Synlett 2010(14): 2067-2070  
DOI: 10.1055/s-0030-1258532
LETTER
© Georg Thieme Verlag Stuttgart ˙ New York

Study of Reactivity in the 1,3-Dipolar Cycloaddition Reactions Leading to New Triazolopyrrolopyrazine Ring Systems

Antonino Lauria, Annalisa Guarcello, Gaetano Dattolo, Anna Maria Almerico
Dipartimento Farmacochimico, Tossicologico e Biologico, Università di Palermo, Via Archirafi 32, 90123 Palermo, Italy
e-Mail: lauria@unipa.it;
Further Information

Publication History

Received 1 May 2010
Publication Date:
28 July 2010 (online)

Abstract

The influence of the structural symmetry of the 2π double-reactive-sites component in the 1,3-dipolar cycloaddition reactions, involving nitrilimines as dipoles, was investigated. The experimental data showed that the loss of the symmetry leads to the formation of the monocycloadduct in good yields.

    References and Notes

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14

General Procedure for the 1,3-Dipolar Cycloaddition Reactions of 2-Phenyl[1 H ]pyrrolo[2,3- b ]pyrazine¹5 (12) and Chlorophenylhydrazones¹6,¹7 6′a-d (Method B)
Triethylamine (20.48 mmol) was added to a solution of
2-phenyl[1H]pyrrolo[2,3-b]pyrazine (12, 2.56 mmol,
0.5 g) and chlorophenylhydrazones 6′a-d (5.12 mmol) in anhydrous THF (20 mL). The mixture was stirred at r.t. for 96 h. In the case of the reaction of 12 and 6′a, methyl 3,7-diphenyl-5,6-dihydro-3H-pyrrolo[2,3-e][1,2,4]triazolo[4,3-a]pyrazine-1-carboxylate (14a) was directly filtered from the mixture; yield 60%; mp 188-189 ˚C, from EtOH. IR: 3430-3093 (NH), 1731 (C=O), 1556 (C=N) cm. ¹H NMR [200 MHz, (CD3)2 SO]: δ = 3.82 (s, 3 H, CH3), 6.82 (s, 1 H, H-8), 7.04 (t, 1 H, 4-NC6H5, J = 6.6 Hz), 7.25-7.46 (m, 6 H, ArH), 8.03-8.05 (m, 1 H, 4-C6H5), 8.21-8.25 (m, 3 H, ArH, H-4), 10.82 (s, N H). ¹³C NMR [50.3 MHz, (CD3)2 SO]: δ = 52.8 (q), 89.1 (d), 114.8 (d), 120.7 (s), 121.6 (s), 123.2 (d), 127.7 (d), 128.7 (d), 129.3 (d), 129.7 (d), 130.2 (d), 130.8 (s), 135.3 (s), 142.4 (s), 160.4 (s), 168.7 (s). Anal. Calcd for. C21H17N5O2: C, 67.91; H, 4.61; N, 18.86. Found: C, 67.96; H, 4.68; N, 18.92.
The solution was evaporated under reduced pressure, the residue was washed with EtOH (5 mL) and chromatog-raphed on a silica gel column using CH2Cl2 as the eluent. The first fraction eluted gave 3,9-dimethoxycarbonyl-1,6,11-triphenyl(1,11,11a,11b-tetrahydrobis-1,2,4-triazolo[3,4-c:4′,3′-a]-3H-pyrrolo[2,3-e]pyrazine) (13a); yellow solid, yield 13%; mp 214-215 ˚C, from EtOH. IR: 3407-3166 (NH), 1733, 1708 (C=O), 1594 (C=N) cm. ¹H NMR [200 MHz, (CD3)2 SO]: δ = 3.91 (s, 3 H, CH3), 3.96
(s, 3 H, CH3), 5.83 (d, 1 H, H-11a, J = 7.6 Hz), 5.95 (d, 1 H, H-11b, J = 7.6 Hz), 6.75-6.77 (m, 3 H, H-5, 4-NC6H5), 7.07-7.23 (m, 10 H, ArH), 7.35-7.43 (m, 2 H, 3-NC6H5), 7.55-7.59 (m, 2 H, 3-NC6H5), 10.77 (s, NH). ¹³C NMR [50.3 MHz, (CD3)2 SO]: δ = 52.8 (q), 53.0 (q), 73.3 (d), 74.6 (d), 97.5 (d), 110.0 (s), 113.1 (d), 113.2 (d), 115.0 (s), 120.8 (d), 120.9 (d), 123.2 (d), 124.9 (s), 125.9 (d), 128.8 (2 d), 128.9 (d), 132.2 (s), 140.6 (s), 142.8 (s), 143.4 (s), 144.2 (s), 158.4 (s), 158.6 (s). Anal. Calcd for C30H25N7O4: C, 65.80; H, 4.60; N, 17.91. Found C, 65.76; H, 4.65; N, 18.02.
The second fraction eluted with CH2Cl2-EtOAc (98:2)gave methyl 6-[methoxy-N-phenyl-2-oxoethanhydrazonyl]-3,7-diphenyl-5,6-dihydro-3H-pyrrolo[2,3-e][1,2,4]triazolo[4,3-a]pyrazine-1-carboxylate (16a); yellow solid, yield 6%; mp 218-219 ˚C, from EtOH. IR: 3358-3021 (NH), 1739 (C=O), 1596 (C=N) cm. ¹H NMR [200 MHz, (CD3)2 SO]: δ = 3.60 (s, 3 H, CH3), 3.95 (s, 3 H, CH3), 7.27 (s, 1 H, H-8), 7.37-7.56 (m, 11 H, ArH), 7.65 (d, 2 H, 2-C6H5, J = 7.0 Hz), 7.72 (d, 2 H, 2-C6H5, J = 7.8 Hz), 8.32 (d, 2 H, 3-C6H5, J = 7.8 Hz), 8.48 (s, 1 H, H-4). ¹³C NMR (50.3 MHz, CDCl3): δ = 52.8 (q), 52.9 (q), 108.3 (d), 110.9 (s), 120.0 (d), 120.9 (s)125.1 (d), 126.9 (d), 127.8 (d), 128.2 (d), 129.1 (d), 129.2 (d), 129.4 (d), 130.0 (d), 131.7 (s), 133.4 (d), 137.2 (s), 150.5 (s), 153.0 (s), 156.7 (s), 160.3 (s). Anal. Calcd for C30H25N7O4: C, 65.80; H, 4.60; N, 17.91. Found: C, 65.73; H, 4.57; N, 18.05.
Further fraction eluted with CH2Cl2-EtOAc (95:5), afforded methyl 3,7-diphenyl-3H-pyrrolo[2,3-e][1,2,4]triazolo[4,3-a]pyrazine-1-carboxylate (15a); very bright orange solid, yield 10%; mp 254-255 ˚C, from EtOH. IR: 1735 (C=O), 1552 (C=N) cm. ¹H NMR [200 MHz, (CD3)2 SO]: δ = 3.99 (s, 3 H, CH3), 7.51 (s, 1 H, H-8), 7.61-7.72 (m, 5 H, ArH), 7.75 (d, 2 H, 2-NC6H5, J = 6.6 Hz), 8.04 (d, 2 H, 3-C6H5, J = 7.3 Hz), 8.45-8.47 (m, 2 H, ArH, H-4). ¹³C NMR [50.3 MHz, (CD3)2 SO]: δ = 53.0 (q), 91.4 (d), 124.3 (2 d), 129.0 (2 d), 129.9 (d), 130.5 (d), 132.4 (d), 133.9 (s), 134.5 (s), 142.4 (s), 144.6 (s), 162.8 (s), 163.2 (s), 177.1 (s). Anal. Calcd for C21H15N5O2: C, 68.28; H, 4.09; N, 18.96. Found: C, 68.36; H, 4.16; N, 19.03. For the experimental details of all reactions see Supporting Information.