solvents were removed in vacuo and the
residue was taken up in dichloromethane (10 mL) and washed with water (10 mL). The organic layer was
dried over anhydrous magnesium sulfate, filtered and evaporated in vacuo. The crude residue was
chromatographed on silica gel, eluting with petroleum ether/ethyl acetate (80/20, v/v) to give compound
(7c) (402 mg, 73%) as a light yellow solid; mp : 159°C (ethyl acetate–petroleum ether); IR (KBr, ν cm-1) :
2226 (CN), 1693 (CO); 1H NMR (CDCl3) : δ 3.32 (dd, J= 6.6 Hz, J= 14.3 Hz, 1H, CH2Ph), 3.44 (dd, J1=
4.8 Hz, J2= 14.3 Hz, 1H, CH2Ph), 4.53 (d, J= 16.0 Hz, 1H, CH2N), 4.53 (d, J= 16.0 Hz, 1H, CH2N), 5.24
(dd, J= 4.8 Hz, J= 6.6 Hz, 1H, CH), 6.96-7.08 (m, 3H, ArH), 7.24-7.31 (m, 8H, ArH), 7.63 (d, J= 8.5 Hz,
13
2H, ArH); C NMR (CDCl3) : δ 38.3 (CH2Ph), 52.9 (CH2N), 79.9 (CH), 110.3 (CN), 118.4 (C), 120.3
(CH), 123.1 (CH), 125.1 (C), 126.6 (2CH), 126.9 (CH), 128.4 (2CH), 128.6 (CH), 130.1 (2CH), 130.3
(CH), 133.1 (2CH), 137.1 (C), 147.2 (C), 156.7 (C), 169.3 (CO). Anal. Calcd for C23H18N2O2 : C, 77.95; H,
+
5.12; N, 7.90. Found : C, 78.22; H, 5.23; N, 7.99; MS : m/z 355 (MH+), 372 (M + NH4 ), 377 (M + Na+).
4’-(2-Benzyl-3-oxo-2,3,4,5-tetrahydrobenz[f][1,4]oxazepin-4-yl)biphenyl-2-N-tert-butylsulfonamide
(7d): To a stirred solution of 6d (1.07 g, 1.45 mmol) in dry dichloromethane (20 mL) at 0°C, was added
slowly a 1M Bu4NF in dry dichloromethane (1.45 mL, 1.45 mmol) under argon atmosphere and the
resulting mixture was stirred at 0°C for 2.5 h. Solvents were removed in vacuo and the residue was taken
up in dichloromethane (10 mL) and washed with water (10 mL). The organic layer was dried over
anhydrous magnesium sulfate, filtered and evaporated in vacuo. The crude residue was chromatographed
on silica gel, eluting with petroleum ether/ethyl acetate (90/10, v/v) to give compound (7d) (552 mg, 71%)
1
as a colorless solid; mp : 94°C (ethyl acetate–petroleum ether); IR (KBr, ν cm-1) : 1682 (CO); H NMR
(CDCl3) : δ 1.02 (s, 9H, (CH3)3), 3.36 (dd, J= 6.8 Hz, J= 14.3 Hz, 1H, CH2Ph), 3.46 (dd, J= 4.5 Hz, J=
14.3 Hz, 1H, CH2Ph), 3.75 (s, 1H, NH), 4.58 (d, J= 16.0 Hz, 1H, CH2N), 5.00 (d, J= 16.0 Hz, 1H, CH2N),
5.25 (dd, J= 4.5 Hz, J= 6.8 Hz, 1H, CH), 6.96-7.10 (m, 3H, ArH), 7.22-7.38 (m, 7H, ArH). 7.42-7.60 (m,
6H, ArH), 8.17 (dd, J= 1.6 Hz, J= 7.8 Hz, 1H, ArH); 13C NMR (CDCl3) : δ 29.9 (C(CH3)3), 38.6 (CH2Ph),
53.3 (CH2N), 54.6 (C(CH3)3), 80.3 (CH), 120.4 (CH), 123.1 (CH), 125.8 (2CH), 126.0 (C), 126.9 (CH),
128.1 (CH), 128.4 (3CH), 128.6 (CH), 130.1 (CH), 130.2 (2CH), 130.8 (2CH), 132.0 (CH), 132.4 (CH),
137.5 (C), 138.2 (C), 139.3 (C), 142.3 (C), 143.6 (C), 156.9 (C), 169.5 (CO). Anal. Calcd for
C32H32N2O4S : C, 71.09; H, 5.97; N, 5.18. Found : 71.44; H, 6.15; N, 5.33; MS : m/z 541 (MH+), 558.5 (M
+
+ NH4 ), 563 (M + Na+).

4-(2-Benzyl-3-oxo-2,3,4,5-tetrahydrobenz[f][1,4]oxazepin-4-yl)-N’-hydroxybenzamidine (7e): To a
stirred solution of 7c (700 mg, 1.81 mmol) in ethanol–water (200 mL, 1 : 1 v/v) was successively added
hydroxylamine hydrochloride (465 mg, 6.7 mmol) and sodium carbonate (326 mg, 3.1 mmol). The
resulting mixture was heated at reflux for 24 h and evaporated in vacuo. The crude residue was
chromatographed on silica gel, eluting with dichloromethane/ethyl acetate (10/90, v/v) to afford compound
(7e) (386 mg, 55%) as a colorless solid; mp : 189°C (methanol); IR (KBr, ν cm-1) : 3353 (OH, NH), 1677
(CO); 1H NMR (DMSO-d6) : δ 2.45 (dd, J= 8.6 Hz, J= 14.5 Hz, 1H, CH2Ph), 2.57 (dd, J= 3.8 Hz, J= 14.5
Hz, 1H, CH2Ph), 3.80 (d, J= 17.0 Hz, 1H, CH2N), 5.06 (d, J= 17.0 Hz, 1H, CH2N), 4.98 (dd, J= 3.8 Hz, J=
8.6 Hz, 1H, CH), 6.18 (d, J= 7.8 Hz, 1H, ArH), 6.29 (t, J= 7.2 Hz, 1H, ArH), 6.52-6.78 (m, 9H, ArH), 7.02
13
(d, J= 8.5 Hz, 2H, ArH); C NMR (DMSO-d6) : δ 37.4 (CH2Ph), 53.4 (CH2N), 77.6 (CH), 119.4 (CH),
122.6 (2CH), 123.7 (C), 126.1 (2CH), 126.8 (2CH), 127.2 (CH), 128.9 (2CH), 130.2 (CH), 130.3 (2CH),
131.6 (C), 138.1 (C), 144.0 (C), 151.5 (C), 156.8 (CN), 169.7 (CO). Anal. Calcd for C23H21N3O3 : C,
71.30; H, 5.46; N, 10.85. Found : C, 71.68; H, 5.33; N, 10.75 MS : m/z 388.5 (MH+).
4-(2-Benzyl-3-oxo-2,3,4,5-tetrahydrobenz[f][1,4]oxazepin-4-yl)benzamidine (7f): To a stirred solution
of 7e (299 mg, 0.77 mmol) in acetic acid (9 mL) was added acetic anhydride (162 µL, 1.7 mmol), 10%
palladium on carbon (111 mg, 37% w) and the resulting suspension was stirred at rt for 2 h under hydrogen
(3.5 bars). The reaction mixture was filtered through Celite and the filtrate evaporated in vacuo to give 7f
(227 mg, 80%) as colorless solid; mp : 204°C (methanol); IR (KBr, ν cm-1) : 3030 (NH), 1654 (CO), 1610
(CN); 1H NMR (DMSO-d6) : δ 3.16 (dd, J= 8.7 Hz, J= 14.5 Hz, 1H, CH2Ph), 3.28 (dd, J= 4.0 Hz, J= 14.5
Hz, 1H, CH2Ph), 3.42 (br s, 2H, NH2), 4.62 (d, J= 17.3 Hz, 1H, CH2N), 5.82 (dd, J= 4.0 Hz, J= 8.7 Hz, 1H,
CH), 5.92 (d, J= 17.3 Hz, 1H, CH2N), 6.88 (d, J= 6.9 Hz, 1H, ArH), 6.98 (t, J= 7.5 Hz, 1H, ArH), 7.23-
7.31 (m, 3H, ArH), 7.38 (t, J= 7.5 Hz, 2H, ArH), 7.47-7.52 (m, 4H, ArH), 7.88 (d, J= 8.5 Hz, 2H, ArH);
13C NMR (DMSO-d6) : δ 36.7 (CH2Ph), 52.4 (CH2N), 76.6 (CH), 118.6 (CH), 121.6 (CH), 122.8 (C),
125.6 (2CH), 126.4 (CH), 127.2 (C), 128.1 (2CH), 128.4 (2CH), 129.4 (CH), 129.6 (CH), 129.7 (2CH),
137.6 (C), 146.5 (C), 156.2 (CN), 169.0 (CO).; Anal. Calcd for C23H21N3O2 : C, 74.37; H, 5.70; N, 11.31.
Found : C, 74.00; H, 5.59; N, 11.23; MS : m/z 372 (MH+).
Methyl (2-benzyl-3-oxo-2,3,4,5-tetrahydrobenz[f][1,4]oxazepin-4-yl)acetate (10):
Methyl [2-(tert-butyldimethylsilyloxy)benzylamino]acetate: To a stirred solution of 919 (3.36 g, 17.2 mmol)
in dry dichloromethane (20 mL) at 0°C, was added diisopropylethylamine (4.5 mL, 25.8 mmol) and the
resulting solution was stirred at 10°C for 10 min. After cooling at 0°C, tert-butyldimethylsilyl chloride
(3.37 g, 22.4 mmol) in dry dichloromethane (10 mL) was added and the reaction mixture was allowed to
warm to rt and stirred for 22 h. Solvents were removed in vacuo and the crude residue was
chromatographed on silica gel, eluting with petroleum ether/ ethyl acetate (80/20, v/v) to give methyl [2-
(tert-butyldimethylsilyloxy)benzylamino]acetate (4.91 g, 92%) as a pale yellow oil; IR (film, ν cm-1) :

1
3347 (NH), 1747 (CO); H NMR (CDCl3) : δ 0.25 (s, 6H, Si(CH3)2), 1.02 (s, 9H, (CH3)3), 2.01 (br s, 1H,
NH), 3.40 (s, 2H, CH2), 3.69 (s, 3H, OCH3), 3.80 (s, 2H, CH2N), 6.80 (dd, J= 1.1 Hz, J= 7.6 Hz, 1H, ArH),
6.92 (dd, J= 1.1 Hz, J= 7.7 Hz, 1H, ArH), 7.13 (dd, J= 1.8 Hz, J= 7.6 Hz, 1H, ArH), 7.25 (dd, J= 1.8 Hz,
13
J= 7.5 Hz, 1H, ArH); C NMR (CDCl3) : δ -4.2 (Si(CH3)2), 18.2 (C(CH3)3), 25.8 (C(CH3)3), 48.5 (CH2),
50.0 (CH2), 51.6 (OCH3), 118.5 (CH), 121.1 (CH), 128.1 (CH), 129.9 (C), 130.0 (CH), 153.8 (C), 172.6
(CO); MS : m/z 310 (MH+).
Methyl (2-bromo-3-phenylpropionyl)-[2-(tert-butyldimethylsilyloxy)benzyl]aminoacetate : To a stirred
solution of methyl [2-(tert-butyldimethylsilyloxy)benzylamino]acetate (4.91 g, 15.9 mmol) in dry
dichloromethane (30 mL) at 0°C was added dropwise 2-bromo-3-phenylpropionyl chloride (5)8 (5.89 g,
23.8 mmol) in dry dichloromethane (40 mL) and triethylamine (3.3 mL, 23.8 mmol) under argon
atmosphere. The resulting solution was allowed to warm to rt and stirred for 16 h. The mixture was
hydrolyzed with water (50 mL) and aqueous layer was extracted with dichloromethane (2 x 25 mL). The
combined extracts were dried over anhydrous magnesium sulfate, filtered and evaporated in vacuo. The
crude residue was chromatographed on silica gel, eluting with petroleum ether/ethyl acetate (80/20, v/v)
affording compound methyl (2-bromo-3-phenylpropionyl)-[2-(tert-butyldimethylsilyloxy)benzyl]amino-
acetate (5.81 g, 70%) as a yellow oil; IR (film, ν cm-1) : 1755, 1669 (CO); two rotamers A and B were
1
observed in NMR in the ratio 70/30; H NMR (CDCl3, rotamer A) : δ 0.23 (s, 6H, Si(CH3)2), 0.98 (s, 9H,
(CH3)3), 3.10 (dd, J= 5.3 Hz, J= 13.2 Hz, 1H, CH2Ph), 3.30 (dd, J= 10.1 Hz, J= 13.2 Hz, 1H, CH2Ph), 3.57
(s, 2H, CH2CO2), 3.70 (s, 3H, OCH3), 4.32 (d, J= 16.3 Hz, 1H, CH2N), 4.43-4.47 (m, 1H, CHBr), 4.81 (d,
J= 16.3 Hz, 1H, CH2N), 6.51 (dd, J= 1.1 Hz, J= 7.2 Hz, 1H, ArH), 6.70 (dd, J= 1.1 Hz, J= 7.2 Hz, 1H,
1
ArH), 6.78 (d, J= 7.9 Hz, 1H, ArH), 7.08-7.14 (m, 2H, ArH), 7.23-7.30 (m, 4H, ArH); H NMR (CDCl3,
rotamer B) : δ 0.24 (s, 6H, Si(CH3)2), 0.99 (s, 9H, (CH3)3), 3.20 (dd, J= 5.3 Hz, J= 13.2 Hz, 1H, CH2Ph),
3.30 (dd, J= 10.1 Hz, J= 13.2 Hz, 1H, CH2Ph), 3.57 (s, 2H, CH2CO2), 3.70 (s, 3H, OCH3), 4.43-4.47 (m,
1H, CHBr), 4.52 (d, J= 16.3 Hz, 1H, CH2N), 4.85 (d, J= 16.3 Hz, 1H, CH2N), 6.51 (dd, J= 1.1 Hz, J= 7.2
Hz, 1H, ArH), 6.70 (dd, J= 1.1 Hz, J= 7.2 Hz, 1H, ArH), 6.78 (d, J= 7.9 Hz, 1H, ArH), 7.08-7.14 (m, 2H,
13
ArH), 7.23-7.30 (m, 4H, ArH); C NMR (CDCl3, rotamer A) : δ -4.1 (2CH3), 18.3 (C(CH3)3), 25.8
(C(CH3)3), 41.1 (CH2Ph), 42.5 (CHBr), 48.1 (CH2N), 48.6 (CH2CO2), 52.2 (CO2CH3), 118.4 (CH), 121.6
(CH), 125.9 (C), 127.1 (2CH), 128.6 (CH), 128.6 (2CH), 129.7 (2CH), 137.3 (C), 153.1 (C), 169.1 (CO),
169.7 (CO); 13C NMR (CDCl3, rotamer B) : δ -4.1 (2CH3), 18.3 (C(CH3)3), 25.8 (C(CH3)3), 41.0 (CH2Ph),
44.1 (CHBr), 44.7 (CH2N), 48.7 (CH2CO2), 52.4 (CO2CH3), 118.6 (CH), 121.7 (CH), 126.4 (C), 126.6
(2CH), 128.5 (CH), 128.6 (2CH), 129.6 (CH), 129.7 (CH), 137.6 (C), 153.8 (C), 169.1 (CO), 169.3 (CO);
+
+
MS : m/z 520.5 (MH+ [79Br]), 522.5 (MH+ [81Br]), 537.5 (M[79Br] + NH4 ), 539.5 (M[81Br] + NH4 ), 542.5
(M[79Br] + Na+), 544.5 (M[81Br] + Na+).
Methyl (2-benzyl-3-oxo-2,3,4,5-tetrahydrobenz[f][1,4]oxazepin-4-yl)acetate (10) : To a stirred solution of

methyl (2-bromo-3-phenylpropionyl)-[2-(tert-butyldimethylsilyloxy)benzyl]aminoacetate (6.43 g, 12.3
mmol) in dry tetrahydrofuran (20 mL) at 0°C, was added dropwise 1M Bu4NF (12.3 mL, 12.3 mmol) in
dichloromethane under argon atmosphere and the resulting mixture was stirred at 0°C for 2.5 h. Solvents
were removed in vacuo and the residue was taken up in dichloromethane (10 mL) and washed with brine (5
mL). The organic layer was dried over anhydrous magnesium sulfate, filtered and evaporated in vacuo. The
crude residue was chromatographed on silica gel, eluting with petroleum ether/ethyl acetate (70/30, v/v) to
give compound (10) (3.08 g, 77%) as an yellow solid; mp : 124-125°C (ethyl acetate–petroleum ether); IR
(KBr, ν cm-1) : 1761, 1690 (CO); 1H NMR (CDCl3) : δ 3.25 (dd, J= 8.2 Hz, J= 14.4 Hz, 1H, CH2Ph), 3.37
(dd, J= 4.1 Hz, J= 14.4 Hz, 1H, CH2Ph), 3.70 (s, 3H, OCH3), 4.04 (d, J= 17.6 Hz, 1H, CH2CO), 4.18 (d, J=
16.0 Hz, 1H, CH2N), 4.50 (d, J= 17.6 Hz, 1H, CH2CO), 4.82 (d, J= 16.0 Hz, 1H, CH2N), 5.08 (dd, J= 4.1
Hz, J= 8.2 Hz, 1H, CH), 6.89 (dd, J= 1.4 Hz, J= 7.6 Hz, 1H, ArH), 6.94 (dd, J= 1.4 Hz, J= 7.6 Hz, 1H,
13
ArH), 7.02 (dd, J= 1.4 Hz, J= 7.6 Hz, 1H, ArH), 7.15-7.33 (m, 6H, ArH); C NMR (CDCl3) : δ 38.1
(CH2), 49.9 (CH2), 51.9 (CH2), 52.3 (OCH3), 79.5 (CH), 120.1 (CH), 122.6 (CH), 125.1 (C), 126.6 (CH),
128.3 (2CH), 128.8 (CH), 129.7 (CH), 129.8 (2CH), 137.7 (C), 156.7 (C), 169.6 (CO), 170.6 (CO). Anal.
Calcd for C19H19NO4 : C, 70.14; H, 5.89; N, 4.30. Found : C, 69.88; H, 5.61; N, 4.43; MS : m/z 326
(MH+), 348 (M + Na+).
2-(2-Benzyl-3-oxo-2,3,4,5-tetrahydrobenz[f][1,4]oxazepin-4-yl)-N-[2-(4-pyridyl)ethyl]acetamide (12):
2-(2-Benzyl-3-oxo-2,3,4,5-tetrahydrobenz[f][1,4]oxazepin-4-yl)acetic acid: To a stirred solution of 10
(1.26 g, 3.88 mmol) in THF–MeOH–H2O (40 mL, 3 : 1 : 1 v/v/v) at 0°C, was added lithium hydroxide
monohydrate (325 mg, 7.76 mmol) and the resulting solution was stirred at 0°C for 1 h, and further stirred
at rt for 1 h. Solvent was removed in vacuo and the residue was taken up in dichloromethane–water (20
mL, 1 : 1 v/v) followed by an addition of conc. hydrochloric acid to pH=3. The organic layers was dried
over anhydrous magnesium sulfate, filtered and evaporated in vacuo to give (2-benzyl-3-oxo-2,3,4,5-
tetrahydrobenz[f][1,4]oxazepin-4-yl)acetic acid (1.19 g, 99%) as a white foam; mp : 144°C (methanol); IR
1
(KBr, ν cm-1) : 3061 (OH), 1740 (CO); H NMR (CDCl3) : δ 3.25 (dd, J= 8.0 Hz, J= 14.4 Hz, 1H,
CH2Ph), 3.36 (dd, J= 4.1 Hz, J= 14.4 Hz, 1H, CH2Ph), 4.06 (d, J= 17.7 Hz, 1H, CH2CO), 4.24 (d, J= 15.8
Hz, 1H, CH2N), 4.52 (d, J= 17.7 Hz, 1H, CH2CO), 4.73 (d, J= 15.8 Hz, 1H, CH2N), 5.06 (dd, J= 4.1 Hz,
J= 8.0 Hz, 1H, CH), 6.89 (d, J= 7.8 Hz, 1H, ArH), 6.96 (d, J= 7.3 Hz, 1H, ArH), 7.03 (dd, J= 1.7 Hz, J=
13
7.5 Hz, 1H, ArH), 7.01-7.25 (m, 6H, ArH), 7.73 (br s, 1H, OH); C NMR (CDCl3) : δ 38.2 (CH2), 50.3
(CH2), 51.6 (CH2), 79.9 (CH), 120.2 (CH), 123.0 (CH), 125.6 (C), 126.7 (CH), 128.4 (2 CH), 129.0 (CH),
130.0 (3 CH), 137.5 (C), 156.7 (C), 171.4 (CO), 173.5 (CO). Anal. Calcd for C18H17NO4 : C, 69.44; H,
+
5.50; N, 4.50. Found : C, 69.10; H, 5.32; N, 4.68; MS : m/z 312 (MH+), 329 (M + NH4 ), 334 (M + Na+).
2-(2-Benzyl-3-oxo-2,3,4,5-tetrahydrobenz[f][1,4]oxazepin-4-yl)-N-[2-(4-pyridyl)ethyl]acetamide (12): To a
stirred solution of (2-benzyl-3-oxo-2,3,4,5-tetrahydrobenz[f][1,4]oxazepin-4-yl)acetic acid (1.39 g, 4.47
mmol) in dry CH2Cl2 (15 mL) was added DMAP (46.8 mg, 0.38 mmol), 2-(4-pyridyl)ethylamine20 (11)

(1.04 g, 8.40 mmol) under argon atmosphere. After cooling, EDCI (807 mg, 4.20 mmol) was added at 0°C
and the resulting mixture was stirred at 0°C for 4 h and further stirred at rt for 20 h. Solvents were removed
in vacuo and the residue was taken up in dichloromethane (10 mL) and washed with water (3 x 10 mL).
The organic layer was dried over anhydrous magnesium sulfate, filtered and evaporated in vacuo. The
crude residue was chromatographed on silica gel, eluting with dichloromethane/methanol (100/2, v/v)
affording compound (12) (1.08 g, 68%) as a colorless solid; mp : 108-109°C (methanol); IR (KBr, ν cm-1) :
3298 (NH), 1683 (CO); 1H NMR (CDCl3) : δ 2.63 (t, J= 7.1 Hz, 2H, CH2Py), 3.22 (dd, J= 7.3 Hz, J= 14.3
Hz, 1H, CH2Ph), 3.29 (m, 1H, CH2Ph), 3.34-3.43 (m, 2H, CH2NH), 4.00 (d, J= 15.7 Hz, 1H, CH2CO), 4.14
(d, J= 15.7 Hz, 1H, CH2CO), 4.22 (d, J= 16.0 Hz, 1H, CH2N), 4.70 (d, J= 16.0 Hz, 1H, CH2N), 5.04 (dd,
J= 4.4 Hz, J= 7.3 Hz, 1H, CH), 6.57 (t, J= 5.8 Hz, 1H, NH), 6.89-7.04 (m, 5H, ArH), 7.16-7.27 (m, 2H,
ArH), 7.28-7.36 (m, 4H, ArH), 8.41 (d, J= 4.7 Hz, 2H, ArH); 13C NMR (CDCl3) : δ 34.7 (CH2), 38.0 (CH2),
39.4 (CH2), 51.2 (CH2), 52.4 (CH2), 79.6 (CH), 120.0 (CH), 122.9 (CH), 124.1 (2CH), 125.2 (C), 126.7
(CH), 128.2 (2CH), 128.8 (CH), 129.7 (2CH), 129.9 (CH), 137.2 (C), 147.8 (C), 149.6 (2CH), 156.4 (C),
168.5 (CO), 170.7 (CO). Anal. Calcd for C25H25N3O3 : C, 72.27; H, 6.06; N, 10.11. Found : C, 72.54; H,
5.92; N, 10.01; MS : m/z 416.5 (MH+).
X-Ray Structure Analysis of 4a : C23H19NO3, Mr (g.mol-1), 357.39; temperature 296(2) K; crystal size
0.37 x 0.22 x 0.05 mm; wavelength (λ) 1.54180 Å ; crystal system monoclinic; space group P 21/n; unit
cell dimensions a = 12.427(2) Å, α = 90°, b = 8.478(1) Å, β = 94.42(1)°, c = 17.577(1) Å, γ= 90°;
crystal volume 1846.3(4) Å3 ; Z, calculated density 4, 1.286 Mg.m-3, absorption coefficient 0.686 mm-1;
F(000) 752; θ range for data collection 4.21 to 64.93° ; index ranges -14 ≤ h ≤14, 0 ≤ k ≤9, 0 ≤l ≤ 20;
measured reflections 3130 ; Max. and min. transmission 0.9665 and 0.7855; extinction coefficient
0.0050(5). R (all data) : R1 = 0.1053 ; wR2 = 0.1623 ; Goof 1.033.
Selected bond lenghts [Å] and torsional angles[°]:C(8)-C(13) 1.324(4), C(8)-C(9); 1.489(4)), O(7)-C(8)
1.385(3), O(7)-C(8)-C(13)-C(14) -7.2(5); O(7)-C(8)-C(9)-N(10) 46.0(4), C(9)-N(10)-C(11)-C(1) -
70.8(4) C(2)-O(7)-C(8)-C(9) -6.9(5) (see indexation on Figure 1). Crystallographic data have been
deposited at the Cambridge Crystallographic Data Centre as supplementary publication no CCDC 227995.
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