Fast, microwave-promoted one-pot synthesis of bicyclic pyrimidones from Baylis-Hillman adducts

Article abstract of DOI:10.3184/174751915X14199645231447

Two types of fused pyrimidones, 3-substituted-7-chloro-4H-pyrimido[1,2-b]pyridazin-4-ones and 6-substituted-5H-thiazolo- [3,2-a]pyrimidin-5-ones were easily prepared from Baylis-Hillman adduct acetates under microwave irritation in high yields.

Full text of DOI:10.3184/174751915X14199645231447

JOURNAL OF CHEMICAL RESEARCH 2015
VOL. 39 FEBRUARY, 63–66
RESEARCH PAPER 63
Fast, microwave-promoted one-pot synthesis of bicyclic pyrimidones from
Baylis–Hillman adducts
Yongliang Liu, Kun Wan and Zengxue Wang*
Lunan Pharmaceutical Group Corporation, No. 209, Hongqi Rd, Linyi, Shandong 276005, P.R. China
Two types of fused pyrimidones, 3‑substituted‑7‑chloro‑4H‑pyrimido[1,2‑b]pyridazin‑4‑ones and 6‑substituted‑5H‑thiazolo‑
[3,2‑a]pyrimidin‑5‑ones were easily prepared from Baylis–Hillman adduct acetates under microwave irritation in high yields.
Keywords: microwave irradiation, one-pot synthesis, bicyclic pyrimidones, Baylis–Hillman adducts
The pyrimidinone framework belongs to an important class of
heterocyclic compounds possessing pharmacological properties
such as anticancer, antihypertensive, antidepressant and anti-
immune activities.1–5 Because of the remarkable medicinal
and pharmacological potential of pyrimidinone derivatives,
development of simple and efficient methodologies for the
synthesis of substituted fused pyrimidones has been and
continues to be a challenging and attractive endeavour in
organic and medicinal chemistry.
Microwave chemistry as a useful technique for a variety
of applications in organic synthesis and transformations, has
started to change the face of chemical reactions which offers
several advantages over conventional homogeneous and
heterogeneous reactions with respect to high reaction rates
and yields.6,7 The Baylis–Hillman reaction has proved to be
a powerful tool for C–C bond-forming reactions, which are
also atom economical, green and simple reaction and provide
densely functionalised molecules, The Baylis–Hillman adducts
have become valuable sources for making cyclic frameworks
containing heteroatoms.8–11 In pursuit of the interest in the
synthesis of heterocyclic molecules,12–15 we now report a one-
pot, microwave-assisted fast protocol for facile transformation
of the Baylis–Hillman adducts into bicyclic heterocyclic
frameworks containing a pyrimidone moiety.
Initially, treatment of Baylis–Hillman adduct acetate 1a and
6-chloropyridazin-3-amine 2 in refluxing toluene or acetic
acid provided the desired product 3a in 21% and 51% yields,
respectively, even prolonging the reaction time and increasing
the temperature (Table 1, entries 1–3) had little influence.
Our previous studies indicated that solvent-free conditions
may result in shortening the reaction time and improving the
yield.13,14 It was found that 81% yield of product can be obtained
when the reaction was performed at 130°C for 6 h under
solvent-free conditions (Table 1, entry 4). However, with the aid
of microwave irradiation, the reaction time could be shortened
to 1 h with a slightly high yield (Table 1, entries 5). Fortunately,
when the reaction mixture was performed in acetic acid under
microwave irradiation at 115 °C, the yield of product 3a could be
increased up to 95% within 5 minutes (Table 1, entries 6 and 7).
Encouraged by these results and the work-up operation,
and with a view to understanding the generality of this
reaction, we successfully extended the same strategy to a
series of Baylis–Hillman adduct acetates with respect to
steric and electronic effects (Table 2). As shown in Table 2,
all reactions between aryl-substituted substrates
1 and
3-amino-6-chloropyridazine 2 went smoothly to provide the
corresponding products in good to excellent yields and no
obvious electronic and steric effect were observed (Table 2,
entries 1–11). To further investigate the steric effect of the
ester moiety, the ethyl ester substrates in substrates 1 gave
lower yields and needed longer reaction times than those of
methyl ester probably due to the greater steric effect of the
former (Table 2, entries 1–4). Compared to aryl-substituted
Baylis–Hillman adducts, alkyl-substituted ones provided the
products in slightly lower yields (Table 2, entries 12 and 13).
Results and discussion
Several approaches for the synthesis of 4H-pyrimido[1,2-b]
pyridazin-4-ones 3 have been described in the literature,16–24
and the classical method for the synthesis of 4H-pyrimido[1,2-b]
pyridazin-4-ones, proposed by Svete and his co-workers, was
by treatment of appropriately substituted 3-(dimethylamino)
prop-2-enoates and 3-aminopyridazines in acetic acid.16–20
However, most of these methods suffered from some
drawbacks including difficultly accessible starting materials or
the requirement for multistep synthetic transformations.
We now report a novel and simple method for the synthesis of
compound 3 under microwave irritation from Baylis–Hillman
adduct acetates 1 (Scheme 1).
Table 1 Optimisation of the synthesis of compound 3aa
Entry
Solvent
Methodb
Temp/°C
Time
Yield /%c
1
2
3
4
5
6
7
Toluene
Acetic acid
Acetic acid
–
T
T
T
T
MW
MW
MW
reflux
reflux
reflux
130
130
90
24 h
12 h
24 h
6 h
1 h
0.5 h
5 min
21
51
52
81
86
82
95
–
Acetic acid
Acetic acid
115
Scheme 1 Synthesis of various 3‑substituted‑7‑chloro‑4H‑pyrimido[1,2‑b]
aThe reaction was carried out on Baylis–Hillman adduct acetates 1a
(2 mmol) with 6‑chloropyridazin‑3‑amine 2 (2 mmol) in solvent (10 mL) or
solvent‑free condition.
pyridazin‑4‑ones 3.
bT, traditional heating; MW, microwave irradiation (300W).
cIsolated yields based on 1a.
* Correspondent. E-mail: wangzx0912@126.com

64 JOURNAL OF CHEMICAL RESEARCH 2015
Table 2 Microwave assisted synthesis of 3 from Baylis–Hillman adducts 1a
Table 3 Microwave assisted synthesis of 5a
Entry
R1
R2
Time/min
Yield/%b
1
2
3
4
5
6
Ph
Ph
2‑ClC6H4
3‑MeOC6H4
2‑Thiophenyl
Isopentyl
Me
Et
Et
Me
Me
Me
5
15
15
5
5
10
5a 96 (92c)
5a 90 (73c)
5b 89 (65c)
5c 95 (85c)
5d 86 (65c)
5e 81 (30c)
Entry
R1
R2
Time/min
Yield/%b
1
2
3
4
5
6
7
8
9
10
11
12
13
Ph
Ph
Me
Et
Me
Et
Me
Me
Me
Me
Me
Me
Me
Me
Me
5
15
5
15
5
5
5
5
5
5
5
10
10
95 (3a)
89 (3a)
97 (3b)
91 (3b)
96 (3c)
93 (3d)
98 (3e)
96 (3f)
93 (3g)
96 (3h)
91 (3i)
83 (3j)
85 (3k)
aThe reaction was carried out on Baylis–Hillman adduct acetates 3 (2 mmol)
with thiazol‑2‑amine 5 (2 mmol) in acetic acid (10 mL).
bIsolated yield based on 3.
2‑ClC6H4
2‑ClC6H4
3‑ClC6H4
4‑ClC6H4
2‑Cl‑6‑FC6H3
3‑NO2C6H4
3‑MeOC6H4
4‑FC6H4
2‑Thiophenyl
Isopentyl
Pentyl
cThe yields given in ref. 14.
Synthesis of 3‑substituted‑7‑chloro‑4H‑pyrimido[1,2‑b]pyridazin‑4‑
ones (3) and 6‑substituted‑5H‑thiazolo[3,2‑a]pyrimidin‑5‑ones (5);
general procedure
A magnetically stirred mixture of the appropriate Baylis–Hillman
adduct acetate 1 (2 mmol) and 3-amino-6-chloropyridazine 2 or
2-aminothiazole 4 (2 mmol) was subjected to microwave irradiation
(300 W) under an atmosphere of N2 at 115 °C for 5–15 min in acetic
acid (10 mL). After cooling, the mixture was poured into ice water
(50 mL). The precipitate was filtered and washed with water
(2×10 mL) and ethanol (2×5 mL), then dried under vacuum to afford
3 or 5.
aThe reaction was carried out on Baylis–Hillman adduct acetates 1 (2 mmol)
with 6‑chloropyridazin‑3‑amine 2 (2 mmol) in acetic acid (10 mL).
bIsolated yields based on 1.
3‑Benzyl‑7‑chloro‑4H‑pyrimido[1,2-b]pyridazin‑4‑one (3a): Grey
powder; from methyl 2-[acetoxy(phenyl)methyl]acrylate to yield 3a
516 mg (95%), or from ethyl 2-[acetoxy(phenyl)methyl]acrylate to
yield 3a 484 mg (89%); m.p. 219.5–221.1 °C; IR νmax (KBr)/cm–1: 3082,
Zhong et al.14 have reported 5H-thiazolo[3,2-a]pyrimidin-
5-ones 5 could be successfully prepared in satisfactory
yields via treatment of Baylis–Hillman adduct acetate 1 and
2-aminothiazole 4 at 130 °C for 3–6 hours under solvent-
free and base-free conditions. As the starting materials were
similar, we thought the above, optimised, protocol was also
suitable for the preparation of compounds 5. To our surprise,
compared with previous work,14 the present method gave
5H-thiazolo[3,2-a]pyrimidin-5-ones 5 in dramatically shorter
reaction times and also in higher yields (Scheme 2, Table 3),
especially for those substrates where R1 is a heteroaryl or an
alkyl group (Table 3, entries 5 and 6) or R2 is an ethyl group
(Table 3, entries 2 and 3).
1
3011, 1636, 1541, 1488, 1130, 1092, 832, 766.; H NMR (400 MHz,
DMSO-d6) δH 3.76 (2H, s, CH2), 7.21–7.34 (5H, m, ArH), 7.71 (1H, d,
J=9.6 Hz, CH=CHCCl), 7.74 (1H, d, J=9.6 Hz, CH=CHCCl), 8.35
(1H, s, C=CHN); 13C NMR (100 Hz, DMSO-d6) δC 33.4, 126.3, 128.0,
128.3(2C), 128.9(2C), 130.2, 134.7, 138.5, 138.8, 145.6, 147.2, 167.1;
MS (ESI): m/z (%): 272 (M+ +1, 100). HRMS calcd for C14H10ClN3O
[M+]: 271.0512; found: 271.0509.
7‑Chloro‑3‑(2‑chlorobenzyl)‑4H‑pyrimido[1,2‑b]pyridazin‑4‑
one (3b): Grey powder; from methyl 2-[acetoxy(phenyl)methyl]
acrylate to yield 3b 594 mg (95%), or from ethyl 2-(acetoxy(phenyl)
methyl)acrylate to yield 3b 556 mg (89%); m.p. 236.4–237.1 °C;
1
IR νmax (KBr)/cm–1: 3036, 1632, 1481, 1259, 1125, 850, 741; H NMR
(400 Hz, DMSO-d6) δH 3.86 (2H, s, CH2), 7.28–7.35 (3H, m, ArH),
7.47–7.49 (1H, m, ArH), 7.74 (1H, d, J=9.6 Hz, CH=CHCCl), 7.77 (1H,
d, J=9.6 Hz, CH=CHCCl), 8.08 (1H, s, C=CHN); 13C NMR (100 Hz,
DMSO-d6) δC 31.3, 126.1, 127.2, 128.5, 129.3, 130.3, 130.9, 133.3,
134.8, 135.4, 139.1, 145.8, 147.4, 167.0; MS (ESI): m/z (%): 306 (M+ +1,
100). HRMS calcd for C14H9Cl2N3O [M+]: 305.0123; found: 305.0112.
7‑Chloro‑3‑(3‑chlorobenzyl)‑4H‑pyrimido[1,2‑b]pyridazin‑4‑one
(3c): Grey powder; yield 588 mg (96%); m.p. 230.3–231.7 °C; IR νmax
Scheme 2 Synthesis of various 5H‑thiazolo[3,2‑a]pyrimidin‑5‑ones 5.
Conclusions
1
(KBr)/cm–1: 3441, 1642, 1489, 1130, 791, 659; H NMR (400 MHz,
In conclusion, we have developed a fast and efficient method
for the synthesis of substituted fused pyrimidones from
Baylis–Hillman adducts under MW irradiation in acetic acid.
Future work will be aimed at investigating the scope of our
procedure for the synthesis of other heterocyclic systems.
DMSO-d6) δH 3.76 (2H, s, CH2), 7.25–7.28 (1H, m, ArH), 7.29–7.32
(2H, m, ArH), 7.41 (1H, t, J=0.4 Hz, ArH), 7.71 (1H, d, J=9.6 Hz,
CH=CHCCl), 7.74 (1H, d, J=9.6 Hz, CH=CHCCl), 8.51 (1H, s,
C=CHN); 13C NMR (100 Hz, DMSO-d6) δC 33.0, 126.2, 127.0, 127.6,
128.5, 130.0, 130.1, 132.8, 134.7, 139.1, 141.1, 145.6, 147.3, 167.0; MS
(ESI): m/z (%): 306 (M+ +1, 100). HRMS calcd for C14H9Cl2N3O [M+]:
305.0123; found: 305.0114.
7‑Chloro‑3‑(4‑chlorobenzyl)‑4H‑pyrimido[1,2‑b]pyridazin‑4‑
one (3d): Grey powder; yield 569 mg (93%); m.p. 234.1–235.0 °C;
IR νmax (KBr)/cm–1: 3052, 1625, 1486, 1130, 1016, 809, 657, 553;
1H NMR (400 MHz, DMSO-d6) δH 3.75 (2H, s, CH2), 7.32–7.38 (4H,
m, ArH), 7.71 (1H, d, J=9.6 Hz, CH=CHCCl), 7.74 (1H, d, J=9.6 Hz,
CH=CHCCl), 8.45 (1H, s, C=CHN); 13C NMR (100 MHz, DMSO-d6)
δC 32.7, 127.4, 128.1 (2C), 130.1, 130.7 (2C), 130.9, 134.7, 137.6, 138.9,
145.6, 147.3, 167.0; MS (ESI): m/z (%): 306 (M+ +1, 100). HRMS calcd
for C14H9Cl2N3O [M+]: 305.0123; found: 305.0112.
Experimental
Melting points were determined by Büchi B-540 melting point
1
apparatus and are uncorrected. H and 13C spectra were recorded in
DMSO-d6 or CDCl3 with tetramethylsilane (TMS, δ=0) as an internal
standard at ambient temperature on a Varian-400 MHz spectrometer
at 400 and 100 MHz. Mass spectra were obtained on a Thermo
Finnigan LCQ-Advantage spectrometer (ESI). HRMS was carried
out on an APEX (Bruker) mass III spectrometer. The Baylis–Hillman
adducts were prepared according to the literature procedure.8 All
microwave experiments were performed with the APEX Microwave
Chemistry Workstation – Excel.

JOURNAL OF CHEMICAL RESEARCH 2015 65
7‑Chloro‑3‑(2‑chloro‑6‑fluorobenzyl)‑4H‑pyrimido[1,2‑b]
pyridazin‑4‑one (3e): Off-white powder; yield 635 mg (98%); m.p.
218.6–220.0 °C; IR νmax (KBr)/cm–1: 3033, 1633, 1478, 1249, 1125, 953,
CH=CHCCl), 7.60 (1H, d, J=9.6 Hz, CH=CHCCl), 7.92 (1H, s,
C=CHN); 13C NMR (100 Hz, DMSO-d6) δC 13.9, 21.9, 26.6, 27.7, 31.0,
128.9, 130.0, 134.7, 137.9, 145.4, 146.9, 167.4; MS (ESI): m/z (%): 252
(M+ +1, 100). HRMS calcd for C12H14ClN3O [M+]: 251.0825; found:
251.0821.
6‑Benzyl‑5H‑thiazolo[3,2‑a]pyrimidin‑5‑one (5a) Pale yellow
crystals; from methyl 2-(acetoxy(phenyl)methyl)acrylate to yield
5a 465 mg (96%), from ethyl 2-(acetoxy(phenyl)methyl)acrylate to
yield 5a 436 mg (90%); m.p. 227.9–230.1 °C (lit.14 229.9–227.5 °C),
1H NMR (400 MHz, DMSO-d6) δH 3.87 (2H, s, CH2), 7.21–7.98 (6H, m,
ArH), 7.73 (1H, d, J=4.4 Hz, SCH=CHN), 8.16 (1H, s, COC=CHN);
MS(ESI): m/z (%): 243 (M+ +1, 100).
6‑(2‑Chlorobenzyl)‑5H‑thiazolo[3,2‑a]pyrimidin‑5‑one (5b):
Colourless crystals; yield 492 mg (89%); m.p. 201.7–202.5 °C (lit.14
201.5–202.2 °C); 1H NMR (400 MHz, DMSO-d6) δH 3.77 (2H, s, CH2),
7.26 (1H, d, J=4.8 Hz, NC=CHS), 7.29–7.32 (2H, m, ArH), 7.37 (1H,
dd, J1 = 3.6 H z, J2 =6.0 Hz, ArH), 7.47 (1H, dd, J1 = 3.6 H z, J2 =5.6 Hz,
ArH), 7.75 (1H, d, J=4.8 Hz, SCH=CHN), 7.99 (1H, s, COC=CHN);
MS(ESI): m/z (%): 277 (M+ +1, 100).
6‑(3‑Methoxybenzyl)‑5H‑thiazolo[3,2‑a]pyrimidin‑5‑one (5c):
Grey powder; yield 517 mg (95%); m.p. 204.1–205.1 °C (lit.14
204.0–204.8 °C); 1H NMR (400 MHz, DMSO-d6) δH 3.65 (2H, s,
CH2), 3.73 (3H, s, OCH3), 6.79 (1H, dd, J1 =2.8 Hz, J2 =8.4 Hz, ArH),
6.82 (1H, d, J=9.2 Hz, ArH), 6.87 (1H, s, ArH), 7.21 (1H, t, J=7.2 Hz,
ArH), 7.26 (1H, d, J=4.4 Hz, NCH=CHS), 7.73 (1H, d, J=4.4 Hz,
SCH=CHN), 8.13 (1H, s, COC=CHN); MS(ESI): m/z (%): 273 (M+ +1)
(100).
6‑(2‑Thienylmethyl)‑5H‑thiazolo[3,2‑a]pyrimidin‑5‑one (5d):
Grey power; yield 427 mg (86%); m.p. 192.6–193.2 °C (lit.14
192.5–193.2 °C); 1H NMR (400 MHz, DMSO-d6) δH 3.89 (2H, s, CH2),
6.96 (2H, m, NCH=CHS, SC=CH), 7.28 (1H, d, J=4.8 Hz, SCH=CH),
7.34 (1H, t, J=3.6 Hz, SCH=CH), 7.76 (1H, d, J=4.4 Hz, SCH=CHN),
8.27 (1H, s, COC=CHN); MS(ESI): m/z (%): 249 (M+ +1) (100).
6‑Isopentyl‑5H‑thiazolo[3,2‑a]pyrimidin‑5‑one (5e): Brown crystals;
yield 360 mg (81%); m.p. 145.7–146.9 °C (lit.14 145.8–146.4 °C);
1H NMR (400 MHz, CDCl3) δH 0.88 (6H, s, 2×CH3), 1.43 (2H, q,
J=8 Hz, (CH3)2CHCH2), 1.55–1.60 (1H, m, (CH3)2CH), 2.46 (2H,
t, J=8 Hz, CH2), 6.84 (1H, d, J=4.8 Hz, NCH=CHS), 7.41 (1H, d,
J=4.8 Hz, SCH=CHN), 7.86 (1H, s, COC=CHN); MS(ESI): m/z (%):
223 (M+ +1) (100).
1
852, 753, 559; H NMR (400 MHz, DMSO-d6) δH 3.90 (2H, s, CH2),
7.26–7.31 (1H, m, ArH), 7.39–7.43 (2H, m, CH=HCCl), 7.62 (1H,
s, ArH), 7.32 (1H, s, C=CHN); 13C NMR (100 MHz, DMSO-d6) δC
25.1 (d, J=3.0 Hz), 114.7 (d, J=22.8 Hz), 122.7 (d, J=18.2 Hz), 125.5
(d, J=25.8 Hz), 125.7, 129.9 (d, J=9.9 Hz), 130.4, 134.7, 134.8, 137.4,
145.9, 147.3, 161.1 (d, J=245.7 Hz), 166.7; MS (ESI): m/z (%): 324
(M+ +1, 100). HRMS calcd for C14H8Cl2FN3O [M+]: 323.0028; found:
323.0031.
7‑Chloro‑3‑(3‑nitrobenzyl)‑4H‑pyrimido[1,2‑b]pyridazin‑4‑one
(3f): Grey powder; yield 608 mg (96%); m.p. 277.2–279.1 °C; IR νmax
1
(KBr)/cm–1: 3084, 1644, 1489, 1344, 1129, 1097; H NMR (400 MHz,
DMSO-d6) δH 3.90 (2H, s, CH2), 7.59 (1H, t, J=8.0 Hz, ArH), 7.71
(1H, d, J=9.6 Hz, CH=CHCCl), 7.76 (1H, d, J=9.6 Hz, CH=CHCCl),
7.84 (1H, d, J=8.0 Hz, ArH), 8.08 (1H, dq, J1 =1.2 Hz, J2 =8.0 Hz,
ArH), 8.24 (1H, t, J=1.2 Hz, ArH), 8.63 (1H, s, C=CHN); 13C NMR
(100 MHz, DMSO-d6) δC 33.0, 121.4, 123.4, 126.6, 129.6, 130.2, 134.8,
135.8, 139.4, 140.9, 145.7, 147.4, 147.7, 167.0; MS (ESI): m/z (%): 317
(M+ +1, 100). HRMS calcd for C14H9ClN4O3 [M+]: 316.0363; found:
316.0370.
7‑Chloro‑3‑(3‑methoxybenzyl)‑4H‑pyrimido[1,2‑b]pyridazin‑4‑
one (3g): Grey powder; yield 561 mg (93%); m.p. 205.3–207.1 °C;
IR νmax (KBr)/cm–1: 3095, 1643, 1489, 1261, 1130, 1051, 817, 784;
1H NMR (400 Hz, DMSO-d6) δH 3.72 (5H, s, CH2 and OCH3), 6.78
(1H, dd, J1 = 2.8 H z, J2 =8.0 Hz, ArH), 6.89 (1H, s, ArH), 6.91 (1H, d,
J=2.8 Hz, ArH), 7.20 (1H, t, J=8.0 Hz, ArH), 7.70 (1H, d, J=9.6 Hz,
CH=CHCCl), 7.74 (1H, d, J=9.6 Hz, CH=CHCCl), 8.32 (1H, s,
C=CHN); 13C NMR (100 Hz, DMSO-d6) δC 33.3, 54.9, 111.6, 114.7,
121.1, 127.8, 129.2, 130.1, 134.7, 138.7, 139.9, 145.5, 147.1, 159.2, 167.0;
MS (ESI): m/z (%): 302 (M+ +1, 100). HRMS calcd for C15H12ClN3O2
[M+]: 301.0618; found: 301.0609.
7‑Chloro‑3‑(4‑fluorobenzyl)‑4H‑pyrimido[1,2‑b]pyridazin‑4‑one
(3h): Grey powder; yield 556 mg (96%); m.p. 237.3–239.0 °C, IR νmax
1
(KBr)/cm–1: 3087, 1642, 1493, 1209, 1129, 806, 660, 558; H NMR
(400 Hz, DMSO-d6) δH 3.74 (2H, s, CH2), 7.11 (2H, t, J=8.8 Hz, ArH),
7.38 (2H, dd, J1 = 5.6 H z, J2 =8.8 Hz, ArH), 7.70 (1H, d, J=9.6 Hz,
CH=CHCCl), 7.74 (1H, d, J=9.6 Hz, CH=CHCCl), 8.41 (1H, s,
C=CHN); 13C NMR (100 Hz, DMSO-d6) δC 32.6, 114.9 (J= 21.2 H z,
2C), 127.8, 130.2, 130.7 (J=8.3 Hz, 2C), 134.6, 134.7, 138.8, 145.6,
147.2, 160.9 (J=240.4 Hz), 167.1; MS (ESI): m/z (%): 290 (M+ +1, 100).
HRMS calcd for C14H9ClFN3O [M+]: 289.0418; found: 289.0413.
7‑Chloro‑3‑(thiophen‑2‑ylmethyl)‑4H‑pyrimido[1,2‑b]pyridazin‑
4‑one (3i): Grey powder; yield 505 mg (91%); m.p. 215.5–217.1 °C;
Electronic Supplementary Information
Spectral characterisation data (1H and 13C NMR spectra and
MS) for new compounds described in this paper are available
through: stl.publisher.ingentaconnect.com/content/stl/jcr/supp-data
1
IR νmax (KBr)/cm–1: 3082, 1641, 1490, 1133, 837; H NMR (400 Hz,
DMSO-d6) δH 3.96 (2H, s, CH2), 6.94–6.98 (2H, m, ArH), 7.34 (1H,
dd, J1 = 0.8 H z, J2 =4.8 Hz, ArH), 7.71 (1H, d, J=9.6 Hz, CH=CHCCl),
7.75 (1H, d, J=9.6 Hz, CH=CHCCl), 8.39 (1H, s, C=CHN); 13C NMR
(100 Hz, DMSO-d6) δC 27.6, 124.6, 126.1, 126.8, 127.3, 130.2, 134.7,
138.7, 140.3, 145.7, 147.2, 166.8; MS (ESI): m/z (%): 278 (M+ +1, 100).
HRMS calcd for C12H8ClN3OS [M+]: 277.0077; found: 277.0079.
7‑Chloro‑3‑isopentyl‑4H‑pyrimido[1,2‑b]pyridazin‑4‑one (3j):
Purple powder; yield 418 mg (83%); m.p. 166.6–168.2 °C; IR νmax
We thank Dr Weihui Zhong and The Instrumental Analysis
& Research Center of Zhejiang University of Technology for
structural analysis.
Received 24 September 2014; accepted 30 December 2014
Paper 1402890 doi: 10.3184/174751915X14199645231447
Published online: 13 February 2015
1
(KBr)/cm–1: 3140, 2951, 1634, 1482, 1139, 849, 657, 552; H NMR
(400 Hz, DMSO-d6) δH 0.90 (3H, s, CH3), 0.92 (3H, s, CH3), 1.40–1.46
(2H, m, CHCH2CH2), 1.52–1.59 (1H, m, CH), 2.42 (2H, t, J=7.2 Hz,
CHCH2CH2), 7.70 (1H, d, J=9.6 Hz, CH=CHCCl), 7.74 (1H, d,
J=9.6 Hz, CH=CHCCl), 8.37 (1H, s, C=CHN); 13C NMR (100 Hz,
DMSO-d6) δC 22.3 (2C), 25.7, 27.3, 36.1, 129.1, 130.0, 134.7, 137.9,
145.4, 146.9, 167.4; MS (ESI): m/z (%): 252 (M+ +1, 100). HRMS calcd
for C12H14ClN3O [M+]: 251.0825; found: 251.0819.
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