354
I. Kumar et al. / Tetrahedron: Asymmetry 21 (2010) 352–355
MeO2C
CO2Me
N
N
O
O
O
O
N3
(b)
(d)
(e)
complex reaction
mixture
N
OH
(a)
OH
O
O
Ref. 14
L-(+)-
Tartaric acid
OH
OH
21
22
23
(c)
MeO2C
CO2Me
19
20
O
O
N3
N3
N
N
N
(e)
O
O
complex
reaction mixture
N
N
N
CO2Me
MeO2C
24
Scheme 4. Reagents and conditions: (a) NaH (1.1 equiv), dry THF, TsCl (1.2 equiv), 0 °C, 2 h; (ii) NaN3 (2.2 equiv), 1,4-dioxane/DMSO (10:1), 65 °C, 6 h, 81% after two steps; (b)
dimethylacetylene dicarboxylate 11 (1.1 equiv), H2O (8 mL), 70 °C, 1 h, 79%; (c) (i) NaH (2.2 equiv), TsCl (2.2 equiv), dry THF, 0 °C, 2 h; (ii) NaN3 (3.5 equiv), 1,4-dioxane/DMSO
(10:1), 65 °C, 6 h, 89%; (d) dimethylacetylene dicarboxylate 11 (2.2 equiv), H2O (8 mL), 70 °C, 1 h, 95%; (e) (i) 1 M HCl, MeOH, benzene, reflux, 4 h; (ii) CF3CO2H (0.1 equiv),
MeOH, reflux, 4 h; (iii) p-TSA (cat.), MeOH, reflux, 2 h, complex reaction mixtures in all cases.
under reduced pressure to provide a pasty mass, which was passed
through a small pad of silica gel to give slightly yellowish compound
12 (solidify slowly) in 89% yield. 1H NMR (200 MHz, CDCl3/D2O):
d = 3.81 (s, 3H), 3.98ꢀ4.15 (m, 5H), 4.84 (m, 1H), 7.15ꢀ7.21 (m,
5H). 13C NMR (75 MHz, CDCl3): d = 51.17, 52.41, 62.54, 76.31,
126.89, 127.11, 128.81, 128.98, 129.23, 139.51, 161.15, 163.92.
LC–MS (ESI-TOF): m/z [M+H]+ 306.21, [M+Na]+ 328.82.
d = 26.67, 26.87, 51.63, 61.62, 76.07, 78.31, 109.70. LC–MS (ESI-
TOF): m/z [M+H]+ 187.18, [M+Na]+ 210.17.
4.7. (4S,5S)-4,5-Bis(azidomethyl)-2,4-dimethyl-1,3-dioxalane 22
89% from 20; For 22: ½a D25
ꢁ
¼ ꢀ114:95 (c 1, CHCl3), 1H NMR
(200 MHz, CDCl3/D2O): d = 1.44 (s, 6H), 3.31 (dd, J = 4.7 Hz, 2H),
3.53 (dd, J = 3.8 Hz, 2H), 4.00ꢀ4.05 (m, 2H). 13C NMR (75 MHz,
CDCl3): d = 26.81, 51.56, 76.88, 110.33. Anal. Calcd for C7H12N6O2:
C, 39.62; H, 5.70; N, 39.60. Found: C, 39.59; H, 5.73; N, 39.69.
4.3. Methyl 4-oxo-6-phenyl-6,7-dihydro-4H-[1,2,3]triazolo[5,1-
c][1,4]oxazine-3-carboxylate 13
67% from 12; For 13: 1H NMR (200 MHz, CDCl3/D2O): d = 3.91
(s, 3H), 4.32ꢀ4.38 (m, 2H), 4.98ꢀ5.10 (m, 1H), 7.27ꢀ7.42 (m, 5H).
13C NMR (75 MHz, CDCl3): d = 52.43, 62.91, 79.13, 121.71, 124.83,
127.73, 128.19, 128.95, 139.94, 162.14, 168.12. Anal. Calcd for
C13H11N3O4: C, 57.14; H, 4.06; N, 15.38. Found: C, 57.19; H, 4.11;
N, 15.31.
4.8. Dimethyl 1-(((4S,5S)-5-(hydroxymethyl)-2,2-dimethyl-1,3-
dioxolan-4-yl)methyl)-1H-1,2,3-triazole-4,5-dicarboxylate 23
79% from 21; For 23: ½a D25
ꢁ
¼ ꢀ34:55 (c 1, CHCl3), 1H NMR
(200 MHz, CDCl3/D2O): d = 1.41 (s, 3H), 1.45 (s, 3H), 3.61ꢀ3.68 (m,
2H), 3.72ꢀ4.02 (m, 8H), 4.35ꢀ4.55 (dd, J = 3.7 Hz, 2H). 13C NMR
(75 MHz, CDCl3): d = 26.65, 26.77, 51.83, 54.29, 56.32, 61.79, 76.16,
78.28, 110.05, 129.51, 132.45, 159.19, 163.32. LC–MS (ESI-TOF):
m/z [M+H]+ 329.38, [M+Na]+ 352.46.
4.4. (S)-Dimethyl 1-((2,2-dimethyl-1,3-dioxolan-4-yl)methyl)-
1H-1,2,3-triazole-4,5-dicarboxylate 17
4.9. Tetramethyl 1,10-((4S,5S)-2,2-dimethyl-1,3-dioxolane-4,5-
diyl)bis(methylene)bis(1H-1,2,3-triazole-4,5-dicarboxylate) 24
96% from 16; For 17: ½a D25
ꢁ
¼ þ11:2 (c 1.0, CHCl3), 1H NMR
(200 MHz, CDCl3): d = 1.45 (s, 3H), 1.49 (s, 3H), 3.87 (s, 3H), 3.92–
4.15 (m, 5H), 4.18–4.25 (m, 3H). 13C NMR (75 MHz, CDCl3): d =
24.38, 25.97, 52.23, 54.69, 57.42, 69.59, 78.91, 109.13, 121.23,
122.95, 154.76, 164.23. Anal. Calcd for C12H17N3O6: C, 48.16; H,
5.73; N, 14.04. Found: C, 48.10; H, 5.65; N, 14.12.
95% from 22; For 24: ½a D25
ꢁ
¼ ꢀ46:9 (c 0.5, CHCl3), 1H NMR
(200 MHz, CDCl3/D2O): d = 1.03 (s, 6H), 3.89 (s, 6H), 3.91 (s, 6H),
3.96 (m, 2H), 4.78 (dd, J = 3.9 Hz, 2H), 4.96 (dd, J = 3.3 Hz, 2H).
13C NMR (75 MHz, CDCl3): d = 26.12, 49.31, 52.53, 53.24, 74.97,
110.66, 131.66, 139.46, 158.76, 160.02. Anal. Calcd for C19H24
N6O10: C, 45.97; H, 4.87; N, 16.93. Found: C, 45.91; H, 4.84; N,
16.98.
4.5. (S)-Methyl 6-(hydroxymethyl)-4-oxo-6,7-dihydro-4H-
[1,2,3]triazolo[5,1-c][1,4]oxazine-3-carboxylate 18
61% from 17; For 18: ½a D25
ꢁ
¼ þ5:7 (c 0.75, CHCl3), 1H NMR (200
Acknowledgement
MHz, CDCl3/D2O): d = 3.95 (s, 3H), 4.12–4.35 (m, 4H), 4.51ꢀ4.63
(m, 1H). 13C NMR (75 MHz, CDCl3): d = 52.34, 59.81, 69.95, 80.05,
123.56, 126.93, 162.12, 167.23. LC–MS (ESI-TOF): m/z [M+H]+
228.26, [M+Na]+ 150.85. Anal. Calcd for C8H9N3O5: C, 42.30; H,
3.99; N, 18.50. Found: C, 42.26; H, 4.89; N, 18.59.
Indresh Kumar thanks CSIR, New Delhi, for the award of senior
research fellowship.
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Chem. 2000, 37, 669.
4.6. ((4S,5S)-5-(Azidomethyl)-2,2-dimethyl-1,3-dioxolan-4-
yl)methanol 21
2. (a) Alvarez, R.; Velazquez, S.; San-Felix, A.; Aquaro, S.; DeClercq, E.; Perno, C.-F.;
Karlsson, A.; Balzarini, J.; Carmarasa, M. J. J. Med. Chem. 1994, 37, 4185; (b)
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Garmon, S. A.; Graber, D. R.; Grega, K. C.; Hester, J. B.; Hutchinson, D. K.; Morris,
81% from 20; For 21: ½a D25
ꢁ
¼ ꢀ60:3 (c 1, CHCl3), 1H NMR
(200 MHz, CDCl3/D2O): d = 1.40 (s, 3H), 1.43 (s, 3H), 2.33 (br s,
1H, –OH) 3.30 (dd, J = 4.6 Hz, 1H), 3.54 (dd, J = 3.8 Hz, 1H),
3.58ꢀ3.82 (m, 2H), 3.90ꢀ4.11 (m, 2H). 13C NMR (75 MHz, CDCl3):