Synthesis of herbicidal ZJ0273 labeled with tritium and carbon-14

Article abstract of DOI:10.1002/jlcr.1498

ZJ0273, propyl 4-(2-(4,6-dimethoxypyrimidin-2-yloxy)benzylamino)benzoate, is a broad-spectrum herbicidal ingredient used for weed control in oilseed rape in China. Two mono-labeled 2J0273, propyl 4-(2-(4,6-dimethoxypyrimidin-2-yloxy) [phenyl-3,4,5,6-

Full text of DOI:10.1002/jlcr.1498

Research Article
Received 6 December 2007,
Revised 7 January 2008,
Accepted 10 January 2008
Published online 18 February 2008 in Wiley Interscience
(www.interscience.wiley.com) DOI: 10.1002/jlcr.1498
Synthesis of herbicidal ZJ0273 labeled with
tritium and carbon-14
Ã
Ã
Zheng-Min Yang,a,b Qing-Fu Ye,c and Long Lua
ZJ0273, propyl 4-(2-(4,6-dimethoxypyrimidin-2-yloxy)benzylamino)benzoate, is a broad-spectrum herbicidal ingredient
used for weed control in oilseed rape in China. Two mono-labeled ZJ0273, propyl 4-(2-(4,6-dimethoxypyrimidin-2-
yloxy)[phenyl-3,4,5,6-3H4]benzylamino)benzoate (7) and propyl 4-(2-(4,6-dimethoxy[4,6-14C2]pyrimidin-2-yloxy)benzylami-
no)benzoate (12), were synthesized separately from [2,3,4,5,6-3H5]phenol in a four-step yield of 27% and from 4,6-dichloro-
2-(methylthio)[4,6-14C2]pyrimidine in a three-step yield of 54%. In addition, two dual-labeled analogues of ZJ0273 were
prepared by homogeneously mixing tritium-labeled ZJ0273 (7) in the benzyl ring separately with two carbon-14-labeled
ZJ0273 (2, 12) in the benzoate ring and the pyrimidine ring. These labeled ZJ0273 could be used as radiotracers in the
studies on the metabolism, mode of action, environmental behavior, and fate of ZJ0273.
Keywords: propyl 4-(2-(4,6-dimethoxypyrimidin-2-yloxy)benzylamino)benzoate; tritium; carbon-14; radiolabeled synthesis; herbicide
3,4,5,6-3H4]benzylamino)benzoate (7) (C-Ring labeled with 3H)
Introduction
and propyl 4-(2-(4,6-dimethoxy[4,6-14C2]pyrimidin-2-yloxy)benzy-
lamino)benzoate (12) (B-Ring labeled with 14C), were accom-
plished from [2,3,4,5,6-3H5]phenol (3) in four steps (Scheme 1, (a)
ZJ0273 (1, Figure 1), propyl 4-(2-(4,6-dimethoxypyrimidin-2-
yloxy)benzylamino)benzoate, is a broad-spectrum herbicidal
ingredient, which was co-developed by the Shanghai Institute
of Organic Chemistry and Zhejiang Institute of Chemical
Industry, China.1 It was formulated as herbicide under the trade
name of Youli (EC) and Youli II (SC), which obtained temporary
registration for weed control in oilseed rape in 2003.2 The
herbicides can provide effective pre- and post-emergence
control of weed at the use rate ranging from 22.5 to 52.5 g
active ingredient per hectare. ZJ0273 greatly inhibits acetolac-
tate synthase (ALS) in vivo and it has little inhibitory effect on
ALS in vitro, which differs from the typically commercial ALS
inhibitors, such as sulfonylurea and pyrimidine salicylic acid
herbicides.3 However, insufficient data are available on the
herbicidal toxicology of ZJ0273.2 Radiolabeled ZJ0273 is, there-
fore, necessary to further elucidate the precise mechanism of
action and to support the on-going studies on the environ-
mental behavior and fate of ZJ0273.
In the previous study, we synthesized propyl 4-(2-(4,6-
dimethoxypyrimidin-2-yloxy)benzylamino)[phenyl-U-14C6]benzo-
ate (2, Figure 1) (A-Ring labeled with 14C) from 4-amino[U-14C6]-
benzoic acid.4 The tracing experiments with (2) indicated that A-
Ring can undergo metabolic degradation, limiting the useful-
ness of (2) for the toxicological study to some extent.
Consequently, multi-position-labeled ZJ0273 with 3H and 14C
in the other two aromatic rings were adopted to address this
MgCl2, Et3N, CH3CN, Ar; (b) HCOH, reflux; (c) propyl 4-amino-
benzoate, MeOH, 15À201C ; (d) NaBH4, MeOH, 0À51C; (e) 4,6-
dimethoxy-2-(methylsulfonyl)pyrimidine, K2CO3, CH3CN, 50À551C)
and from 4,6-dichloro-2-(methylthio)[4,6-14C2]pyrimidine (8) in
three steps (Scheme 2, (f) MeONa, MeOH; (g) Na2WO4 Á 2H2O,
30% H2O2, AcOH, 40À501C; (h) K2CO3, CH3CN, 50À551C),
respectively. The final products (7, 12) were purified by silica gel
flash chromatography and semipreparative HPLC in the overall
yields of 27 and 54%. Their data from HPLC-MS (ESI), MS (EI), and
1H NMR analysis consisted with those of the ZJ0273 standard
sample, respectively. The chemical and radiochemical purities of
the desired products (7, 12) were found to be 498% and the
specific activity of the products were found to be 4.896 and
1.024 mCi/mmol, determined by HPLC, Radio-TLC, and HPLC-LSC
methods. Two dual-labeled analogues of ZJ0273 (13, 14) were
prepared by homogeneously mixing 3H-labeled ZJ0273 (7)
separately with two 14C-labeled ZJ0273 (2, 12) in solution. These
labeled products (7, 12, 13, 14) combining with the previously
synthesized (2) labeled with 14C could be effectively used as
aShanghai Institute of Organic Chemistry, Chinese Academy of Science,
Shanghai 200032, China
issue, thus assuring that metabolites from the radiotracers bInstitute of Pesticide Science, Northwest University of Agriculture and Forestry,
contained a 3H or 14C label. In this paper, we described our
recent preparation of mono-labeled ZJ0273 and dual-labeled
Yangling 712100, Shaanxi Province, China
cInstitute of Nuclear-Agricultural Science, Zhejiang University, Hangzhou
310029, Zhejiang Province, China
3
analogues of ZJ0273 with 14C and H, respectively (Figure 2).
*Correspondence to: Long Lu, Shanghai Institute of Organic Chemistry, Chinese
Academy of Science, No. 354, Fenglin Road, Shanghai 200032, China.
E-mail: lulong@mail.sioc.ac.cn; Qing-Fu Ye, Institute of Nuclear-Agricultural
Science, Zhejiang University, No. 268, Kaixuan Road, Hangzhou, 310029,
Results and discussion
In optimized procedures,5 the synthesis of two mono-labeled
ZJ0273, propyl 4-(2-(4,6-dimethoxypyrimidin-2-yloxy)[phenyl- Zhejiang Province, China. E-mail: qfye@zju.edu.cn
J. Label Compd. Radiopharm 2008, 51 182–186
Copyright r 2008 John Wiley & Sons, Ltd.

Z.-M. Yang et al.
MeO
OMe
MeO
OMe
B
N
N
N
N
O
O
H
N
H
N
C
14C
14C
14C
14C
14C
A
COOPr-n
14C
COOPr-n
1
2
Figure 1. ZJ0273 (1) and propyl 4-(2-(4,6-dimethoxypyrimidin-2-yloxy)benzylamino)[phenyl-U-14C6]benzoate (2).
MeO
3H
OMe
MeO
3H
OMe
14C 14C
N
N
N
N
3H
3H
O
3H
3H
O
H
N
H
N
14C
14C 14C
3H
14C 14C
3H
14C
COOPr-n
COOPr-n
13
14
Figure 2. Two dual-labeled analogues of ZJ0273 (13, 14).
3H
3H
3H
3H
OH
3H
3H
OH
3H
3H
OH
a
b
c
N
3H
3H
CHO
3H
3H
3H
COOPr-n
3
4
5
MeO
3H
OMe
3H
N
N
3H
OH
d
e
H
N
3H
3H
O
H
N
3H
3H
COOPr-n
3H
COOPr-n
6
7
Scheme 1
radiotracers in the studies on the metabolism, mode of action, aromatic rings in the molecules of ZJ0273 were labeled in the
environmental behavior, and fate of ZJ0273. study. The C-Ring of ZJ0273 centrally links the A-Ring and B-Ring
In radiosynthesis, the labeling atoms must always be located in the molecules of ZJ0273. It means that any behavior of the
in the skeleton or stable positions of the labeled molecules, so molecules must be related to C-Ring. Considering the three-ring
that the labeling atoms may not be lost in the subsequent characteristics of ZJ0273 and the previous synthesis of (2),
tracing experiments. In the molecules of ZJ0273, there are three ZJ0273 was labeled separately with 14C in the pyrimidine ring (B-
aromatic six-atom rings (A-Ring, B-Ring, and C-Ring). These three Ring) and with 3H in the benzyl ring (C-Ring). With the aid of the
aromatic rings are attractive sites for radiolabeling because of mono-labeled products (2, 7, and 12), the trace of each aromatic
their chemical and labeling stabilities. Therefore, the three ring could be revealed separately by parallel experiments so as
J. Label Compd. Radiopharm 2008, 51 182–186
Copyright r 2008 John Wiley & Sons, Ltd.
www.jlcr.org

Z.-M. Yang et al.
S
S
O
S
O
f
g
N
N
N
N
N
N
14C
14C
MeO
14C
14C
14C
14C
MeO
OMe
Cl
Cl
OMe
9
10
8
MeO
OMe
14C
N
14C
N
OH
H
N
h
O
H
N
10
COOPr-n
COOPr-n
11
12
Scheme 2
to fully track the fate of ZJ0273 in plant and soil. Two dual- from American Radiolabeled Chemicals, Inc., (Missouri, USA).
labeled analogues of ZJ0273 (13, 14) were prepared by Propyl 4-(2-(4,6-dimethoxypyrimidin-2-yloxy)benzylamino)[phe-
homogeneously combining of 3H-labeled (7) separately with nyl-U-14C6]benzoate (2) (specific activity 1.110 mCi/mmol, che-
14C-labeled (2) (radioactivity ratio 2:1) and 14C-labeled (12) mical and radiochemical purities 4 98%) was prepared in our
(radioactivity ratio 2:1). Each of dual-labeled analogues of radiochemical lab.4 Anhydrous magnesium dichloride and 4,6-
ZJ0273 could demonstrate the fate of two corresponding dichloro-2-(methylthio)pyrimidine were obtained from Sigma-
aromatic rings in the molecules simultaneously, for the activity Aldrich (USA). Paraformaldehyde, 2,5-diphenyloxazole (PPO,
of H and 14C can be distinguished.
3
Scintillation Grade, 99%) and 1,4-bis(5-phenyloxazol-2-yl)ben-
The synthesis of (4) is a key step in the four-step synthetic
process (Scheme 1). Formylation of phenol is a classic reaction in
organic chemistry and numerous traditional methods are
available.6 Most of the methods were abandoned for poor
selectivity, low yield, high toxicity, or complicated workup. The
reaction of phenol with paraformaldehyde in anhydrous
magnesium dichloride-triethylamine system was preferred for
the radiosynthesis due to its high selectivity, high yield, and
simple workup.7 The yield reached 93% in the optimized
procedures in cold reactions.5 Ethanol can quench the reaction;7
hence, ethanol in the commercially available [2,3,4,5,6-3H5]phe-
nol must be removed before reaction. To guarantee the
chemical and radiochemical purities of the final labeled
compounds, preparative HPLC was needed and the loss in the
process was the main reason for the low overall yield of product
(7). In addition, ZJ0273 can undergo O–N-type smiles rearrange-
ment to a phenol derivative under acidic condition in a good
yield at room temperature;8 hence, it should be noted that all
radiolabeled products (2, 7, 12, 13, 14) must not be kept in
acidic solution.
zene (POPOP, Scintillation Grade) were obtained from Acros
Organics (Belgium). Methanol for HPLC was of chromatographic
grade from SK Chemicals (Korea) and ultrapure water (18.2 MO/
cm, 251C) was prepared on Milli-Q academic instrument
(Millipore, France). The standard of ZJ0273 and the related
intermediates (purity exceeds 99%) were provided by the
Shanghai Institute of Organic Chemistry, China. Scintillation
cocktail was prepared as following prescription: PPO (7 g) and
POPOP (0.5 g) dissolved in the mixture of xylene (650 mL) and 2-
methoxyethanol (350mL). All the other reagents were analytical
grade and commercially available, unless otherwise stated. 1H
NMR spectra were measured on a Bruker DRX 300 spectrometer
(Bruker, Switzerland) and MS were performed on Agilent 5973
instrument (Agilent Technologies, USA). GC-MS were recorded
on Polaris Q instrument (Thermo Electron, USA) equipped with
CP-Sil88 column (50 m  0.32 mm  0.25 mm, Chrompak Instru-
ment Co., USA). HPLC-MS was conducted on Agilent 1100 LC/
MSD instrument (Agilent Technologies). HPLC analysis and
preparation were carried out on a Waters 996 series system
(Waters Co., USA) consisting of automated gradient pump,
photodiode array detector with Inertsil ODS-3 column
(4.6 mm  250 mm, GL Science Co., Japan), and Hypersil semi-
preparative column (8 mm  300 mm, Dalian Elite Co., China).
TLC was run on GF254 plates and radio-TLC plates were scanned
on Fujifilm BAS-1800II laser-based fluorescence and radioisotope
imaging system (Fuji Co., Japan). Radioactivity was determined
on WinSpectral-1414 liquid scintillation spectrometer (Wallac,
Finland).
Experimental
General
Radiochemicals [2,3,4,5,6-3H5]phenol (10.0 mCi, specific activity
5.00 mCi/mmol, radioactive concentration 1.00 mCi/mL, in etha-
nol) and 4,6-dichloro-2-(methylthio)[4,6-14C2]pyrimidine (2.5 mCi,
specific activity 50.0 mCi/mmol, solid) were purchased
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Copyright r 2008 John Wiley & Sons, Ltd.
J. Label Compd. Radiopharm 2008, 51 182–186

Z.-M. Yang et al.
2-Hydroxy[phenyl-3,4,5,6-3H4]benzldehyde (4)
carbonate (670.3 mg, 4.85 mmol) at 50À551C. The stirring was
continued for 48 h.5 The resulting mixture was filtered and
concentrated under vacuum. The residue was subjected to silica
gel flash chromatography (ethyl acetate/hexane 1:8À1:7) and
semipreparative HPLC (inject volume 200 mL; methanol/water
75:25, by vol.; flow rate 3.00 mL/min; detection UV 254.0nm;
column temperature 301C; the eluted liquid between
23.677À33.453 min were collected and concentrated) to afford
(7) (230.3mg, 39%). Radiochemical purity: 98.9%; chemical purity:
98.1%; specific activity: 4.896 mCi/mmol (determined by HPLC,5
Radio-TLC, and HLPC-LSC methods4). HPLC-MS (ESI) m/z: 424.3(M
1H1), 425.3(M1H111), 446.2(M1Na1). MS(EI, 70eV) m/z (%):
245(100), 423(M1, 62). 1H NMR (CDCl3, 300 MHz): 1.00(t, 3H,
J= 7.2 Hz, CH3), 1.74À1.75(m, 2H, J = 7.2Hz, J = 6.9Hz, CH2), 3.79(s,
6H, OCH3), 4.20(t, 2H, J = 6.9Hz, OCH2), 4.38(d, 2H, J = 5.6Hz,
NCH2), 4.67(t, J =5.4 Hz, 1H, NH), 5.77(s, 1H, CH), 6.49(d,2H,
J= 8.8 Hz, ArH), 7.15À7.40(m, 4H, HAr), 7.80(d, 2H, J = 8.8Hz,
ArH). The data were consistent with those in reference.9
To silica gel (2 g, 100À200 mesh) was added the solution
of [2,3,4,5,6-3H5]phenol in ethanol (10 mL, specific activity
5.00 mCi/mmol,
radioactive
concentration
1.00 mCi/mL)
and mixed. Ethanol was removed in vacuo under argon.
[2,3,4,5,6-3H5]phenol was eluted from silica gel with dry
acetone, followed by evaporation of acetone and dryness
over P2O5 to afford the starting material [2,3,4,5,6-3H5]
phenol (3).
To a dried Schlenck tube was added (3) (188.0 mg, 2.00mmol),
anhydrous magnesium dichloride (285.6 mg, 3.00 mmol), anhy-
drous triethylamine (727.5 mg, 7.19 mmol), and anhydrous acet-
onitrile (4 mL, refluxed for 30 min with CaH2), stirring under argon
at room temperature for 10 min. Paraformaldehyde (405.0 mg,
13.49 mmol) was added to the tube. The mixture was refluxed for
4 h and allowed to cool to room temperature.5,7 To the mixture
was added 10% HCl (5 mL), followed by extraction with ethyl
ether. The combined organic layers were washed with water and
saturated brine, dried over anhydrous MgCl2, and evaporated in
vacuo to afford (4) (229.3mg, 94%). GC-MS (EI, 70eV) m/z (%):
122(M1, 100). 1H NMR (CDCl3, 300 MHz) d: 6.98À7.06(m, 2H, ArH),
7.51À7.58(m, 2H, ArH), 9.90(s, 1H, OH), 11.04(s, 1H, CHO).
4,6-Dimethoxy-2-(methylthio)[4,6-14C2]pyrimidine (9)
To an accurately graduated flask (30.00 mL) equipped with a
condenser was added sodium (1.250 g, 54.35 mmol) and
anhydrous methanol (30 mL) at 0À51C in an ice bath under
argon. The mixture was stirred until it became clear, stirred for
another 10 min, and allowed to cool to room temperature. The
volume of the solution was increased to 30.00 mL by addition of
anhydrous methanol to the reaction mixture to afford the
solution of sodium methanolate (1.811 mmol/mL).
Propyl 4-(2-hydroxy[phenyl-3,4,5,6-3H4]benzylideneamino)-
benzoate (5)
To the stirred solution of propyl 4-aminobenzoate (336.9mg,
1.88mmol) in anhydrous methanol (2.5mL) was added (4)
(229.2mg, 1.88mmol) at 15À201C and the stirring was continued
for 1 h. The yellow precipitate formed immediately after ca.
30min. The precipitate was filtered off under vacuum, washed
with methanol (1.0mL, 0À51C), and then dried over P2O5 under
vacuum to afford (5) (425.3mg, 80%). MS (EI, 70eV) m/z
The resulting solution of sodium methanolate (2.76 mL,
5.0mmol) was added dropwise to the stirred solution of 4,6-
dichloro-2-(methylthio)[4,6-14C2]pyrimidine (8) (9.8mg, 0.05mmol,
specific activity 50 mCi/mmol), 4,6-dichloro-2-(methylthio)pyrimi-
dine (477.9mg, 2.45 mmol) and anhydrous methanol (10mL) in
Schlenck tube over 10 min and refluxed for 5 h.5,10 Water (10mL)
was added into the vigorously stirred reaction mixture, followed
by extraction with ethyl acetate. The combined organic layers
were washed with brine, dried over anhydrous Na2SO4, and
concentrated to afford (9) (437.6mg, 94%). HPLC-MS (ESI) m/z:
187(M1H1), 188(M1H111). MS (EI, 70eV) m/z (%): 186(M1, 100),
1
(%): 283(M1, 100), 240(47), 224(48). H NMR (CDCl3, 300 MHz) d:
1.05(t, J = 7.2 Hz, 3H, CH3), 1.82(m, J = 7.2 Hz, J = 6.9 Hz, 2H, CH2),
4.30(d, J = 6.9 Hz, 2H, OCH2), 6.94À6.99(m, 2H, ArH), 7.30(d,
J = 6.9 Hz, 2H, ArH), 7.39À7.43(m, 2H, ArH), 8.11(d, J = 6.9 Hz, 2H,
ArH), 8.63(s, 1H, HC= N).
Propyl 4-(2-hydroxy[phenyl-3,4,5,6-3H4]benzylamino)benzo-
ate (6)
1
171(20), 140(29), 125(26). H NMR (CDCl3, 300 MHz) d: 2.53(s, 3H,
SCH3), 3.92(s, 6H, OCH3), 5.71(s, 1H, CH).
Sodium borohydride (80 mg, 2.11mmol) was added in portions to
the vigorously stirred suspension of (5) (424.0mg, 1.50mmol) in
anhydrous methanol (4 mL) at 0À51C. The mixture was stirred for
30min. To the resulting solution was added water (8mL) then
stirred for another 30min. The solution was concentrated in
vacuo to remove methanol and extracted with ethyl acetate. The
combined organic layers were washed with saturated brine, dried
over anhydrous Na2SO4, and evaporated under reduced pressure
to afford (6) (396.1 mg, 93%). HPLC-MS (ESI) m/z: 286(M1H1),
287(M1H111). MS (EI, 70eV) m/z (%): 285(M1, 46), 137(100),
179(36), 120(62), 107(55). 1H NMR (CD3SOCD3, 300 MHz) d: 0.93(t,
J = 7.2 Hz, 3H, CH3), 1.65(m, J = 7.2 Hz, J = 6.9 Hz, 2H, CH2), 4.11(t,
J = 6.9 Hz, 2H, OCH2), 4.30(s, 2H, NCH), 6.65(t, J = 8.7 Hz, 2H, ArH),
6.66À7.18(m, 4H, ArH), 7.72(t, J = 8.7 Hz, 2H, ArH), 9.76(s, 1H, OH).
4,6-Dimethoxy-2-(methylsulfonyl)[4,6-14C2]pyrimidine (10)
To a stirred solution of (9) (436.8 mg, 2.35 mmol) and sodium
tungstate dihydrate (40.0 mg, 0.12 mmol) in acetic acid (2 mL)
was added 30% hydrogen peroxide (0.50 mL, 4.90 mmol) at
401C. The solution was stirred for 10 min, allowed to warm to
501C, and stirred for 4 h.5,10 The mixture was cooled to room
temperature and evaporated acetic acid in vacuum. The residue
was suspended in ethyl acetate (8 mL), washed with water,
concentrated, and subjected to flash chromatograph (ethyl
acetate/hexane 1:4) to afford (10) (429.9 mg, 84%). HPLC-MS
(ESI) m/z: 219(M1H1), 220(M1H111). MS (EI, 70 eV) m/z (%):
218(M1, 28), 139(100). 1H NMR (CDCl3, 300 MHz) d: 3.32(s, 3H,
SCH3), 4.03(s, 6H, OCH3), 6.18(s, 1H, CH).
Propyl
4-(2-(4,6-dimethoxypyrimidin-2-yloxy)[phenyl-
3,4,5,6-3H4]benzylamino) benzoate (7)
Propyl 4-(2-(4,6-dimethoxy[4,6-14C2]pyrimidin-2-yloxy)ben-
zylamino)benzoate (12)
To the vigorously stirred solution of (6) (395.4mg, 1.39 mmol) and
4,6-dimethoxy-2-(methylsulfonyl)pyrimidine (302.4mg, 1.39 mmol)
A mixture of anhydrous potassium carbonate (812.7 mg,
in anhydrous acetonitrile (5 mL) was added anhydrous potassium 5.88 mmol), propyl 4-(2-hydroxybenzylamino)benzoate (11)
J. Label Compd. Radiopharm 2008, 51 182–186
Copyright r 2008 John Wiley & Sons, Ltd.
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Z.-M. Yang et al.
(558.6 mg, 1.96 mmol) and (10) (428.1 mg, 1.96 mmol) in (7) (100.0 mg, 4.896 mCi/mmol), 14C-labeled ZJ0273 (12)
anhydrous acetonitrile (4 mL) was vigorously stirred at (44.6 mg, 1.024 mCi/mmol), and ZJ0273 (1) (60.2 mg) as the
50À551C for 36 h.5 The resulting mixture was worked up above procedures.
according to the same procedures described in the preparation
of (7). The eluted liquid between 39.655–56.113 min in Acknowledgements
semipreparative HPLC (inject volume 200 mL; methanol/water
70:30; flow rate 3.00 mL/min; detection UV 254.0 nm; column
temperature 301C) was collected and evaporated under vacuum
to afford (12) (574.4 mg, 69%). Radiochemical purity: 99.4%;
chemical purity: 98.1%; specific activity: 1.024 mCi/mmol (deter-
mined by HPLC,5 Radio-TLC, and HLPC-LSC methods4). HPLC-MS
(ESI) m/z: 424(M1H1), 425(M1H111), 446(M1Na1). MS (EI,
The authors gratefully acknowledge the financial support from
Key Program of National Natural Science Foundation of China
(20632070) and Knowledge Innovation Program of the Chinese
Academy of Science (KGCX3-SYW-203).
1
70 eV) m/z (%): 423(M1, 24), 245(100). H NMR (CDCl3, 300 MHz)
REFERENCES
d: 0.99(t, J = 7.2 Hz, 3H, CH3), 1.74(m, J = 7.2 Hz, J = 6.9 Hz, 2H,
CH2), 3.81(s, 6H, OCH3), 4.19(t, J = 6.9 Hz, 2H, OCH2) , 4.38(d,
J = 5.4 Hz, 2H, NCH2), 4.67(t, J = 5.4 Hz, 1H, NH), 5.78(s, 1H, CH),
6.49(d, J = 8.7 Hz, 2H, ArH), 7.13À7.41(m, 4H, ArH), 7.81(d,
J = 8.7 Hz, 2H, ArH). The data were consistent with those in
reference.9
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The mixture of 14C-labeled ZJ0273 (2) (100.0 mg, 1.110 mCi/
mmol), 3H-labeled ZJ0273 (7) (48.4 mg, 4.896 mCi/mmol), and
ZJ0273 (1) (73.8 mg) was dissolved in acetone, followed by
evaporation under vacuum to afford 3H–14C-labeled ZJ0273 (13)
with the specific activities of 1.066 mCi/mmol for 3H and
0.500 mCi/mmol for 14C. Another 3H–14C-labeled ZJ0273 (14)
with the specific activities of 1.066 mCi/mmol for 3H and
0.484 mCi/mmol for 14C was prepared with 3H-labeled ZJ0273
1 1994, 13, 1823À1831.
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J. Label Compd. Radiopharm 2008, 51 182–186