One-pot synthesis of novel spiro pyrano[2,3-d][1,3]thiazolo[3,2-a] pyrimidine derivatives

Article abstract of DOI:10.1080/00397911.2011.557850

In a one-pot synthesis, 1′-methyl-2,3″-dioxo-5″-aryl-1,2, 5a″,7″,8″,9a″-hexahydro-5″H,6″H- dispiro[indole-3,2′-pyrrolidine-3′,2″-pyrano[2,3-d][1,3] thiazolo[3,2-a]pyrimidine]-4′-carboxylic acid methyl ester was prepared via the sequential reaction of 4-aryloctahydro-pyrano[2,3-d]pyrimidine-2-thione, dimethyl acetylenedicarboxylate (DMAD), and a mixture of isatin and sarcosine. All the novel spiro compounds, in moderate yields, were characterized thoroughly by infrared, NMR, mass spectromentry, and elemental analysis together with x-ray crystallographic analysis.

Full text of DOI:10.1080/00397911.2011.557850

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One-Pot Synthesis of Novel Spiro
Pyrano[2,3-d][1,3]thiazolo[3,2-
a]pyrimidine Derivatives
Xiaofang Li a , Haochong Liu a , Aiting Zheng a , Zhikui Li a , Xianyong
Yu a & Pinggui Yi a
a Key Laboratory of Theoretical Chemistry and Molecular Simulation
of Ministry of Education, Hunan Province College Key Laboratory of
QSAR/QSPR, School of Chemistry and Chemical Engineering, Hunan
University of Science and Technology , Xiangtan , Hunan , China
Accepted author version posted online: 14 Feb 2014.Published
online: 29 Apr 2014.
To cite this article: Xiaofang Li , Haochong Liu , Aiting Zheng , Zhikui Li , Xianyong Yu & Pinggui Yi
(2014) One-Pot Synthesis of Novel Spiro Pyrano[2,3-d][1,3]thiazolo[3,2-a]pyrimidine Derivatives,
Synthetic Communications: An International Journal for Rapid Communication of Synthetic Organic
Chemistry, 44:10, 1414-1421, DOI: 10.1080/00397911.2011.557850
To link to this article: http://dx.doi.org/10.1080/00397911.2011.557850
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Synthetic Communications1, 44: 1414–1421, 2014
Copyright # Taylor & Francis Group, LLC
ISSN: 0039-7911 print=1532-2432 online
DOI: 10.1080/00397911.2011.557850
ONE-POT SYNTHESIS OF NOVEL SPIRO PYRANO[2,3-
d][1,3]THIAZOLO[3,2-a]PYRIMIDINE DERIVATIVES
Xiaofang Li, Haochong Liu, Aiting Zheng, Zhikui Li,
Xianyong Yu, and Pinggui Yi
Key Laboratory of Theoretical Chemistry and Molecular Simulation of
Ministry of Education, Hunan Province College Key Laboratory of QSAR=
QSPR, School of Chemistry and Chemical Engineering, Hunan University of
Science and Technology, Xiangtan, Hunan, China
GRAPHICAL ABSTRACT
Abstract In a one-pot synthesis, 10-methyl-2,300-dioxo-500-aryl-1,2,5a00,700,800,9a00-hexahydro-
500H,600H-dispiro[indole-3,20-pyrrolidine-30,200-pyrano[2,3-d][1,3]thiazolo[3,2-a]pyrimid-
ine]-40-carboxylic acid methyl ester was prepared via the sequential reaction of 4-aryl-
octahydro-pyrano[2,3-d]pyrimidine-2-thione, dimethyl acetylenedicarboxylate (DMAD),
and a mixture of isatin and sarcosine. All the novel spiro compounds, in moderate yields,
were characterized thoroughly by infrared, NMR, mass spectromentry, and elemental
analysis together with x-ray crystallographic analysis.
Keywords Azomethine ylide; 1,3-dipolar cycloaddition; one-pot reaction; pyrano[2,3-d]-
[1,3]thiazolo[3,2-a]pyrimidine; pyrano[2,3-d]pyrimidine
INTRODUCTION
One-pot multicomponent reactions are the processes that trigger the
conversion of three or more starting materials in a single operation without the
need to isolate intermediates. These strategies are used to improve the efficiency of
chemical reactions whereby multiple carbon–carbon and carbon–heteroatom and
stereocenters are formed.[1–3]
Received October 13, 2010.
Address correspondence to Pinggui Yi, School of Chemistry and Chemical Engineering, Hunan
University of Science and Technology, Xiangtan, Hunan 411201, China. E-mail: pgyi@hnust.edu.cn
1414

PYRANO[2,3-d][1,3]THIAZOLO[3,2-a]PYRIMIDINES
1415
Scheme 1. One-pot synthesis of novel spiro pyrano[2,3-d][1,3]thiazolo[3,2-a]pyrimidine derivativies.
Spiro oxindoles, the main synthetic strategy of which is the 1,3-dipolar cycload-
dition of azomethine ylide generated by the decarboxylative condensation of isatin
and sarcosine and exocyclic double bond, have become important synthetic targets
as these structural frameworks form the core units of many naturally occurring
molecules that possess significant biological activities such as antimicrobial,
antitumoral, and antibiotic activities and inhibit the human NK-1 receptor.[4–6]
The thiazolo[3,2-a]pyrimidine moiety represents another common skeleton present
in molecules endowed with biological properties such as antiallergic, analgesic,
sedative, and calcium antagonistic activities.[7–9] Because of the importance of
these two structural frameworks, synthesis of molecular architectures containing
both spiro-oxindole and thiazolo[3,2-a]pyrimidine could be of great biological
interest.
As a part of our ongoing research program in the area of cycloaddtion reac-
tions,[10–12] we herein first report the one-pot synthesis of a series of novel spiro
pyrano[2,3-d][1,3]thiazolo[3,2-a]pyrimidine derivatives (Scheme 1).
RESULTS AND DISCUSSION
The condensation reaction of 4-aryl-octahydro-pyrano[2,3-d]pyrimidine-2-
thione 1[13] and dimethyl acetylenedicarboxylate (DMAD) afforded intermediates
methyl-(3-oxo-5-aryl-5a,7,8,9a-tetrahydro-5H,6H-pyrano[2,3-d][1,3]thiazolo[3,2-a]-
pyrimidine-2(3H)-ylidene)acetate 20. The 1,3-dipolar cycloaddition of 20 and
azomethine ylide generated in situ from isatin and sarcosine yielded 10-methyl-2,300-
dioxo-500-aryl-1,2,5a00,700,800,9a00-hexahydro-500H,600H-dispiro[indole-3,20-pyrrolidine-
30,200-pyrano[2,3-d][1,3]thiazolo[3,2-a]pyrimidine]-40-carboxylic acid methyl ester 2 in
moderate yields (Scheme 2).
The structures of products 2a–2i were confirmed by different spectroscopic
techniques (mass spectrometry [MS], infrared [IR], and NMR) and elemental analy-
sis together with x-ray analysis. The IR spectrum of 2g exhibited three carbonyl
peaks located at 1740.2, 1719.4, and 1652.1 cmꢀ1, which were assigned to the meth-
oxycarbonyl, carbonyl group in the thiazole ring, and the carbonyl group of the pyr-
rolidine ring, respectively. Further, the mass spectrum of 2g showed a molecular ion
peak at m=z 547 ([M þ H]þ), which indicates the existence of 2g. The 1H NMR spec-
trum of 2g revealed three singlets at d 2.21, 2.30, and 3.71 resulting from N–CH3(H-
13), –CH3(H-16), and –OCH3(H-14), respectively. One doublet of doublets at d 0.96
(J ¼ 2.5, 11.5 Hz) and a doublet at d 4.50 (J ¼ 11.5 Hz) were assignable to the proton
of CH (H-4) and CH (H-5) in pyrimidine ring. Furthermore, there were a doublet at

1416
X. LI ET AL.
Scheme 2. Mechanism of the cycloaddition.
d 1.32 (J ¼ 13.5 Hz) and a multiplet at d 1.78–1.88 resulting from tetrahydropyran
ring for the protons of methylene (H-2), a triplet at d 3.69 (J ¼ 11.5 Hz), and a doub-
let of doublets at d 4.10 (J ¼ 4.5, 11.5 Hz) corresponding to methylene (H-1) in the
tetrahydropyran ring. A doublet at d 1.32 (J ¼ 13.5 Hz) was assignable to the protons
of CH2 (H-3) in the tetrahydropyran ring, and three triplets at d 3.61 (J ¼ 8.5 Hz),
4.03 (J ¼ 8.5 Hz), and 4.16 (J ¼ 8.5 Hz) resulted from –CH2(H-10) and –CH (H-11)
in the pyrrolidine ring, respectively. The presence of a doublet at d 4.95 was assign-
able to the proton of Ar-CH (H-6), and several doublets and triplets in the range of d
6.76–7.28 were for aromatic protons. The existence of a singlet downfield at d 8.43
corresponds to NH in indole ring.
The 13C NMR spectrum of the product 2g exhibits the presence of three meth-
ylene carbons that exist in the tetrahydropyran ring at d 67.97 (C-1), 20.24 (C-2), and
23.55 (C-3); the signals of three methylene carbons of CH in the pyrimidine ring at d
35.73 (C-4), 58.21 (C-5), and 78.65 (C-6); and the presence of signals at d 54.60 and
47.64 assignable to the equivalent methylene carbon (C-10) and carbon of CH (C-11)
in the pyrrolidine ring. The chemical shifts were as follows: -CH3 carbon at d 21.07
(C-16), N-CH3 carbon at d 35.70 (C-13), and -OCH3 carbon at d 52.28 (C-14). The
Figure 1. Part HMBC correlations of 2 g.

PYRANO[2,3-d][1,3]THIAZOLO[3,2-a]PYRIMIDINES
1417
Figure 2. Molecular skeleton structure of compound 2c.
three carbonyl carbons were at d 170.23 (C-15), 172.15 (C-7), and 176.20 (C-12). The
signals at d 64.81 and 80.09 are assignable for the two spiro carbons of (C-8) and (C-
1
9) respectively based on H-13C heteronuclear multiple-bond correlation (HMBC)
(Figure 1). Further, the structure of the product was confirmed by x-ray diffraction
analysis of 2c14(Fig. 2).
The molecular structure of 2c contains two spiro junctions, which consist of a
planar 2-oxindole ring, a pyrrolidine ring, and a pyrano[2,3-d][1,3]thiazolo[3,2-
a]pyrimidine ring. The tetrahydropyrimidine ring and pyrrolidine ring adopt envel-
ope conformations, and the tetrahydropyran ring has a chair conformation.
EXPERIMENTAL
Materials and Instruments
4-Aryl-octahydro-pyrano[2,3-d]pyrimidine-2-thione 1[13] was prepared accord-
ing to the reported procedures. All NMR spectra were recorded on a Bruker AV-II
1
500-MHz NMR spectrometer, operating at 500 MHz for H and 125 MHz for 13C.
1
Tetramethylsilane (TMS) was used as an internal reference for H and 13C chemical
shifts. CDCl3 was used as solvent. Elemental analysis was measured by an Elementar
Analyzer (Vario EL II). Mass spectra (MS) were measured on a Finnigan LCQ
Advantage MAX mass spectrometer; IR spectra were recorded on a Perkin-Elmer
spectrometer (Spectrum One). Melting points were measure by a Yanaco MP500
melting-point apparatus and were uncorrected.
Crystal Structure Determination
The white prismatic crystal of 2c was subjected to x-ray structural analysis
˚
˚
and the orthorhombic space group Pbca with a ¼ 8.9414(18) A, b ¼ 15.596(3) A,
3
ꢁ
ꢁ
ꢁ
˚
˚
c ¼ 39.017(8) A, a ¼ 90.00 , b ¼ 90.00 , c ¼ 90.00 , V ¼ 5440.8(19) A , Z ¼ 8, and
q ¼ 1.469 g=cm3. Final R and wR (on F2) were 0.0573 and 0.1477 for 5761 reflec-
tions. The crystallographic data is available from the Cambridge Crystallographic
Data Centre, CCDC number CCDC 796436.[14]

1418
X. LI ET AL.
1’-Methyl-2,300-dioxo-500-aryl-1,2,5a00,700,800,9a00-hexahydro-500H,600H-
dispiro[Indole-3,2’-pyrrolidine-3’,200-pyrano[2,3-d][1,3]thiazolo[3,2-
a]pyrimidine]-4’-carboxylic Acid Methyl Ester (2a–2i)
General procedure for the synthesis. A mixture of 1 (1 mmol) and DMAD
(1 mmol) in methanol (40 mL) was heated to reflux for 3 h, isatin (1 mmol) and sarco-
sine (1 mmol) were added, and the resulting solution were further refluxed for 12 h.
After completion of the reaction as evident from thin-layer chromatography (TLC),
the solvent was evaporated in vacuum. The residue was purified by column chroma-
tography employing petroleum ether=ethyl acetate mixture (4:1, V=V) as eluent to
obtain 2.
500-(4-Chlorophenyl)-1’-methyl-2,300-dioxo-1,2,5a00,700,800,9a00-hexahydro-
500H,600H-dispiro[indole-3,2’-pyrrolidine-3’,200-pyrano[2,3-d][1,3]thiazolo[3,2-a]-
pyrimidine]-4’-carboxylic acid methyl ester (2a). White solid, yield 60%, mp
1
239–240 ꢁC; IR (KBr) v: 1736.2, 1719.9, 1634.2 cmꢀ1; H NMR (CDCl3, 500 MHz)
d: 0.92 (d, J ¼ 11.0 Hz, 1H), 1.35 (d, J ¼ 13.5 Hz, 1H), 1.46–1.56 (m, 2H), 1.75–
1.81 (m, 1H), 2.21 (s, 3H), 3.64 (t, J ¼ 8.5 Hz, 1H), 3.70 (t, J ¼ 11.5 Hz, 1H), 3.75
(s, 3H), 4.01 (t, J ¼ 8.5 Hz, 1H), 4.10–4.16 (m, 2H), 4.53 (d, J ¼ 11.5 Hz, 1H), 4.96
(d, J ¼ 2.0 Hz, 1H), 6.81 (d, J ¼ 8.5 Hz, 2H), 6.91 (d, J ¼ 8.0 Hz, 1H), 6.98 (t,
J ¼ 7.5 Hz, 1H), 7.16 (d, J ¼ 7.5 Hz, 1H), 7.24–7.26 (m, 2H), 7.31 (t, J ¼ 7.5 Hz,
1H), 8.32 (s, 1H); 13C NMR (CDCl3, 125 MHz) d: 20.23, 23.46, 35.69, 35.89,
47.56, 52.33, 54.62, 57.85, 64.79, 67.99, 78.52, 80.06, 110.28, 122.32, 123.30,
125.74, 128.56, 128.84, 130.62, 133.17, 140.31, 143.35, 148.91, 170.24, 172.07,
176.12; ESI MS m=z: 567 [M þ H]þ. Anal. Calcd. for C28H27ClN4O5S: C, 59.31;
H, 4.80; N, 9.88. Found: C, 59.18; H, 5.03; N, 9.72.
500-(4-Methoxyphenyl)-1’-methyl-2,300-dioxo-1,2,5a00,700,800,9a00-hexahydro-
500H,600H-dispiro[indole-3,2’-pyrrolidine-3’,200-pyrano[2,3-d][1,3]thiazolo[3,2-a]-
pyrimidine]-4’-carboxylic acid methyl ester (2b). White solid, yield 55%, mp
1
208–209 ꢁC; IR (KBr) v: 1730.9, 1719.5, 1651.7 cmꢀ1; H NMR (CDCl3, 500 MHz)
d: 0.95 (dd, J1 ¼ 2.0 Hz, J2 ¼ 11.5 Hz, 1H), 1.33 (d, J ¼ 8.5 Hz, 1H), 1.49–1.51 (m,
2H), 1.77–1.81 (m, 1H), 2.21 (s, 3H), 3.61 (t, J ¼ 8.5 Hz, 1H), 3.70 (t, J ¼ 12.0 Hz,
1H), 3.75 (s, 3H), 3.77 (s, 3H), 4.03 (t, J ¼ 8.5 Hz, 1H), 4.09–4.12 (m, 1H), 4.16
(t, J ¼ 8.5 Hz, 1H), 4.50 (d, J ¼ 11.5 Hz, 1H), 4.95 (d, J ¼ 2.0 Hz, 1H), 6.80 (d,
J ¼ 8.5 Hz, 4H), 6.87 (d, J ¼ 8.0 Hz, 1H), 6.97 (t, J ¼ 7.5 Hz, 1H), 7.17 (d, J ¼ 7.5 Hz,
1H), 7.30 (t, J ¼ 7.5 Hz, 1H), 8.46 (s, 1H); 13C NMR (CDCl3, 125 MHz) d: 20.23,
23.53, 35.69, 35.81, 47.69, 52.27, 54.58, 55.25, 57.87, 64.80, 67.97, 78.68, 80.08,
110.32, 113.80, 122.23, 123.29, 125.68, 128.47, 130.56, 133.82, 143.38, 148.11,
158.86, 170.23, 172.14, 176.20; ESI MS m=z: 563 [M þ H]þ. Anal. Calcd. for
C29H30N4O6S: C, 61.91; H, 5.37; N, 9.96. Found: C, 61.64; H, 5.61; N, 10.17.
500-(2,4-Dichlorophenyl)-1’-methyl-2,300-dioxo-1,2,5a00,700,800,9a00-hexahydro-
500H,600H-dispiro[indole-3,2’-pyrrolidine-3’,200-pyrano[2,3-d][1,3]thiazolo[3,2-a]-
pyrimidine]-4’-carboxylic acid methyl ester (2c). White solid, yield 62%, mp
1
233–234 ꢁC; IR (KBr) v: 1740.3, 1719.5, 1648.9 cmꢀ1; H NMR (CDCl3, 500 MHz)
d: 0.96 (d, J ¼ 9.0 Hz, 1H), 1.40 (d, J ¼ 13.5 Hz, 2H), 1.51–1.57 (m, 1H), 2.00
(s, 1H), 2.19 (s, 3H), 3.67 (d, J ¼ 11.0 Hz, 2H), 3.75 (s, 3H), 4.00 (t, J ¼ 8.5 Hz,
1H), 4.09–4.17 (m, 2H), 4.96 (s, 1H), 5.09 (d, J ¼ 11.0 Hz, 1H), 6.37 (d, J ¼ 8.0 Hz,

PYRANO[2,3-d][1,3]THIAZOLO[3,2-a]PYRIMIDINES
1419
1H), 6.98 (t, J ¼ 7.5 Hz, 2H), 7.15 (d, J ¼ 7.5 Hz, 2H), 7.29 (d, J ¼ 8.0 Hz, 2H), 8.67
(s, 1H); 13C NMR (CDCl3, 125 MHz) d: 20.92, 23.37, 35.76, 36.63, 47.34, 52.40,
54.32, 54.67, 64.73, 67.98, 78.43, 80.15, 110.44, 122.38, 13.38, 125.73, 127.78,
128.62, 130.24, 130.67, 133.58, 134.10, 170.34, 172.05, 176.38; ESI MS m=z: 601
[M þ H]þ. Anal. Calcd. for C28H26Cl2N4O5S: C, 55.91; H, 4.36; N, 9.31. Found:
C, 55.80; H, 4.49; N, 9.19.
1’-Methyl-2,300-dioxo-500-(3,4,5-trimethoxyphenyl)-1,2,5a00,700,800,9a00-hexa-
hydro-500H,600H-dispiro[indole-3,2’-pyrrolidine-3’,200-pyrano[2,3-d][1,3]thiazolo-
[3,2-a]pyrimidine]-4’-carboxylic acid methyl ester (2d).ꢀW1 hite solid, yield 58%,
mp 209–210 ꢁC; IR (KBr) v: 1740.2, 1719.4, 1652.1 cm
;
1H NMR (CDCl3,
500 MHz) d: 1.01 (d, J ¼ 11.5 Hz, 1H), 1.35 (d, J ¼ 13.0 Hz, 1H), 1.53–1.56 (m, 2H),
1.76–1.80 (m, 1H), 2.21 (s, 3H), 3.64 (t, J ¼ 9.0 Hz, 1H), 3.67–3.72 (m, 1H), 3.75 (s,
3H), 3.79 (s, 3H), 3.83 (s, 6H), 3.99 (t, J ¼ 8.5 Hz, 1H), 4.11–4.16 (m, 2H), 4.48 (d,
J ¼ 11.5 Hz, 1H), 4.98 (d, J ¼ 2.0 Hz, 1H), 6.13 (s, 2H), 6.83 (d, J ¼ 7.5 Hz, 1H),
7.01 (t, J ¼ 7.5 Hz, 1H), 7.19 (d, J ¼ 7.5 Hz, 1H), 7.28 (t, J ¼ 7.5 Hz, 1H), 8.58 (s,
1H); 13C NMR (CDCl3, 125 MHz) d: 20.25, 23.60, 35.28, 35.66, 47.51, 52.28,
54.59, 56.08, 58.73, 60.74, 64.58, 67.95, 78.75, 80.01, 104.41, 110.03, 122.23, 123.36,
125.72, 130.40, 137.21, 137.25, 143.56, 148.49, 153.17, 170.23, 172.16, 176.14; ESI
MS m=z: 623 [M þ H]þ. Anal. calcd. for C31H34N4O8S: C, 59.79; H, 5.50; N, 9.00.
Found: C, 59.88; H, 5.30; N, 9.12.
500-(4-Fluorophenyl)-1’-methyl-2,300-dioxo-1,2,5a00,700,800,9a00-hexahydro-
500H,600H-dispiro[indole-3,2’-pyrrolidine-3’,200-pyrano[2,3-d][1,3]thiazolo[3,2-a]-
pyrimidine]-4’-carboxylic acid methyl ester (2e). White solid, yield 67%, mp
1
225–226 ꢁC; IR (KBr) v: 1741.1, 1719.1, 1651.7 cmꢀ1; H NMR (CDCl3, 500 MHz)
d: 0.94 (d, J ¼ 11.5 Hz, 1H), 1.35 (d, J ¼ 13.5 Hz, 1H), 1.45–1.56 (m, 2H), 1.75–
1.81 (m, 1H), 2.21 (s, 3H), 3.63 (t, J ¼ 9.0 Hz, 1H), 3.71 (t, J ¼ 11.0 Hz, 1H), 3.75
(s, 3H), 4.01 (t, J ¼ 8.5 Hz, 1H), 4.01–4.17 (m, 2H), 4.54 (d, J ¼ 11.5 Hz, 1H), 4.96
(d, J ¼ 2.0 Hz, 1H), 6.85 (dd, J1 ¼ 5.5 Hz, J2 ¼ 8.5 Hz, 2H), 6.91–7.00 (m, 4H), 7.17
(d, J ¼ 7.5 Hz, 1H), 7.30 (t, J ¼ 7.5 Hz, 1H), 8.47 (s, 1H); 13C NMR (CDCl3,
125 MHz) d: 20.21, 23.46, 35.68, 35.94, 47.61, 52.31, 54.59, 57.77, 64.77, 67.97,
78.58, 80.05, 110.33, 115.18, 115.35, 122.28, 123.27, 125.70, 128.97, 129.03, 130.60,
137.49, 137.51, 143.40, 148.72, 161.07, 163.03, 170.25, 172.09, 176.18; ESI MS m=
z: 551 [M þ H]þ. Anal. calcd. for C28H27FN4O5S: C, 61.08; H, 4.94; N, 10.18.
Found: C, 61.00; H, 4.83; N, 10.40.
1’-Methyl-500-[4-(methylthio)phenyl]-2,300-dioxo-1,2,5a00,700,800,9a00-hexa-
hydro-500H,600H-dispiro[indole-3,2’-pyrrolidine-3’,200-pyrano[2,3-d][1,3]thiazolo-
[3,2-a]pyrimidine]-4’-carboxylic acid methyl ester (2f). ꢀW1 hite solid, yield 65%,
mp 207–208 ꢁC; IR (KBr) v: 1732.1, 1727.4, 1652.0 cm
;
1H NMR (CDCl3,
500 MHz) d: 0.94 (dd, J1 ¼ 2.0 Hz, J2 ¼ 11.0 Hz, 1H), 1.34 (d, J ¼ 13.5 Hz, 1H),
1.50 (d, J ¼ 4.0 Hz, 2H), 1.77–1.82 (m, 1H), 2.21 (s, 3H), 2.45 (s, 3H), 3.62 (t,
J ¼ 9.0 Hz, 1H), 3.70 (t, J ¼ 11.5 Hz, 1H), 3.75 (s, 3H), 4.02 (t, J ¼ 8.5 Hz, 1H),
4.09–4.12 (m, 2H), 4.50 (d, J ¼ 11.5 Hz, 1H), 4.95 (d, J ¼ 2.0 Hz, 1H), 6.79 (d,
J ¼ 8.0 Hz, 2H), 6.88 (d, J ¼ 8.0 Hz, 1H), 6.97 (t, J ¼ 7.5 Hz, 1H), 7.17 (d, J ¼ 8.0 Hz,
Hz, 3H), 7.30 (t, J ¼ 7.5 Hz, 1H), 8.38 (s, 1H); 13C NMR (CDCl3, 125 MHz) d: 15.97,
20.23, 23.50, 35.68, 35.74, 47.57, 52.30, 54.60, 58.03, 64.79, 67.97, 78.58, 80.07,

1420
X. LI ET AL.
110.29, 122.27, 123.28, 125.68, 126.76, 127.94, 130.60, 137.47, 138.66, 143.34, 148.51,
170.22, 172.10, 176.15; ESI MS m=z: 579 [M þ H]þ. Anal. calcd. for C29H30N4O5S2:
C, 60.19; H, 5.23; N, 9.68. Found: C, 60.01; H, 4.99; N, 9.78.
1’-Methyl-500-(4-methylphenyl)-2,300-dioxo-1,2,5a00,700,800,9a00-hexahydro-
500H,600H-dispiro[indole-3,2’-pyrrolidine-3’,200-pyrano[2,3-d][1,3]thiazolo[3,2-a]-
pyrimidine]-4’-carboxylic acid methyl ester (2g). White solid, yield 70%, mp
1
227–228 ꢁC; IR (KBr) v: 1740.2, 1719.4, 1652.1 cmꢀ1; H NMR (CDCl3, 500 MHz)
d: 0.96 (dd, J1 ¼ 2.5 Hz, J2 ¼ 11.5 Hz, 1H), 1.32 (d, J ¼ 13.5 Hz, 1H), 1.50 (d,
J ¼ 4.0 Hz, 2H), 1.78–1.88 (m, 1H), 2.21 (s, 3H), 2.30 (s, 3H), 3.61 (t, J ¼ 8.5 Hz,
1H), 3.69 (t, J ¼ 11.5 Hz, 1H), 3.71 (s, 3H), 4.03 (t, J ¼ 8.5 Hz, 1H), 4.10 (dd,
J1 ¼ 4.5 Hz, J2 ¼ 11.5 Hz, 1H), 4.16 (t, J ¼ 8.5 Hz, 1H), 4.50 (d, J ¼ 11.5 Hz, 1H),
4.95 (d, J ¼ 2.0 Hz, 1H), 6.76 (d, J ¼ 8.0 Hz, 2H), 6.85 (d, J ¼ 7.5 Hz, 1H), 6.96 (t,
J ¼ 7.5 Hz, 1H), 7.08 (d, J ¼ 7.5 Hz, 2H), 7.16 (d, J ¼ 7.5 Hz, 1H), 7.28 (d, J ¼ 9.0 Hz,
1H), 8.43 (s, 1H); 13C NMR (CDCl3, 125 MHz) d: 20.24, 21.07, 23.55, 35.70, 35.73,
47.64, 52.28, 54.60, 58.21, 64.81, 67.97, 78.65, 80.09, 110.32, 122.22, 123.29, 125.65,
127.33, 129.06, 130.55, 137.03, 138.68, 143.37, 148.15, 170.23, 172.15, 176.20; ESI
MS m=z: 547 [M þ H]þ. Anal. calcd. for C29H30N4O5S: C, 63.72; H, 5.53; N,
10.25. Found: C, 63.61; H, 5.40; N, 10.47.
500-[4-(Methoxycarbonyl)phenyl]-1’-methyl-2,300-dioxo-1,2,5a00,700,800,9a00-
hexahydro-500H,600H-dispiro[indole-3,2’-pyrrolidine-3’,200-pyrano[2,3-d][1,3]-
thiazolo[3,2-a]pyrimidine]-4’-carboxylic acid methyl ester (2h). White solid,
yield 58%, mp 224–225 ꢁC; IR (KBr) v: 1725.1, 1719.8, 1654.6 cmꢀ1 1H NMR
;
(CDCl3, 500 MHz) d: 0.96 (d, J ¼ 11.0 Hz, 1H), 1.39 (d, J ¼ 13.5 Hz, 1H), 1.45–
1.57 (m, 2H), 1.83–1.85 (m, 1H), 2.24 (s, 3H), 3.67 (t, J ¼ 9.0 Hz, 1H), 3.73 (s,
1H), 3.78 (s, 3H), 3.92 (s, 3H), 4.02 (t, J ¼ 8.5 Hz, 1H), 4.14–4.18 (m, 2H), 4.62 (d,
J ¼ 11.5 Hz, 1H), 4.98 (d, J ¼ 2.0 Hz, 1H), 6.94–7.01 (m, 4H), 7.18 (d, J ¼ 7.5 Hz,
1H), 7.34 (t, J ¼ 7.5 Hz, 1H), 7.97 (d, J ¼ 8.0 Hz, 2H), 8.05 (s, 1H); 13C NMR
(CDCl3, 125 MHz) d: 20.25, 23.45, 35.69, 35.89, 47.37, 52.13, 52.35, 54.69, 58.24,
64.77, 68.02, 78.47, 80.06, 110.25, 122.35, 123.32, 125.74, 127.56, 129.30, 129.76,
130.20, 143.27, 147.04, 149.12, 166.83, 170.25, 172.04, 175.93; ESI MS m=z: 591
[M þ H]þ. Anal. calcd. for C30H30N4O7S: C, 61.00; H, 5.12; N, 9.49. Found: C,
60.93; H, 5.29; N, 9.25.
1’-Methyl-2,300-dioxo-500-phenyl-1,2,5a00,700,800,9a00-hexahydro-500H,600H-di-
spiro[indole-3,2’-pyrrolidine-3’,200-pyrano[2,3-d][1,3]thiazolo[3,2-a]pyrimidine]-
4’-carboxylic acid methyl ester (2i). White solid, yield 65%, mp 208–209 ꢁC; IR
1
(KBr) v: 1748.0, 1727.8, 1715.4, 1643.2 cmꢀ1; H NMR (CDCl3, 500 MHz) d: 0.97
(d, J ¼ 10.0 Hz, 1H), 1.34 (d, J ¼ 13.5 Hz, 1H), 1.50 (d, J ¼ 4.0 Hz, 2H), 1.80–1.82
(m, 1H), 2.22 (s, 3H), 3.63 (t, J ¼ 8.5 Hz, 1H), 3.72 (t, J ¼ 7.5 Hz, 1H), 3.75 (s,
3H), 4.02 (t, J ¼ 9.0 Hz, 1H), 4.10–4.17 (m, 2H), 4.54 (d, J ¼ 11.0 Hz, 1H), 4.96 (d,
J ¼ 2.0 Hz, 1H), 6.87 (d, J ¼ 6.5 Hz, 3H), 6.97 (t, J ¼ 7.5 Hz, 1H), 7.17 (d, J ¼ 7.5 Hz,
1H), 7.16–7.24 (m, 1H), 7.28–7.31 (m, 3H), 8.20 (s, 1H); 13C NMR (CDCl3,
125 MHz) d: 20.32, 23.57, 35.75, 35.85, 47.67, 52.34, 54.67, 58.56, 64.87, 68.04,
78.71, 80.15, 110.40, 122.27, 123.32, 125.69, 127.52, 128.47, 130.66, 141.73, 143.47,
148.51, 170.31, 172.20, 176.24; ESI MS m=z: 533 [M þ H]þ. Anal. Calcd. for
C28H28N4O5S: C, 63.14; H, 5.30; N, 10.52. Found: C, 63.29; H, 5.16; N, 10.88.

PYRANO[2,3-d][1,3]THIAZOLO[3,2-a]PYRIMIDINES
1421
FUNDING
This research was supported by National Natural Science Foundation of
China (No. 21371054), the Key Project of Chinese Ministry of Education.(No.
210146), and Scientific Research Fund of Hunan Provincial Education Department
(09B032, 09K081).
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