dried with Na2SO4, concentrated, then purified by flash chromatography (mobile phase: gradient
cyclohexane/EtOAc 100/0 to 0/100) on silica (40-60 µm) pre-packed column to afford pure
cyanoazaindolizinyl-indolizines 4a-d.
Methyl 3-(3-cyanoimidazo[1,2-a]pyridin-2-yl)-indolizine-1-carboxylate (4a). The general procedure C was
used with 1.0 g (6.47 mmol, 1.0 equiv.) of 1-(cyanomethyl)-pyridinium chloride 2a and methyl propiolate
(0.82 g, 0.86 mL, 9.70 mmol, 1.5 equiv.) to obtain pure azaindolizine-indolizine 4a. Brown solid; 0.56g (54%);
mp (EtOAc/cyclohexane) = 254-256 °C; Rf (EtOAc/cyclohexane 5/5) = 0.52. 1H NMR (CDCl3, 500 MHz) δ (ppm):
3.93 (s, 3H, CH3), 6.94 (t, J = 7.0 Hz, 1H, ArH), 7.10 (t, J = 7.0 Hz, 1H, ArH), 7.24 (d, J = 8.0 Hz, 1H, ArH), 7.47 (t,
J = 8.0 Hz, 1H, ArH), 7.73 (d, J = 8.5 Hz, 1H, ArH), 8.10 (s, 1H, ArH), 8.35 (m, 2H, ArH), 10.00 (d, J = 7.0 Hz, 1H,
ArH ). 13C NMR (CDCl3, 100 MHz) δ (ppm): 51.1 (CH3), 92.8 (C), 105.1 (C), 112.7 (C), 113.7 (CH), 114.8 (CH),
116.0 (C), 117.6 (CH), 118.8 (CH), 119.5 (CH), 124.4 (CH), 125.4 (CH), 127.7 (CH), 128.7 (CH), 137.8 (C), 146.5
(C), 146.7 (C), 164.8 (C). IR ν (cm-1): 2204, 2008, 1697, 1688, 1632, 1557, 1517, 1487, 1449, 1316, 1295, 1245,
1216, 1056, 777, 759, 741, 437, 425. Elem. Analysis calcd. for C18H12N4O2: C, 68.35; H, 3.82; N, 17.71. Found:
C, 68.46; H, 4.13; N, 18.09%.
Ethyl 3-(3-cyano-7-methylimidazo[1,2-a]pyridin-2-yl)-7-methylindolizine-1-carboxylate (4b). The general
procedure C was used with 1.0 g (5.93 mmol, 1.0 equiv.) of 1-(cyanomethyl)-4-methylpyridinium chloride 2b
and ethyl propiolate (0.87 g, 0.90 mL, 8.89 mmol, 1.5 equiv.) to obtain pure azaindolizine-indolizine 4b.
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Yellow solid; 0.66 g (62%); mp (EtOAc/cyclohexane) > 230 °C; Rf (EtOAc/cyclohexane 5/5) = 0.56. H NMR
(CDCl3, 500 MHz) δ (ppm): 1.34 (t, J = 7.0 Hz, 3H, CH3), 2.45 (s, 3H, CH3), 2.50 (s, 3H, CH3), 4.40 (q, J = 7.0 Hz,
2H, CH2), 6.77 (d, J = 7.0 Hz, 1H, ArH), 6.93 (d, J = 6.5 Hz, 1H, ArH), 7.51 (s, 1H, ArH), 8.05 (s, 1H, ArH), 8.15 (s,
1H, ArH), 8.23 (d, J = 6.5 Hz, 1H, ArH), 8.87 (d, J = 7.0 Hz, 1H, ArH). 13C NMR (CDCl3, 100 MHz) δ (ppm): 14.7
(CH3), 21.4 (CH3), 21.6 (CH3), 59.7 (CH2), 92.0 (C), 104.1 (C), 113.1 (C), 115.6 (C), 116.1 (CH), 116.3 (CH), 117.2
(CH), 118.1 (CH), 118.7 (CH), 124.6 (CH), 127.2 (CH), 135.4 (C), 138.3 (C), 140.3 (C), 146.9 (C), 147.0 (C), 164.7
(C). IR ν (cm-1): 2355, 2339, 2193, 1680, 1642, 1562, 1515, 1481, 1463, 1346, 1315, 1247, 1223, 1193, 1159,
1102, 1048, 875, 793, 776, 702, 667, 608, 523, 504, 459, 437. Elem. Analysis calcd. for C21H18N4O2: C, 70.38;
H, 5.06; N, 15.63. Found: C, 70.77; H, 5.20; N, 15.81%.
Methyl 3-(3-cyano-6,8-dimethylimidazo[1,2-a]pyridin-2-yl)-6,8-dimethylindolizine-1-carboxylate (4c). The
general procedure C was used with 1.0 g (5.47 mmol, 1.0 equiv.) of 1-(cyanomethyl)-3,5-dimethylpyridinium
chloride 2c and methyl propiolate (0.69 g, 0.73 mL, 8.21 mmol, 1.5 equiv.) to obtain pure azaindolizine-
indolizine 4c. Yellow solid; 0.46 g (45%); mp (CHCl3): 231-233 °C; Rf (EtOAc/cyclohexane 5/5) = 0.70. 1H NMR
(CDCl3, 500 MHz) δ (ppm): 2.34 (s, 3H, CH3), 2.39 (s, 3H, CH3), 2.67 (s, 3H, CH3), 2.79 (s, 3H, CH3), 3.88 (s, 3H,
CH3), 6.84 (s, 1H, ArH), 7.10 (s, 1H, ArH), 8.00 (s, 1H, ArH), 8.03 (s, 1H, ArH), 9.75 (s, 1H, ArH). 13C NMR (CDCl3,
100 MHz) δ (ppm): 16.8 (CH3), 18.3 (CH3), 18.6 (CH3), 22.1 (CH3), 51.5 (CH3), 93.3 (C), 106.4 (C), 113.4 (C),
115.6 (C), 120.3 (CH), 121.2 (CH), 122.9 (C), 123.4 (CH), 125.0 (C), 127.2 (C), 128.6 (CH), 129.3 (C), 130.7 (CH),
135.6 (C), 145.8 (C), 146.0 (C), 165.0 (C). IR ν (cm-1): 3091, 2941, 2920, 2209, 1707, 1556, 1492, 1446, 1359,
1333, 1282, 1263, 1202, 1060, 988, 943, 840, 771, 710, 582, 543, 487. Elem. Analysis calcd. for C22H20N4O2: C,
70.95; H, 5.41; N, 15.04. Found: C, 71.32; H, 5.70; N, 15.37%.
Ethyl 3-(3-cyano-6,8-dimethylimidazo[1,2-a]pyridin-2-yl)-6,8-dimethylindolizine-1-carboxylate (4d). The
general procedure C was used with 1.0 g (5.47 mmol, 1.0 equiv.) of 1-(cyanomethyl)-3,5-dimethylpyridinium
chloride 2c and ethyl propiolate (0.805 g, 0.832 mL, 8.21 mmol, 1.5 equiv.) to obtain pure azaindolizine-
indolizine 4d. White solid; 0.45 g (42%); mp (EtOAc/cyclohexane): 221-224 °C; Rf (EtOAc/cyclohexane 5/5) =
0.80; 1H NMR (CDCl3, 500 MHz) δ (ppm): 1.43 (t, J = 7.0 Hz, 3H, CH3), 2.34 (s, 3H, CH3), 2.36 (s, 3H, CH3), 2.64
(s, 3H, CH3), 2.77 (s, 3H, CH3), 4.35 (q, J = 7.0 Hz, 2H, CH2), 6.81 (s, 1H, ArH), 7.07 (s, 1H, ArH), 7.95 (s, 1H,
ArH), 8.01 (s, 1H, ArH), 9.73 (s, 1H, ArH). 13C NMR (CDCl3, 125 MHz) δ (ppm): 16.7 (CH3), 18.5 (CH3), 18.7
(CH3), 22.2 (CH3), 51.7 (CH3), 59.6 (CH2), 93.5 (C), 106.5 (C), 113.2 (C), 115.6 (C), 120.8 (CH), 121.1 (CH), 123.1
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