A convenient synthesis of 1,3-disubstituted 4-thioxo-3,4-dihydropyrido[2,3- d]pyrimidin-2(1H)-ones and 4-thioxo-3,4-dihydropyrido[4,3-d]pyrimidin-2(1H)-ones

Article abstract of DOI:10.3987/COM-11-12227

The reaction of 2-chloro-3-lithiopyridine with alkyl isothiocyanates gave the corresponding N-alkyl-2-chloropyridine-3-thiocarboxamides, which in turn were allowed to react with aryl isocyanates in the presence of sodium hydride as a base to give 3-alkyl-

Full text of DOI:10.3987/COM-11-12227

HETEROCYCLES, Vol. 83, No. 7, 2011
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HETEROCYCLES, Vol. 83, No. 7, 2011, pp. 1641 - 1647. © The Japan Institute of Heterocyclic Chemistry
Received, 5th April, 2011, Accepted, 10th May, 2011, Published online, 18th May, 2011
DOI: 10.3987/COM-11-12227
A
CONVENIENT
SYNTHESIS
OF
1,3-DISUBSTITUTED
4-THIOXO-3,4-DIHYDROPYRIDO[2,3-d]PYRIMIDIN-2(1H)-ONES AND
4-THIOXO-3,4-DIHYDROPYRIDO[4,3-d]PYRIMIDIN-2(1H)-ONES
Kazuhiro Kobayashi,* Toshihide Komatsu, Yuki Yokoi, and Hisatoshi
Konishi
Division of Applied Chemistry, Department of Chemistry and Biotechnology,
Graduate School of Engineering, Tottori University, 4-101 Koyama-minami,
Tottori 680-8552, Japan; E-mail: kkoba@chem.tottori-u.ac.jp
Abstract – The reaction of 2-chloro-3-lithiopyridine with alkyl isothiocyanates
gave the corresponding N-alkyl-2-chloropyridine-3-thiocarboxamides, which in
turn were allowed to react with aryl isocyanates in the presence of sodium hydride
as a base to give 3-alkyl-1-aryl-4-thioxo-3,4-dihydropyrido[2,3-d]pyrimidin-
2(1H)-ones. A similar sequence starting from 4-chloro-3-lithiopyridine and ethyl
isothiocyanate gave 1-aryl-3-ethyl-4-thioxo-3,4-dihydropyrido[4,3-d]pyrimidin-
2(1H)-ones, via 4-chloro-N-ethylpyridine-3-thiocarboxamide.
A survey of the literature revealed that there have been few efficient methods for the preparation of
4-thioxo-3,4-dihydropyrido[2,3-d]pyrimidin-2(1H)-ones, so far. For example, some of these derivatives
have been prepared using the reaction of benzylidenemalononitriles with 6-amino-4-thioxo-
1,2,3,4-tetrahydropyrimidin-2-one.1 However, this method requires long reaction times and suffers from
less availability of 6-amino-4-thioxo-1,2,3,4-tetrahydropyrimidin-2-one. On the other hand, we recently
reported a synthesis of 1,3-disubstituted 4-thioxo-3,4-dihydroquinazolin-2(1H)-ones by the reaction of
N-alkyl-2-fluorobenzothioamides with isocyanates in the presence of sodium hydride.2 Therefore, we
became interested in developing a new and facile method for their preparation, and expected that it should
be achieved via the reaction of secondary 2-chloropyridine-3-thiocarboxamides with isocyanates in the
presence of an appropriate base, such as sodium hydride. In this paper we wish to report the results of our
investigation, which provide an efficient method for preparing 3-alkyl-1-aryl-4-thioxo-3,4-
dihydropyrido[2,3-d]pyrimidin-2(1H)-ones.
The
synthesis
of
1-aryl-3-ethyl-4-thioxo-3,4-
dihydropyrido[4,3-d]pyrimidin-2(1H)-ones from secondary 4-chloropyridine-3- thiocarboxamides is also
described. These thioxopyridopyrimidinone derivatives are of potential interest since some compounds
having the related 4-thioxo-3,4-dihydrobenzoquinazolin-2(1H)-one skeleton have been reported to exhibit

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HETEROCYCLES, Vol. 83, No. 7, 2011
biological properties.3
First, we searched for a method for the preparation of secondary 2-chloropyridine- 3-thiocarboxamides
(2), which could serve as precursors for the desired 4-thioxo-3,4-dihydropyrido[2,3-
d]pyrimidin-2(1H)-ones (3), and expected that the reaction of 2-chloro-3-lithiopyridine, generated from
2-chloropyridine (1) and LDA under conditions reported by Gribble and Saulnier,4 with isothiocyanates
should give the desired thiocarboxamides (2) as shown in Scheme 1. As expected, the reaction of
2-chloro-3-lithiopyridine with alkyl isothiocyanate, such as ethyl, n-butyl, and cyclohexyl isothiocyanates
gave the corresponding thiocarboxamides (2) in moderate yields. However, in the cases of using benzyl
and allyl isothiocyanate the corresponding thiocarboxamides could not be obtained at all, probably due to
deprotonation of the benzylic and allylic hydrogen.
S
S
1. LDA, –78 ˚C, THF
2. RNCS, –78 ˚C
1. NaH, DMF, 0 ˚C
NR
NHR
2. ArNCO, rt
N
Cl
N
N
Ar
O
N
Cl
1
2a R = Et 47%
2b R = n-Bu 47%
2c R = c-Hex 44%
3a R = Et, Ar = Ph 58%
3b R = Et, Ar = m-Tol 61%
3c R = Et, Ar = 3-ClC6H4 59%
3d R = Et, Ar = 4-MeOC6H4 45%
3e R = Et, Ar = 1-naphthyl 57%
3f R = n-Bu, Ar = Ph 36%
3g R = n-Bu, Ar = 3-ClC6H4 41%
3h R = c-Hex, Ar = Ph 0%
Scheme 1
The synthesis of 3-alkyl-1-aryl-4-thioxo-3,4-dihydropyrido[2,3-d]pyrimidin-2(1H)-ones (3) from
2-chloro-N-ethylpyridine-3-thiocarboxamide (2a) and N-butyl-2-chloropyridine-3-thiocarboxamide (2b)
was achieved as illustrated in Scheme 1. Thus, these thiocarboxamides (2) were treated with sodium
hydride at 0 ˚C. After the evolution of hydrogen gas had ceased, the temperature was raised to room
temperature and isocyanates were added. At this temperature the reaction mixture was stirred overnight.
Addition of the amide anion to isocyanate and intramolecular substitution of the resulting urea anion
intermediate on the 2-chloro substituent proceeded gradually. The desired products (3) were isolated after
usual workup and the subsequent purification by recrystallization. The yields are shown in Scheme 1.
Although the yields of the products (3) were generally moderate, when 2b was used, the yields of the
corresponding desired products were somewhat lower than those from 2a. It was found that the reaction
of 2a with an aliphatic isocyanate, such as n-butyl isocyanate, did not give the desired products; 2a was
recovered almost quantitatively. It was also found that 2-chloro-N-cyclohexylpyridine-3-thiocarboxamide
(2c) did not undergo the present reaction sequence and that 2c was recovered almost quantitatively after
an extended reaction time at a higher temperature. This could be attributed to the steric bulkiness of

HETEROCYCLES, Vol. 83, No. 7, 2011
1643
cyclohexyl substituent, which obstructs the addition of the respective amide anion to isocyanates.
Next, we were interested in investigating the use of 4-chloropyridine (4) for synthesizing
4-thioxo-3,4-dihydropyrido[4,3-d]pyrimidin-2(1H)-ones (6) via 4-chloro-3-lithiopyridine4 and 4-chloro-
N-ethylpyridine-3-thiocarboxamide (5) as shown in Scheme 2. The synthesis of 6 could also be achieved
under conditions similar to those described above for the preparation of 4-thioxo-3,4-dihydropyrido[2,3-
d]pyrimidin-2(1H)-ones (3). The yields of the products 6 are summarized in Scheme 2.
S
S
N
1. LDA, –78 ˚C, THF
2. RNCS, –78 ˚C
1. NaH, DMF, 0 ˚C
N
NEt
N
NHEt
2. ArNCO, rt
Cl
N
Ar
O
Cl
4
5 42%
6a Ar = Ph 74%
6b Ar = m-Tol 72%
6c Ar = 4-CF3C6H4 55%
6d Ar = 4-ClC6H4 70%
6e Ar = 1-naphthyl 62%
Scheme 2
In conclusion, we have demonstrated an efficient method for the preparation of
4-thioxo-3,4-dihydropyrido[2,3-d]pyrimidin-2(1H)-one derivatives from 2-chloropyridine using a
two-step sequence. We have applied this method to 4-chloro-N-ethylpyridine-3-thiocarboxamide to lead
to the first construction of 4-thioxo-3,4-dihydropyrido[4,3-d]pyrimidin-2(1H)-ones. The present method
may find usefulness in the ready availability of the starting materials as well as the simplicity of the
operations.
EXPERIMENTAL
The melting points were obtained on a Laboratory Devices MEL-TEMP II melting apparatus and are
1
uncorrected. IR spectra were recorded with a Shimadzu FTIR-8300 spectrophotometer. The H NMR
spectra were recorded using TMS as an internal reference with a JEOL ECP500 FT NMR spectrometer
13
operating at 500 MHz. The C NMR spectra were recorded using TMS as an internal reference with a
JEOL ECP500 FT NMR spectrometer operating at 125 MHz. Low-resolution MS spectra (EI, 70 eV)
were measured by a JEOL JMS AX505 HA spectrometer. TLC was carried out on a Merck Kieselgel 60
PF254. Column chromatography was performed using WAKO GEL C-200E. All of the organic solvents
used in this study were dried over appropriate drying agents and distilled prior to use.
Starting Materials. All chemicals used in this study were commercially available.
Typical Procedure for the Preparation of 2-Chloropyridine-3-thiocarboxamides (2) and
4-Chloro-N-ethylpyridine-3-thiocarboxamide (5). 2-Chloro-N-ethylpyridine-3-thiocarboxamide (2a).

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To a stirred solution of LDA (25 mmol), generated by the standard method, in THF (25 mL) at –78 ˚C
was added 2-chloropyridine (1) (1.1 g, 10 mmol); the mixture was stirred for 1.5 h at the same
temperature.4 Ethyl isothiocyanate (2.2 g, 25 mmol) was added and stirring was continued for an
additional 10 min before adding saturated aqueous NH4Cl. The mixture was extracted with AcOEt three
times (20 mL each), and the combined extracts was washed with brine and dried over anhydrous Na2SO4.
After evaporation of the solvent the residue was purified by column chromatography on silica gel to give
1
2a (0.94 g, 47%); a brown oil; Rf 0.29 (1:2 THF–hexane); IR (neat) 3208, 1559, 1398 cm–1; H NMR !
1.39 (t, J = 7.3 Hz, 3H), 3.85–3.91 (m, 2H), 7.29 (dd, J = 7.8, 5.0 Hz, 1H), 7.59 (br s, 1H), 7.96 (dd, J =
7.8, 2.3 Hz, 1H), 8.39 (dd, J = 5.0, 2.3 Hz, 1H). Anal. Calcd for C8H9ClN2S: C, 47.88; H, 4.52; N, 13.96.
Found: C, 47.79; H, 4.77; N, 13.87.
N-Butyl-2-chloropyridine-3-thiocarboxamide (2b): a yellow oil; Rf 0.28 (1:2 THF–hexane); IR (neat)
3207, 1557, 1398 cm–1; 1H NMR ! 1.00 (t, J = 7.3 Hz, 3H), 1.46–1.51 (m, 2H), 1.74–1.80 (m, 2H), 3.84
(q, J = 7.3 Hz, 2H), 7.29 (dd, J = 7.3, 4.6 Hz, 1H), 7.61 (br s, 1H), 7.96 (dd, J = 7.3, 1.8 Hz, 1H), 8.39 (dd,
J = 4.6, 1.8 Hz, 1H). Anal. Calcd for C10H13ClN2S: C, 52.51; H, 5.73; N, 12.25. Found: C, 52.45; H, 5.75;
N, 12.22.
2-Chloro-N-cyclohexylpyridine-3-thiocarboxamide (2c): a yellow solid; mp 192–195 ˚C
1
(hexane–AcOEt); IR (KBr) 3200, 1536, 1397 cm–1; H NMR ! 1.23–1.31 (m, 1H), 1.33–1.40 (m, 2H),
1.44–1,52 (m, 2H), 1.68–1.72 (m, 1H), 1.77–1.82 (m, 2H), 2.19–2.22 (m, 2H), 4.50–4.57 (m, 1H), 7.29
(ddd, J = 8.2, 4.6, 0.9 Hz, 1H), 7.44 (br s, 1H), 7.95 (dd, J = 8.2, 1.8 Hz, 1H), 8.38 (dd, J = 4.6, 1.8 Hz,
1H). Anal. Calcd for C12H15ClN2S: C, 56.57; H, 5.93; N, 11.00. Found: C, 56.48; H, 5.93; N, 10.97.
4-Chloro-N-ethylpyridine-3-thiocarboxamide (5): a yellow solid; mp 121–124 ˚C (hexane–THF); IR
(KBr) 3161, 1545, 1393 cm–1; 1H NMR ! 1.39 (t, J = 7.3 Hz, 3H), 3.85–3.90 (m, 2H), 7.31 (d, J = 5.5 Hz,
1H), 7.54 (br s, 1H), 8.44 (d, J = 5.5 Hz, 1H), 8.69 (s, 1H). Anal. Calcd for C8H9ClN2S: C, 47.88; H, 4.52;
N, 13.96. Found: C, 47.71; H, 4.63; N, 13.89.
Typical Procedure for the Preparation of 4-Thioxo-3,4-dihydropyrido[2,3-d]pyrimidin-2(1H)-ones
(3) or 4-Thioxo-3,4-dihydropyrido[4,3-d]pyrimidin-2(1H)-ones (6). 3-Ethyl-1-phenyl-4-thioxo-3,4-
dihydropyrido[2,3-d]pyrimidin-2(1H)-one (3a). To a stirred suspension of NaH (60% in oil; 30 mg,
0.75 mmol) in DMF (1.5 mL) at 0 ˚C was added a solution of 2a (0.15 g, 0.75 mmol) in DMF (1.5 mL).
After ceasing evolution of H2 gas the reaction temperature was raised to rt and PhNCO (89 mg, 0.75
mmol) was added; stirring was continued overnight at the same temperature. Saturated aqueous NH4Cl
(15 mL) was added and the mixture was extracted with AcOEt three times (10 mL each). The combined
extracts were washed with water three times and then brine once, dried over anhydrous Na2SO4, and
concentrated by evaporation. The residual solid was recrystallized from hexane–CH2Cl2 to afford 3a (0.12
g, 58%); a yellow solid; mp 165–167 ˚C; IR (KBr) 1703, 1583, 1330 cm–1; 1H NMR ! 1.40 (t, J = 7.3 Hz,
3H), 4.76 (q, J = 7.3 Hz, 2H), 7.19 (dd, J = 7.8, 4.6 Hz, 1H), 7.32 (dd, J = 7.8, 1.4 Hz, 2H), 7.52 (tt, J =

HETEROCYCLES, Vol. 83, No. 7, 2011
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7.3, 1.4 Hz, 1H), 7.58 (dd, J = 7.8, 7.3 Hz, 2H), 8.48 (dd, J = 4.6, 1.8 Hz, 1H), 8.96 (dd, J = 7.8, 1.8 Hz,
13
1H); C NMR ! 11.39, 44.29, 117.31, 120.01, 128.77, 129.03, 129.61, 135.80, 142.03, 148.24, 148.78,
153.91, 189.96; MS m/z 283 (100, M+). Anal. Calcd for C15H13N3OS: C, 63.58; H, 4.62; N, 14.83. Found:
C, 63.40; H, 4.69; N, 14.82.
3-Ethyl-1-(3-methylphenyl)-4-thioxo-3,4-dihydropyrido[2,3-d]pyrimidin-2(1H)-one (3b): a yellow
solid; mp 173–175 ˚C (hexane–CH2Cl2); IR (KBr) 1705, 1584, 1335 cm–1; 1H NMR ! 1.40 (t, J = 7.3 Hz,
3H), 2.44 (s, 3H), 4.75 (q, J = 7.3 Hz, 2H), 7.12 (d, J = 7.8 Hz, 1H), 7.13 (s, 1H), 7.18 (dd, J = 7.8, 4.6 Hz,
1H), 7.32 (d, J = 7.3 Hz, 1H), 7.46 (dd, J = 7.8, 7.3 Hz, 1H), 8.50 (dd, J = 4.6, 1.4 Hz, 1H), 8.96 (dd, J =
7.8, 1.4 Hz, 1H); 13C NMR ! 11.38, 21.43, 44.29, 117.28, 119.94, 125.66, 129.25, 129.40, 129.97, 135.67,
139.69, 142.01, 148.31, 148.82, 153.98, 189.96; MS m/z 297 (100, M+). Anal. Calcd for C16H15N3OS: C,
64.62; H, 5.08; N, 14.13. Found: C, 64.49; H, 5.08; N, 14.08.
1-(3-Chlorophenyl)-3-ethyl-4-thioxo-3,4-dihydropyrido[2,3-d]pyrimidin-2(1H)-one (3c): a yellow
solid; mp 164–167 ˚C (hexane–CH2Cl2); IR (KBr) 1701, 1584, 1333 cm–1; 1H NMR ! 1.39 (t, J = 7.3 Hz,
3H), 4.75 (q, J = 7.3 Hz, 2H), 7.21 (dd, J = 8.2, 4.6 Hz, 1H), 7.24 (dd, J = 7.3, 2.3, 1.8 Hz, 1H), 7.35 (t, J
= 1.8 Hz, 1H), 7.48–7.52 (m, 2H), 8.48 (dd, J = 4.6, 1.8 Hz, 1H), 8.95 (dd, J = 8.2, 1.8 Hz, 1H); 13C NMR
! 11.39, 44.30, 117.31, 120.27, 127.26, 129.36, 129.43, 130.44, 135.07, 136.77, 142.13, 147.88, 148.55,
153.83, 189.82; MS m/z 317 (100, M+). Anal. Calcd for C15H12ClN3OS: C, 56.69; H, 3.81; N, 13.22.
Found: C, 56.42; H, 3.80; N, 13.14.
3-Ethyl-1-(4-methoxyphenyl)-4-thioxo-3,4-dihydropyrido[2,3-d]pyrimidin-2(1H)-one (3d): a yellow
solid; mp 223–225 ˚C (hexane–CH2Cl2); IR (KBr) 1692, 1582, 1337 cm–1; 1H NMR ! 1.39 (t, J = 7.3 Hz,
3H), 3.87 (s, 3H), 4.76 (q, J = 7.3 Hz, 2H), 7.07 (d, J = 8.7 Hz, 2H), 7.18 (dd, J = 7.8, 4.6 Hz, 1H), 7.23
(d, J = 8.7 Hz, 2H), 8.51 (dd, J = 4.6, 1.8 Hz, 1H), 8.96 (d, J = 7.8, 1.8 Hz, 1H); 13C NMR ! 11.39, 44.34,
55.44, 114.92, 117.35, 119.94, 128.24, 129.69, 142.06, 148.50, 149.01, 153.97, 159.69, 189.95; MS m/z
313 (100, M+). Anal. Calcd for C16H15N3O2S: C, 61.32; H, 4.82; N, 13.41. Found: C, 61.08; H, 4.87; N,
13.44.
3-Ethyl-1-(naphthalen-1-yl)-4-thioxo-3,4-dihydropyrido[2,3-d]pyrimidin-2(1H)-one (3e): a yellow
solid; mp 233–236 ˚C (hexane–CH2Cl2); IR (KBr) 1697, 1585, 1337 cm–1; 1H NMR ! 1.42 (t, J = 7.3 Hz,
3H), 4.76–4.83 (m, 2H), 7.17 (dd, J = 8.2, 4.6 Hz, 1H), 7.43–7.44 (m, 2H), 7.48–7.53 (m, 2H), 7.65 (t, J =
7.8 Hz, 1H), 7.97 (d, J = 8.2 Hz, 1H), 8.02 (d, J = 8.2 Hz, 1H), 8.36 (dd, J = 4.6, 1.4 Hz, 1H), 9.00 (dd, J
13
= 8.2, 1.4 Hz, 1H); C NMR ! 11.47, 44.28, 117.21, 120.10, 121.76, 125.71, 126.49, 126.89, 127.35,
128.82, 129.77, 130.16, 132.62, 134.61, 142.06, 148.55, 148.67, 154.24, 190.14; MS m/z 333 (100, M+).
Anal. Calcd for C19H15N3OS: C, 68.45; H, 4.53; N, 12.60. Found: C, 68.32; H, 4.62; N, 12.41.
3-Butyl-1-phenyl-4-thioxo-3,4-dihydropyrido[2,3-d]pyrimidin-2(1H)-one (3f): a yellow solid; mp
1
174–176 ˚C (hexane–CH2Cl2); IR (KBr) 1705, 1583, 1333 cm–1; H NMR ! 0.97 (t, J = 7.3 Hz, 3H),
1.41–1.47 (m, 2H), 1.79–1.85 (m, 2H), 4.65–4.68 (m, 2H), 7.19 (dd, J = 8.2, 4.6 Hz, 1H), 7.31 (dd, J =

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HETEROCYCLES, Vol. 83, No. 7, 2011
7.8, 1.4 Hz, 2H), 7.51 (tt, J = 7.3, 1.4 Hz, 1H), 7.58 (dd, J = 7.8, 7.3 Hz, 2H), 8.49 (dd, J = 4.6, 1.8 Hz,
13
1H), 8.96 (dd, J = 8.2, 1.8 Hz, 1H); C NMR ! 13.70, 20.20, 28.00, 48.85, 117.34, 120.02, 128.77,
129.03, 129.62, 135.86, 142.10, 148.22, 149.02, 153.88, 190.12; MS m/z 311 (100, M+). Anal. Calcd for
C17H17N3OS: C, 65.57; H, 5.50; N, 13.49. Found: C, 65.48; H, 5.49; N, 13.41.
3-Butyl-1-(3-chlorophenyl)-4-thioxo-3,4-dihydropyrido[2,3-d]pyrimidin-2(1H)-one (3g): a yellow
solid; mp 128–130 ˚C (hexane–CH2Cl2); IR (KBr) 1709, 1584, 1331 cm–1; 1H NMR ! 0.98 (t, J = 7.3 Hz,
3H), 1.41–1.55 (m, 2H), 1.78–1.84 (m, 2H), 4.65 (t, J = 7.8 Hz, 2H), 7.19–7.24 (m, 2H), 7.34 (br s, 1H),
7.48–7.52 (m, 2H), 8.48 (dd, J = 4.6, 1.8 Hz, 1H), 8.95 (dd, J = 7.8, 1.8 Hz, 1H); 13C NMR ! 13.69, 20.18,
28.00, 48.84, 117.32, 120.27, 127.24, 129.35, 129.41, 130.44, 135.08, 136.81, 142.17, 147.85, 148.76,
153.80, 189.97; MS m/z 345 (100, M+). Anal. Calcd for C17H16ClN3OS: C, 59.04; H, 4.66; N, 12.15.
Found: C, 58.75; H, 4.75; N, 12.23.
3-Ethyl-1-phenyl-4-thioxo-3,4-dihydropyrido[4,3-d]pyrimidin-2(1H)-one (6a): a yellow solid; mp
124–127 ˚C (hexane–CH2Cl2); IR (KBr) 1705, 1587, 1352 cm–1; 1H NMR ! 1.39 (t, J = 7.3 Hz, 3H), 4.73
(q, J = 7.3 Hz, 2H), 6.38 (d, J = 5.5 Hz, 1H), 7.32 (d, J = 7.3 Hz, 2H), 7.58 (t, J = 7.3 Hz, 1H), 7.63 (t, J =
7.3 Hz, 2H), 8.47 (d, J = 5.5 Hz, 1H), 9.74 (s, 1H); 13C NMR ! 11.37, 43.66, 108.98, 117.35, 128.43,
129.98, 130.55, 135.11, 143.66, 147.67, 152.94, 155.01, 189.51; MS m/z 283 (100, M+). Anal. Calcd for
C15H13N3OS: 63.58; 4.62; 14.83. Found: C, 63.32; H, 4.74; N, 14.77.
3-Ethyl-1-(3-methylphenyl)-4-thioxo-3,4-dihydropyrido[4,3-d]pyrimidin-2(1H)-one (6b): a yellow
solid; mp 102–105 ˚C (hexane–CH2Cl2); IR (KBr) 1713, 1577, 1343 cm–1; 1H NMR ! 1.39 (t, J = 7.3 Hz,
3H), 2.45 (s, 3H), 4.73 (q, J = 7.3 Hz, 2H), 6.40 (d, J = 6.0 Hz, 1H), 7.11 (d, J = 7.8 Hz, 1H), 7.12 (s, 1H),
7.38 (d, J = 7.8 Hz, 1H), 7.50 (dd, J = 7.8, 7.3 Hz, 1H), 8.46 (d, J = 6.0 Hz, 1H), 9.73 (s, 1H); 13C NMR !
11.38, 21.33, 43.65, 109.11, 117.34, 125.27, 128.81, 130.32, 130.78, 134.99, 140.90, 143.72, 147.71,
152.93, 154.99, 189.55; MS m/z 297 (100, M+). Anal. Calcd for C16H15N3OS: 64.62; 5.08; 14.13. Found:
C, 64.54; H, 5.28; N, 14.05.
3-Ethyl-4-thioxo-1-(4-trifluoromethylphenyl)-3,4-dihydropyrido[4,3-d]pyrimidin-2(1H)-one (6c): a
yellow solid; mp 153–155 ˚C (hexane–CH2Cl2); IR (KBr) 1705, 1598, 1323 cm–1; 1H NMR ! 1.38 (t, J =
7.3 Hz, 3H), 4.72 (q, J = 7.3 Hz, 2H), 6.35 (d, J = 6.0 Hz, 1H), 7.50 (d, J = 8.2 Hz, 2H), 7.91 (d, J = 8.2
Hz, 2H), 8.50 (d, J = 6.0 Hz, 1H), 9.74 (s, 1H); 13C NMR ! 11.37, 43.70, 108.56, 117.38, 127.76, 129.08,
129.38, 132.44, 138.27, 143.06, 147.42, 153.18, 155.21, 189.29; MS m/z 351 (100, M+). Anal. Calcd for
C16H12F3N3OS: 54.70; 3.44; 11.96. Found: C, 54.53; H, 3.47; N, 11.89.
1-(4-Chlorophenyl)-3-ethyl-4-thioxo-3,4-dihydropyrido[4,3-d]pyrimidin-2(1H)-one (6d): a yellow
1
solid; mp 169–171 ˚C (MeOH); IR (KBr) 1705, 1597, 1348 cm–1; H NMR ! 1.38 (t, J = 7.3 Hz, 3H),
4.71 (q, J = 7.3 Ha, 2H), 6.39 (d, J = 6.0 Hz, 1H), 7.27 (d, J = 8.7 Hz, 2H), 7.60 (d, J = 8.7 Hz, 2H), 8.49
13
(d, J = 6.0 Hz, 1H), 9.73 (s, 1H); C NMR ! 11.37, 43.69, 108.73, 117.38, 129.93, 130.86, 133.53,
136.16, 143.38, 147.54, 153.08, 155.14, 189.37; MS m/z 317 (100, M+). Anal. Calcd for C15H12ClN3OS:

HETEROCYCLES, Vol. 83, No. 7, 2011
1647
56.69; 3.81; 13.22. Found: C, 56.65; H, 4.03; N, 13.25.
3-Ethyl-4-thioxo-1-(naphthalen-1-yl)-3,4-dihydropyrido[4,3-d]pyrimidin-2(1H)-one (6e): a yellow
solid; mp 218–220 ˚C (hexane–CH2Cl2); IR (KBr) 1705, 1593, 1350 cm–1; 1H NMR ! 1.41 (t, J = 7.3 Hz,
3H), 4.74–4.81 (m, 2H), 6.17 (d, J = 6.0 Hz, 1H), 7.46 (d, J = 8.2 Hz, 1H), 7.50–7.53 (m, 2H), 7.59 (ddd,
J = 8.2, 7.3, 1.4 Hz, 1H), 7.67 (dd, J = 8.2, 7.3 Hz, 1H), 8.01 (d, J = 8.2 Hz, 1H), 8.09 (d, J = 8.2 Hz, 1H),
13
8.37 (d, J = 6.0 Hz, 1H), 9.79 (s, 1H); C NMR ! 11.47, 43.67, 109.20, 117.35, 121.35, 125.94, 126.97,
127.19, 128.14, 129.00, 129.42, 130.67, 131.47, 134.89, 143.87, 147.64, 153.15, 155.07, 189.65; MS m/z
333 (100, M+). Anal. Calcd for C19H15N3OS: 68.45; 4.53; 12.60. Found: C, 68.18; H, 4.79; N, 12.39.
ACKNOWLEDGEMENT
The authors would like to express their sincere thanks to Mrs. Miyuki Tanmatsu of this university for
carrying out the MS experiments and performing combustion analyses.
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