Synthesis and biological evaluation of novel phosphonates derivatives of as potential antitumor agents

Article abstract of DOI:10.1080/10426507.2011.558363

A series of dialkyl [2-(4,6-dimethoxypyrimidin-2-yloxy)benzamido](aryl) methylphosphonates derivatives were designed and synthesized. All the new compounds were identified by elemental analysis, IR, ¹H NMR, ³¹P NMR, and MS. Their antitumor activity against KB and CNE1 cells was examined. Some of the compounds showed potential antitumor activity, which provided some hints for further study of structure modification. In particular, the compounds 6i and 6j displayed more potent cytotoxic activities against KB in comparison with 5-FU. Copyright Taylor & Francis Group, LLC.

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Phosphorus, Sulfur, and Silicon and the
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Synthesis and Biological Evaluation of
Novel Phosphonates Derivatives of As
Potential Antitumor Agents
Chuanfei Jin a , Yong-Ju Liang b , Hongwu He a & Liwu Fu b
a Key Laboratory of Pesticide & Chemical Biology, Ministry of
Education, Central China Normal University, Wuhan, People's
Republic of China
b State Key Laboratory of Oncology in South China, Cancer Center,
Sun Yat-sen University, Guangzhou, People's Republic of China
Version of record first published: 14 Oct 2011.
To cite this article: Chuanfei Jin , Yong-Ju Liang , Hongwu He & Liwu Fu (2011): Synthesis and
Biological Evaluation of Novel Phosphonates Derivatives of As Potential Antitumor Agents, Phosphorus,
Sulfur, and Silicon and the Related Elements, 186:10, 2096-2103
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Phosphorus, Sulfur, and Silicon, 186:2096–2103, 2011
Copyright ꢀC Taylor & Francis Group, LLC
ISSN: 1042-6507 print / 1563-5325 online
DOI: 10.1080/10426507.2011.558363
SYNTHESIS AND BIOLOGICAL EVALUATION OF NOVEL
PHOSPHONATES DERIVATIVES OF AS POTENTIAL
ANTITUMOR AGENTS
Chuanfei Jin,1 Yong-Ju Liang,2 Hongwu He,1 and Liwu Fu2
1Key Laboratory of Pesticide & Chemical Biology, Ministry of Education, Central
China Normal University, Wuhan, People’s Republic of China
2State Key Laboratory of Oncology in South China, Cancer Center, Sun Yat-sen
University, Guangzhou, People’s Republic of China
GRAPHICAL ABSTRACT
R1
O
OR2
OR2
N
P
NH4OH
HPO(OR2)2
CHO
N
N
R1
R1
R1
R1
R1
1
2
NH3OTs
NH2
p-TsOH
NH4OH
P(OR2)2
O
P(OR2)2
O
R1
R1
3
4
MeO
OMe
O
N
N
MeO
OMe
NH2
O
O
P(OR2)2
O
N
N
DCC,DMAP
H
N
P(OR2)2
R1
O
COOH
R1
4
5
6
Abstract A series of dialkyl [2-(4,6-dimethoxypyrimidin-2-yloxy)benzamido](aryl)
methylphosphonates derivatives were designed and synthesized. All the new compounds were
identified by elemental analysis, IR, 1H NMR, 31P NMR, and MS. Their antitumor activity
against KB and CNE1 cells was examined. Some of the compounds showed potential antitumor
activity, which provided some hints for further study of structure modification. In particular,
the compounds 6i and 6j displayed more potent cytotoxic activities against KB in comparison
with 5-FU.
[Supplemental materials are available for this article. Go to the publisher’s online edition of
Phosphorus, Sulfur, and Silicon and the Related Elements for the following free supplemental
resource: Table S1]
Keywords Phosphonate; pyrimidinylbenzoate; amide; antitumor activity
Received 30 September 2010; accepted 21 January 2011.
Address correspondence to Hongwu He, Key Laboratory of Pesticide & Chemical Biology, Min-
istry of Education, Central China Normal University, Wuhan, 430079, People’s Republic of China. E-mail:
he1208@yahoo.com.cn
2096

SYNTHESIS AND BIOLOGICAL EVALUATION OF NOVEL PHOSPHONATES DERIVATIVES 2097
INTRODUCTION
Organophosphorus compounds have found a wide range of applications in the areas
of industrial, agricultural, and medicinal chemistry owing to their biological and phys-
ical properties as well as their utility as synthetic intermediates.1 Recent studies on the
biological evaluation of α-substituted phosphonates have revealed many compounds, with
a wide range of biological effects, including herbicidal activity,2,3 insecticidal activity,4
antiviral activitity,5–7 antifungal activity,8 and antitumor agents.9–11 A number of synthetic
methods for the synthesis of α-aminoalkyl phosphonates also have been developed during
the past years.12–15 For these reasons, the synthesis of α-substituted phosphonates and their
functionalized derivatives is an important objective.
At the same time, a variety of the reports with regard to the synthetic studies of the
pyrimidine derivatives have been presented because they were documented to exhibit a
wide range of biological activities.16,17 Some pyrimidines have been reported as selective
inhibitors of tyrosine phosphorylation by the epidermal growth-factor receptor (EGFR),
and have become an important class of potential anticancer drugs.18,19 The objective of
this study was to design and synthesize novel α-substituted phosphonates by structural
modification of pyrimidinylbenzoates.
RESULTS AND DISCUSSION
Chemistry
Dialkyl phosphites were obtained by the reported method,20 and intermediates 4 were
prepared according to the reported methods.21 Compound 5 could be easily synthesized
starting from methyl 2-hydroxybenzoate and 4,6-dimethoxy-2-(methylsulfonyl)pyrimidine
(DMPS).22
Subsequent reaction of compound 5 with substituted α-amino alkylphosphonates 4
in presence of DCC, and DMAP in CH2Cl2, lead to the formation of desired molecules in
good yield. The synthetic pathway is outlined in Scheme 1, and the structures of 6a–j are
given in Table 1.
All of the reported compounds were purified over silica gel column and characterized
spectroscopically.
The evidence for the formation of the compounds was obtained from 1H NMR, 13
C
NMR, and 31P NMR spectra, which provide diagnostic tools for the positional elucidation
Table 1 The preparation of dialkyl [2-(4,6-dimethoxypyrimidin-2-yloxy)benzamido] (aryl) methylphosphonates
6a–j
Compound
R1
R2
Yield (%)
6a
6b
6c
6d
6e
6f
6g
6h
6i
H
Me
Cl
Me
Me
Me
Et
Et
Et
69
82
80
70
62
82
70
80
77
75
H
OMe
Me
F
H
Me
OMe
Et
n-Bu
n-Bu
n-Bu
6j

2098
C. JIN ET AL.
R1
O
OR2
OR2
N
P
NH4OH
HPO(OR2)2
CHO
N
N
R1
R1
R1
R1
R1
1
2
NH3OTs
NH2
p-TsOH
NH4OH
P(OR2)2
O
P(OR2)2
O
R1
R1
3
4
MeO
OMe
O
N
N
MeO
OMe
NH2
O
O
P(OR2)2
O
N
N
DCC,DMAP
H
N
P(OR2)2
R1
O
COOH
R1
4
5
6
6a: R1 = H, R2 = Me;
6c: R1 = Cl, R2 = Me;
6b: R1 = Me, R2 = Me;
6d: R1 = H, R2 = Et;
6e: R1 = OMe, R2 = Et; 6f: R1 = Me, R2 = Et;
6g: R1 = F, R2 = Et;
6h: R1 = H, R2 = n-Bu;
6i: R1 = Me, R2 = n-Bu; 6j: R1 = OMe, R2 = n-Bu;
Scheme 1
of the protons. Assignments of the signals are based on the chemical shifts and intensity
patterns. The 1H NMR spectrum of all the compounds showed singlet for one (NH) protons
at δ (7.98–8.01), another singlet for one (pyrimidine-H) proton at δ (5.71–5.78) and a singlet
for two (2 OCH3) proton at δ (3.77–3.87). Thus, on the basis of the above data the products
have been characterized as phosphonate derivatives.
13C NMR spectra of the compounds were taken in CDCl3 and the signal obtained
further confirmed the proposed structures. The compounds showed a signal at (172.8–172.9)
ppm due to (C=O) of phosphonate derivatives. All the compounds also showed a signal at
(20.1–23.1) ppm due to (P=O) of phosphonate derivatives.
Pharmacology
The in vitro antitumor activity of the synthesized compounds against two cancer cell
lines, including KB (oral carcinoma cell), and CNE1 (nasopharyngeal carcinoma cell) were
assayed by MTT method. 5-FU was used as the reference drug. Experimental details and
the table of activities (Table S1) are presented in the Supplemental Materials.

SYNTHESIS AND BIOLOGICAL EVALUATION OF NOVEL PHOSPHONATES DERIVATIVES 2099
CONCLUSIONS
In conclusion, we have reported syntheses and biological activities of a series of di-
alkyl [2-(4,6-dimethoxypyrimidin-2-yloxy)benzamido] (aryl) methylphosphonates deriva-
tives. The preliminary bioassay data showed that some of the synthesized compounds
were potential antitumor activities. Further investigations on structural optimization and
biological studies about these derivatives are still underway in our laboratory.
EXPERIMENTAL
Mass spectra were measured on a Finnigan Trace MS 2000 spectrometer. Infrared
spectra were recorded in potassium bromide pellets with a Nicolet Avatar 360 FTIR spec-
trophotometer. 1H NMR, 13C NMR, and 31P NMR spectra were recorded in CDCl3 solution
at 600 MHz (1H), 125 MHz (13C) and 243 MHz (31P) using tetramethysilane (1H, 13C) and
85% H3PO4 (31P) as internal standards with a Varian Mercury-Plus 600 spectrometer. Ele-
mental analysis was performed with an Elementar Vario EL III elementary analyzer. Melting
points (mp) were measured with an electrothermal mp apparatus and are uncorrected.
The General Synthetic Procedure for α-Aminoalkyl Phosphonates 4
The aldehyde (15 mmol) was added to ammonium hydroxide (30%, 15 mL) and the
solution was stirred for 5 h at reflux. During this time, a white precipitate formed. The
precipitate was removed by filtration and dried. Dimethyl phosphite (6 mmol) was added to
this solid and the resulting solution was stirred for about 2–5 h at 70 ◦C. p-Toluenesulfonic
acid (6 mmol) in 50 mL. ◦Tetrahydrofuran (THF) was added to the reaction mixture, which
was stirred for 2 h at 0 C. The precipitate was removed by filtration and washed with
THF (20 mL). The precipitate was added to 15 mL aqueous ammonium hydroxide (10%)
and stirred for 30 min at room temperature. Extraction with ether (100 mL), evaporation
of the solvent, and chromatography on silica gel with EtOAc/n-hexane (4:1) gave the pure
products as oils in 40–71% yields.
The General Synthetic Procedure for
2-(4,6-Dimethoxypyrimidin-2-Yloxy)Benzoic Acid 5
To 0.32 g (2.1 mmol) methyl 2-hydroxybenzoate and anhydrous K2CO3 0.59 g (4.2
mmol) in acetone (10 mL) was stirred at room temperature for 1 h. DMSP 0.49 g (2.25
mmol) was added. The reaction was continued for 18 h. Extraction with EtOAc (50 mL),
evaporation of the solvent, and chromatography on silica gel with EtOAc/n-hexane (4:1)
gave the pure products as white solid. After the solid was dissolved in acetone (20 mL),
2 mol/L NaOH was added, then stirred for another 2 h at room temperature, then 2 mol/L
HCl was added, and the compound 5 was formed.
The General Synthetic Procedure for Dialkyl
[2-(4,6-Dimethoxypyrimidin-2-Yloxy)Benzamido](Aryl)
Methylphosphonates 6a–j
A solution of compound 5 (1 mmol) in CH2Cl2 (10 mL) was stirred, followed by
the addition of intermediate 4 (1 mmol), then the reaction system was cooled down to

2100
C. JIN ET AL.
0 ◦C, and then 1,3-dicyclohexylcarbodiimide (DCC) (1 mmol) and DMAP (0.1 mmol) in
CH2Cl2 (10 mL) was added. The mixture was reacted for about 10–24 h at 25 ◦C, then 1,3-
dicyclohexylurea (DCU) was filtered off. The CH2Cl2 solvent was evaporated to the crude
product, which was purified by chromatography on silica using a mixture of petroleum
ether and ethyl acetate (4:1) as an eluant to give the target compounds in yields of 62–82%.
O, O-Dimethyl [2-(4,6-Dimethoxypyrimidin-2-Yloxy)Phenoxyamino]
(Phenyl)Methylphosphonate (6a)
White solid, mp 146.1∼147.8 ◦C; 1H NMR (CDCl3, TMS, 600 MHz): 3.54 (d, 3H,
J = 10.8 Hz, OCH3), 3.65 (d, 3H, J = 10.8 Hz, OCH3), 3.78 (s, 6H, OCH3), 5.72 (q, 1H, J =
9.6 Hz, CH), 5.77 (s, 1H, CH), 7.20∼7.52 (m, 8H, Ph-H), 7.85 (d, 1H, J = 6.0 Hz, Ph-H),
8.01 (d, 1H, J = 6.6 Hz, NH); 13C NMR (CDCl3, TMS, 125 MHz): 49.9 (Jc,p = 126.5 Hz),
53.5 (Jc,p = 21.0 Hz), 54.3, 85.5, 123.2, 126.0, 127.3, 127.8, 127.9, 128.1, 128.6, 131.1,
132.4, 134.5, 150.1, 163.4, 164.4, 172.9; 31P NMR (CDCl3): 22.7; IR (KBr,υ/cm−1): 3261
(N-H), 1669 (C=O), 1224 (P=O); MS (EI): m/z 473 (9), 363 (34), 298 (29), 258 (100),
103 (30), 68 (54); anal. calcd. For C, 55.81; H, 5.11; N, 8.88. Found: C, 55.47; H, 5.47; N,
8.72%.
O, O-Dimethyl [2-(4,6-Dimethoxypyrimidin-2-Yloxy)Phenoxyamino]
(p-Tolyl)Methylphosphonate (6b)
White solid, mp 137.7∼139.2 ◦C; 1H NMR (CDCl3, TMS, 600 MHz): 2.30 (s, 3H,
CH3), 3.55 (d, 3H, J = 10.8 Hz, OCH3), 3.65 (d, 3H, J = 10.8 Hz, OCH3), 3.79 (s, 6H,
OCH3), 5.69 (q, 1H, J = 9.6 Hz, CH), 5.76 (s, 1H, CH), 7.06∼7.51 (m, 7H, Ph-H), 7.80
(d, 1H, J = 7.2 Hz, Ph-H), 8.00 (d, 1H, J = 7.8 Hz, NH); 31P NMR (CDCl3): 23.1; IR
(KBr,υ/cm−1): 3248 (N-H), 1662 (C=O), 1217 (P=O); MS (EI): m/z 487 (9), 259 (100),
231 (21), 139 (25); anal. calcd. For C, 56.67; H, 5.38; N, 8.62. Found: C, 56.98; H, 5.74;
N, 8.36%.
O, O-Dimethyl [2-(4,6-Dimethoxypyrimidin-2-Yloxy)Phenoxyamino]
(4-Chlorophenyl)Methylphosphonate (6c)
White solid, m.p. 122.1∼123.9 ◦C; 1H NMR (CDCl3, TMS, 600 MHz): 3.58 (d, 3H,
J = 10.8 Hz, OCH3), 3.66 (d, 3H, J = 10.8 Hz, OCH3), 3.79 (s, 6H, OCH3), 5.68 (q, 1H,
J = 9.0 Hz, CH), 5.78 (s, 1H, CH), 7.20∼7.53 (m, 7H, Ph-H), 7.79 (d, 1H, J = 6.6 Hz,
Ph-H), 8.01 (d, 1H, J = 7.8 Hz, NH); 31P NMR (CDCl3): 22.7; IR (KBr,υ/cm−1): 3259
(N-H), 1669 (C=O), 1221 (P=O); MS (EI): m/z 507 (1), 139 (20), 108 (100), 79 (13); anal.
calcd. For C, 52.03; H, 4.56; N, 8.27. Found: C, 52.33; H, 4.88; N, 8.11%.
O, O-Diethyl [2-(4,6-Dimethoxypyrimidin-2-Yloxy)Phenoxyamino]
(Phenyl)Methylphosphonate (6d)
White solid, mp 151.9∼152.7 ◦C; 1H NMR (CDCl3, TMS, 600 MHz): 1.11 (t, 3H,
J = 6.6 Hz, CH3), 1.23 (t, 3H, J = 6.6 Hz, CH3), 3.78 (s, 6H, OCH3), 3.94∼4.05 (m, 4H,
OCH2), 5.69 (q, 1H, J = 9.6 Hz, CH), 5.75 (s, 1H, CH), 7.19∼7.51 (m, 8H, Ph-H), 7.87 (m,
1H, Ph-H), 8.01 (d, 1H, J = 6.0 Hz, NH); 31P NMR (CDCl3): 20.2; IR (KBr,υ/cm−1): 3239

SYNTHESIS AND BIOLOGICAL EVALUATION OF NOVEL PHOSPHONATES DERIVATIVES 2101
(N-H), 1671 (C=O), 1238 (P=O); MS (EI): m/z 501 (10), 364 (16), 258 (100), 103 (15), 77
(7); anal. calcd. For C, 57.48; H, 5.63; N, 8.38. Found: C, 57.64; H, 5.33; N, 8.30%.
O, O-Diethyl [2-(4,6-Dimethoxypyrimidin-2-Yloxy)Phenoxyamino]
(4-Methoxyphenyl)Methylphosphonate (6e)
White solid, mp 124.9∼126.7 ◦C; 1H NMR (CDCl3, TMS, 600 MHz): 1.12 (t, 3H,
J = 7.2 Hz, CH3), 1.25 (t, 3H, J = 7.2 Hz, CH3), 3.78 (s, 9H, OCH3), 3.94∼4.06 (m,
4H, OCH2), 5.62 (q, 1H, J = 11.4 Hz, CH), 5.73 (s, 1H, CH), 6.76∼7.75 (m, 8H, Ph-H),
7.99 (d, 1H, J = 6.0 Hz, NH); 13C NMR (CDCl3, TMS, 125 MHz): 16.2 (Jc,p = 19.1 Hz),
49.6 (Jc,p = 128.3 Hz), 54.2, 55.1, 62.9 (Jc,p = 21.0 Hz), 85.3, 113.8, 123.0, 125.8, 126.8,
127.6, 129.2, 130.8, 132.2, 150.0, 152.2, 163.3, 164.4, 172.7; 31P NMR (CDCl3): 20.4; IR
(KBr,υ/cm−1): 3238 (N-H), 1666 (C=O), 1250 (P=O); MS (EI): m/z 531 (14), 259 (100),
133 (16), 91 (8); anal. calcd. For C, 56.49; H, 5.69; N, 7.91. Found: C, 56.78; H, 5.22; N,
7.57%.
O, O-Diethyl [2-(4,6-Dimethoxypyrimidin-2-Yloxy)Phenoxyamino]
(p-Tolyl)Methylphosphonate (6f)
White solid, mp 125.3∼126.7 ◦C; 1H NMR (CDCl3, TMS, 600 MHz): 1.12 (t, 3H,
J = 6.6 Hz, CH3), 1.23 (t, 3H, J = 6.6 Hz, CH3), 2.30 (s, 3H, CH3), 3.80 (s, 6H, OCH3),
3.81∼4.05 (m, 4H, OCH2), 5.65 (q, 1H, J = 9.6 Hz, CH), 5.74 (s, 1H, CH), 7.03∼7.50
(m, 7H, Ph-H), 7.77 (d, 1H, J = 7.2 Hz, Ph-H), 8.00 (d, 1H, J = 7.8 Hz, NH); 31P NMR
(CDCl3): 21.0; IR (KBr,υ/cm−1): 3249 (N-H), 1662 (C=O), 1221 (P=O); MS (EI): m/z 515
(8), 259 (70), 258 (100), 119 (17); anal. calcd. For C, 58.25; H, 5.87; N, 8.15. Found: C,
58.58; H, 5.71; N, 7.90%.
O, O-Diethyl [2-(4,6-Dimethoxypyrimidin-2-Yloxy)Phenoxyamino]
(4-Fluorophenyl)Methylphosphonate (6g)
White solid, mp 128.8∼130.3 ◦C; 1H NMR (CDCl3, TMS, 600 MHz): 1.13 (t, 3H,
J = 7.2 Hz, CH3), 1.23 (t, 3H, J = 7.2 Hz, CH3), 3.78 (s, 6H, OCH3), 3.85∼4.05 (m, 4H,
OCH2), 5.65 (q, 1H, J = 9.0 Hz, CH), 5.76 (s, 1H, CH), 6.92∼7.52 (m, 7H, Ph-H), 7.79
(d, 1H, J = 6.0 Hz, Ph-H), 8.00 (d, 1H, J = 7.2 Hz, NH); 31P NMR (CDCl3): 21.1; IR
(KBr,υ/cm−1): 3245 (N-H), 1673 (C=O), 1235 (P=O); MS (EI): m/z 519 (6), 381 (14), 258
(100), 230 (5); anal. calcd. For C, 55.49; H, 5.24; N, 8.09. Found: C, 55.68; H, 5.50; N,
8.03%.
O, O-Di-n-Butyl [2-(4,6-Dimethoxypyrimidin-2-Yloxy)Phenoxyamino]
(Phenyl)Methylphosphonate (6h)
White solid, mp 72.3∼74.1 ◦C; 1H NMR (CDCl3, TMS, 600 MHz): 0.79∼0.89 (m,
6H, CH3), 1.18∼1.56 (m, 8H, CH2), 3.87 (s, 6H, OCH3), 3.71∼3.98 (m, 4H, OCH2), 5.68
(q, 1H, J = 9.0 Hz, CH), 5.73 (s, 1H, CH), 7.19∼7.49 (m, 8H, Ph-H), 7.83 (d, 1H, J =
5.4 Hz, Ph-H), 8.01 (d, 1H, J = 6.6 Hz, NH); 13C NMR (CDCl3, TMS, 125 MHz): 13.5,
18.5 (Jc,p=9.5 Hz), 32.4 (Jc,p = 23.0 Hz), 50.2 (Jc,p=126.5 Hz), 54.3, 66.7 (Jc,p = 19.3 Hz),
85.5, 123.1, 125.9, 127.4, 127.9, 128.0, 128.4, 131.1, 132.2, 135.0, 150.1, 163.3, 164.4,
172.8; 31P NMR (CDCl3): 20.1; IR (KBr, υ/cm−1): 3238 (N-H), 1664 (C=O), 1243 (P=O);

2102
C. JIN ET AL.
MS (EI): m/z 557 (7), 259 (100), 139 (11), 82 (12); anal. calcd. For C, 60.31; H, 6.51; N
7.54. Found: C, 60.52; H, 6.23; N, 7.36%.
O, O-Di-n-Butyl [2-(4,6-Dimethoxypyrimidin-2-Yloxy)Phenoxyamino]
(p-Tolyl)Methylphosphonate (6i)
White solid, mp 90.3∼91.5 ◦C; 1H NMR (CDCl3, TMS, 600 MHz): 0.79∼0.88 (m,
6H, CH3), 1.18∼1.57 (m, 8H, CH2), 2.30 (s, 3H, CH3), 3.77 (s, 6H, OCH3), 3.71∼3.98 (m,
4H, OCH2), 5.66 (q, 1H, J = 11.2 Hz, CH), 5.72 (s, 1H, CH), 7.02∼7.49 (m, 7H, Ph-H),
7.76 (d, 1H, J = 6.4 Hz, Ph-H), 7.99 (d, 1H, J = 7.6 Hz, NH); 13C NMR (CDCl3, TMS,
125 MHz): 13.5, 18.5 (Jc,p = 9.6 Hz), 21.1, 32.4 (Jc,p = 24.9 Hz), 50.0 (Jc,p = 128.5 Hz),
54.2, 66.6 (Jc,p = 19.1 Hz), 85.5, 123.1, 125.9, 127.5, 127.9, 129.2, 131.0, 131.9, 132.2,
137.6, 150.0, 163.3, 164.3, 172.8; 31P NMR (CDCl3): 21.0; IR (KBr,υ/cm−1): 3271 (N-H),
1669 (C=O), 1225 (P=O); MS (EI): m/z 571 (10), 259 (100), 139 (11), 82 (11); anal. calcd.
For C, 60.94; H, 6.70; N, 7.35. Found: C, 61.09; H, 6.50; N, 7.15%.
O, O-Di-n-Butyl [2-(4,6-Dimethoxypyrimidin-2-Yloxy)Phenoxyamino]
(4-Methoxyphenyl)Methylphosphonate (6j)
White solid, mp 86.5∼87.3 ◦C; 1H NMR (CDCl3, TMS, 600 MHz): 0.79∼0.89 (m,
6H, CH3), 1.18∼1.58 (m, 8H, CH2), 3.77 (s, 9H, OCH3), 3.71∼3.99 (m, 4H, OCH2), 5.63
(q, 1H, J = 10.0 Hz, CH), 5.71 (s, 1H, CH), 6.76 (d, 2H, J = 8.4 Hz, Ph-H), 7.17∼7.51
(m, 5H, Ph-H), 7.70 (d, 1H, J = 6.4 Hz, Ph-H), 7.98 (d, 1H, J = 6.4 Hz, NH); 31P NMR
(CDCl3): 20.4; IR (KBr, υ/cm−1): 3239 (N-H), 1664 (C=O), 1244 (P=O); MS (EI): m/z
587 (51), 260 (78), 133 (100), 121 (40); anal. calcd. For C, 59.28; H, 6.52; N, 7.15. Found:
C, 59.76; H, 6.31; N, 6.83%.
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