I. Cikotiene et al. / Tetrahedron 66 (2010) 251–258
257
(8H, m, N(CH2)4O), 6.13 (1H, s, CH), 6.99 (1H, s, CH), 7.43–7.46 (3H, m,
ArH), 7.89–7.93 (2H, m, ArH) ppm. 13C NMR (75 Hz, CDCl3):
48.4, 54.9, 66.6, 96.7, 100.5, 101.3, 125.8, 128.8, 130.7, 132.1, 156.6,
157.7, 160.0, 168.9 ppm. Anal. Calcd for C19H21N3O3S: C, 61.44; H,
5.70; N, 11.31. Found: C, 61.56; H, 5.91; N, 11.19.
d
¼0.97 (3H, t, J¼6.8 Hz, CH3), 1.27–1.30 (2H, m, CH2), 1.50–1.54 (2H,
d¼16.2,
m, CH2), 2.60 (3H, s, SCH3), 3.68 (2H, t, J¼6.8 Hz, OCH2), 6.55 (1H, s,
CH), 6.58 (1H, br s, NH), 6.59 (1H, s, CH), 7.19 (1H, t, J¼7.5 Hz, ArH),
7.39–7.47 (5H, m, ArH), 7.60 (2H, d, J¼7.5 Hz, ArH), 7.66–7.69 (2H, m,
ArH), ppm. 13C NMR (75 Hz, CDCl3):
d¼13.6, 14.4, 19.2, 31.6, 64.1,
85.9, 99.7, 103.2, 122.5, 125.8, 126.9, 128.9, 129.2, 129.9, 131.7, 132.1,
156.7, 156.7, 162.0, 173.9 ppm. Anal. Calcd for C24H25N3O2S: C,
68.71; H, 6.01; N, 10.02. Found: C, 68.77; H, 6.09; N, 10.11.
4.3.2. 4-Anilino-5-methoxy-2-methylthio-7-phenyl-5H-pyrano[4,3-
d]pyrimidine 3b. Yellowish solid, yield 85% (method D), 96%
(method E), mp 115–117 ꢁC. IR (KBr): nmax¼3441 (NH) cmꢂ1
.
1H
NMR (300 MHz, CDCl3):
d
¼2.56 (3H, s, SCH3), 3.61 (3H, s, OCH3),
4.3.8. 4-Amino-5-methoxy-2-methylthio-7-phenyl-5H-pyrano[4,3-
6.48 (1H, s, CH), 6.54 (1H, s, CH), 7.00 (1H, br s, NH), 7.15 (1H, t,
d]pyrimidine 3h. Yellowish solid, yield 79% (method E), mp 178–
J¼7.5 Hz, ArH), 7.39–7.49 (5H, m, ArH), 7.60 (2H, d, J¼7.5 Hz, ArH),
180 ꢁC (from MeOH). IR (KBr): nmax¼3442, 3439 (NH2) cmꢂ1
.
1H
7.82–7.83 (2H, m, ArH) ppm. 13C NMR (75 Hz, CDCl3):
99.7, 100.4, 101.3, 122.5, 125.8, 126.7, 128.8, 129.2, 129.8, 130.7, 132.1,
156.6, 157.7, 160.0, 169.9 ppm. Anal. Calcd for C21H19N3O2S: C,
66.82; H, 5.07; N, 11.13. Found: C, 66.85; H, 5.06; N, 11.27.
d
¼14.2, 56.9,
NMR (300 MHz, DMSO-d6):
d¼2.49 (3H, s, SCH3), 3.54 (3H, s, OCH3),
6.44 (1H, s, CH), 6.66 (1H, s, CH), 7.18 (2H, br s, NH2), 7.48–7.50 (3H,
m, ArH), 7.88–7.91 (2H, m, ArH) ppm. 13C NMR (75 Hz, DMSO-d6):
d
¼14.4, 55.2, 96.7, 98.1, 100.3, 126.2, 129.5, 131.1, 133.6, 154.7, 157.1,
159.9, 171.2 ppm. Anal. Calcd for C15H15N3O2S: C, 59.78; H, 5.02; N,
13.94. Found: C, 60.00; H, 5.09; N, 14.02.
4.3.3. 5-Ethoxy-2-methylthio-4-morpholin-4-yl-7-phenyl-5H-pyr-
ano[4,3-d]pyrimidine 3c. Yellowish solid, yield 88% (method E), mp
157–158 ꢁC (from 2-PrOH-octane). 1H NMR (300 MHz, CDCl3):
4.3.9. 5-Methoxy-2-methylthio-4-pyrrolidin-4-yl-7-phenyl-5H-pyr-
ano[4,3-d]pyrimidine 3i. Yellowish solid, yield 39% (method D), 89%
(method E), mp 117–118 ꢁC (from MeOH). 1H NMR (300 MHz,
d
¼1.22 (3H, t, J¼7.2 Hz, CH3), 2.56 (3H, s, SCH3), 3.53–3.60 (2H, m,
OCH2), 3.69–3.82 (8H, m, N(CH2)4O), 6.29 (1H, s, CH), 6.68 (1H, s,
CH), 7.44–7.46 (3H, m, ArH), 7.82–7.85 (2H, m, ArH) ppm. 13C NMR
CDCl3):
d
¼1.95–1.98 (4H, br s, (CH2)2), 2.51 (3H, s, SCH3), 3.55 (3H, s,
(75 Hz, CDCl3):
d
¼14.0,14.9, 48.9, 63.4, 66.7, 96.0,101.2,102.3,125.4,
OCH3), 3.60–3.67 (4H, m, N(CH2)2), 6.50 (1H, s, CH), 6.58 (1H, s, CH),
128.6, 130.1, 133.1, 156.4, 157.0, 161.4, 171.0 ppm. Anal. Calcd for
C20H23N3O3S: C, 62.32; H, 6.01; N, 10.90. Found: C, 62.51; H, 5.89; N,
11.01.
7.40–7.44 (3H, m, ArH), 7.79–7.83 (2H, m, ArH) ppm. 13C NMR
(75 Hz, CDCl3):
d
¼13.2, 25.4, 48.6, 54.1, 97.5, 98.2,101.3,125.3,128.6,
129.8, 133.2, 155.2, 155.7, 156.7, 170.4 ppm. Anal. Calcd for
C19H21N3O2S: C, 64.20; H, 5.95; N, 11.82. Found: C, 64.36; H, 5.90; N,
11.69.
4.3.4. 5-Butoxy-2-methylthio-4-morpholin-4-yl-7-phenyl-5H-pyr-
ano[4,3-d]pyrimidine 3d. Yellowish solid, yield 85% (method E), mp
134–135 ꢁC (from octane). 1H NMR (300 MHz, CDCl3):
d¼0.86 (3H, t,
4.3.10. 5-Methoxy-4-pyrrolidin-4-yl-7-phenyl-5H-pyrano[4,3-d]py-
rimidine 3j. Yellowish solid, yield 44% (method D), 82% (method E),
J¼7.2 Hz, CH3), 1.27–1.30 (2H, m, CH2), 1.50–1.54 (2H, m, CH2), 2.56
(3H, s, SCH3), 3.56–3.60 (1H, m, OCH), 3.78–3.83 (8H, m, N(CH2)4O),
4.00–4.07 (1H, m, OCH), 6.23 (1H, s, CH), 6.89 (1H, s, CH), 7.42–7.45
(3H, m, ArH), 7.86–7.89 (2H, m, ArH) ppm. 13C NMR (75 Hz, CDCl3):
mp 112–113 ꢁC (from MeOH). 1H NMR (300 MHz, CDCl3):
d¼2.02
(4H, br s, CH2CH2), 3.59 (3H, s, OCH3), 3.80 (4H, br s, N(CH2)2), 6.56
(1H, s, CH), 6.79 (1H, s, CH), 7.40–7.44 (3H, m, ArH), 7.79–7.83 (2H,
d
¼13.6, 14.9, 19.2, 31.4, 48.6, 66.7, 67.6, 95.9, 101.0, 101.9, 125.6,
m, ArH), 8.54 (1H, s, CH) ppm. 13C NMR (75 Hz, CDCl3):
53.9, 101.7, 106.4, 109.9, 126.5, 128.4, 129.6, 134.8, 150.7, 157.3, 159.6,
162.3 ppm. Anal. Calcd for C18H19N3O2: C, 69.88; H, 6.19; N, 13.58.
Found: C, 69.82; H, 6.09; N, 13.45.
d
¼25.1, 46.9,
128.6, 130.3, 132.7, 156.9, 157.1, 160.7, 170.2 ppm. Anal. Calcd for
C22H27N3O3S: C, 63.90; H, 6.58; N, 10.16. Found: C, 63.95; H, 6.44; N,
10.25.
4.3.5. 2-Methylthio-4-morpholin-4-yl-7-phenyl-5-(prop-2-ynyloxy)-
5H-pyrano[4,3-d]pyrimidine 3e. Yellow solid, yield 98% (method E),
4.3.11. 4-Benzylamino-5-methoxy-7-phenyl-5H-pyrano[4,3-d]py-
rimidine 3k. Yellowish solid, yield 87% (method D), mp 129–130 ꢁC.
mp 115–117 ꢁC. IR (KBr): nmax¼2118 (ChC) cmꢂ1
.
1H NMR
IR (KBr): nmax¼3440 (NH) cmꢂ1. 1H NMR (300 MHz, CDCl3):
¼3.55
d
(300 MHz, CDCl3):
d
¼2.56 (3H, s, SCH3), 2.60 (1H, t, J4¼2.4 Hz,
(3H, s, OCH3), 4.78 (2H, t, J¼4.5 Hz, CH2), 5.55 (1H, br s, NH), 6.42
hCH), 3.78–3.83 (8H, m, N(CH2)4O), 4.30 (1H, dd, J2¼16.2 Hz,
J4¼2.4 Hz, OCH), 4.60 (1H, dd, J2¼16.2 Hz, J4¼2.4 Hz, OCH), 6.62
(1H, s, CH), 6.72 (1H, s, CH), 7.44–7.47 (3H, m, ArH), 7.82–7.85 (2H,
(1H, s, CH), 6.57 (1H, s, CH), 7.32–7.42 (8H, m, ArH), 7.82–7.84 (2H,
m, ArH), 8.59 (1H, s, CH) ppm. 13C NMR (75 Hz, CDCl3):
96.6, 98.4, 125.5, 127.5, 128.2, 128.7, 129.3, 130.4, 138.6, 146.8, 157.3,
158.3 ppm. Anal. Calcd for C21H19N3O2: C, 73.03; H, 5.54; N, 12.17.
Found: C, 72.98; H, 5.43; N, 12.16.
d
¼44.7, 53.6,
m, ArH) ppm. 13C NMR (75 Hz, CDCl3):
77.7, 92.9, 101.5, 101.6, 125.2, 128.7, 130.2, 132.5, 155.7, 157.0, 161.4,
171.3 ppm. Anal. Calcd for C21H21N3O3S: C, 63.78; H, 5.35; N, 10.63.
Found: C, 63.87; H, 5.42; N, 10.75.
d
¼14.0, 48.8, 53.1, 66.8, 76.1,
Acknowledgements
4.3.6. 4-Anilino-5-ethoxy-2-methylthio-7-phenyl-5H-pyrano[4,3-
d]pyrimidine 3f. Yellowish solid, yield 78% (method D), mp
We thank Lithuanian State Science and Studies Foundation for
the financial support (Reg. No. T-09027; Grant No. T-67/09).
We express our gratitude to Dr. Visvaldas Kairys (University of
Madeira, Portugal) for the performing of some theoretical
calculations.
122–123 ꢁC. IR (KBr): nmax¼3442 (NH) cmꢂ1
.
1H NMR (300 MHz,
¼1.22 (3H, t, J¼7.2 Hz, CH3), 2.49 (3H, s, SCH3), 3.59–3.64
DMSO-d6):
d
(2H, m, OCH2), 6.79 (1H, s, CH), 6.91 (1H, s, CH), 7.18 (1H, t, J¼7.5 Hz,
ArH),7.39–7.47(5H, m, ArH),7.60(2H, d,J¼7.5 Hz,ArH), 7.82–7.84(2H,
m, ArH), 8.99 (1H, br s, NH) ppm. 13C NMR (75 Hz, DMSO-d6):
d¼14.2,
15.2, 58.9, 99.7, 100.2, 101.5, 122.5, 125.8, 126.7, 128.8, 129.2, 129.9,
130.7,132.1,156.7,157.7,162.0,170.9 ppm. Anal.CalcdforC22H21N3O2S:
C, 67.50; H, 5.41; N, 10.73. Found: C, 67.47; H, 5.40; N, 10.66.
References and notes
1. (a) Modern Acetylene Chemistry; Stang, P. J., Diederich, F., Eds.; VCH: Weinheim,
Germany, 1995; (b) Chemistry of Triple-Bonded Functional Groups; Patai, S., Ed.;
Wiley: New York, NY, 1994.
2. (a) Asao, N.; Nogami, T.; Takahashi, K.; Yamamoto, Y. J. Am. Chem. Soc. 2002, 124,
764; (b) Nakamura, H.; Ohtaka, M.; Yamamoto, Y. Tetrahedron Lett. 2002, 7631.
3. Patil, N. T.; Yamamoto, Y. J. Org. Chem. 2004, 69, 5193.
4.3.7. 4-Anilino-5-butoxy-2-methylthio-7-phenyl-5H-pyrano[4,3-
d]pyrimidine 3g. Yellowish solid, yield 84% (method E), mp 108–
109 ꢁC. IR (KBr): nmax¼3445 (NH) cmꢂ1. 1H NMR (300 MHz, CDCl3):