2026
M. TUKULULA, R. KLEIN, AND P. T. KAYE
(C¼O); dH (400 MHz; CDCl3) 3.80 (3H, s, CH3), 4.27 (2H, d, J 5.2 Hz, CH2), 6.71
(1H, d, J 0.8 Hz, Ar-H), 6.75 (1H, br s, NH), 6.98 (1H, d, J 9.2 Hz, Ar-H), 7.20
(1H, d, J 9.6 Hz, Ar-H), 7.33 (1H, t, J 7.6 Hz, Ar-H), 7.48 (1H, t, J 7.6 Hz, Ar-H),
7.59 (1H, d, J 7.6 Hz, Ar-H), 7.82 (1H, d, J 8.4 Hz, Ar-H) and 8.33 (1H, s, Ar-H);
dC (100 MHz; CDCl3) 41.3 (t), 52.3 (q), 100.7 (d), 114.2 (d), 114.4 (d), 118.7 (d),
120.4 (d), 122.0 (s), 124.0 (s), 124.6 (d), 128.2 (d), 128.7 (d), 131.3 (s), 132.9 (s),
164.7 (s) and 170.9 (s).
Methyl (2S)-1-[(5-Methylindolizin-2-yl)carbonyl]pyrrolidine-2-
carboxylate 24
Following the procedure described for the synthesis of N-[2-(benzylthio)-
ethyl]indolizine-2-carboxamide 20a, L-proline methyl ester hydrochloride 17
(0.200 g, 1.20 mmol) was reacted with 5-methylindolizine-2-carboxylic acid 8b
(0.100 g, 0.571 mmol) to afford methyl (2S)-1-[(5-methylindolizin-2-yl)carbonyl]-
pyrrolidine-2-carboxylate 24 as a brown oil (0.080 g, 50%). Found M þ 1:
287.1383; C16H19N2O3 requires MHþ, 287.1396. nmax(KBr)=cmꢃ1 1603 (NC¼O)
and 1736 (C¼O); dH (400 MHz; CDCl3) 2.00 (2H, m, CH2CH2CH2), 2.13 and
2.30 (2H, 2 ꢂ m, CHCH2), 2.48 (3H, s, Ar-CH3), 3.75 (3H, s, OCH3), 3.96 (2H, m,
NCH2), 4.69 (1H, dd, J 8.2 and 5.0 Hz, CHCH2), 6.40 (1H, d, J 6.8 Hz, Ar-H),
6.68 (1H, m, Ar-H), 6.78 (1H, s, Ar-H), 7.29 (1H, t, J 9.0 Hz, Ar-H) and 7.68
(1H, s, Ar-H); dC (100 MHz; CDCl3) 18.5 (q), 25.4 (t), 28.9 (t), 49.1 (t), 52.1 (q),
59.8 (d), 99.7 (d), 110.9 (d), 112.7 (d), 117.5 (d), 118.3 (d), 122.8 (s), 132.9 (s),
165.2 (s) and 173.0 (s).
1-(Indolizin-2-yl)-7-carbomethoxy-1,9,12-trioxo-2,8,11-
triazatridecane 25
Indolizine-2-carboxylic acid 8a (0.100 g, 0.63 mmol) in dry DMF (5 ml) was
reacted with N-acetyl-glycine-lysine methyl ester acetate salt 18 (0.150 g, 0.578 mmol)
following the procedure described for the preparation of N-[4-(diethylamino)-1-
methylbutyl]indolizine-2-carboxamide 19. The crude product was purified using pre-
parative layer chromatography [on silica; elution with CH2Cl2–methanol (20:4)] to
afford 1-(indolizine-2-yl)-7-carbomethoxy-1,9,12-trioxo-2,8,11-triazatridecane 25 as
a brown solid (0.150 g, 60.1%), mp 114–116 ꢀC. Found Mþ: 402.1880; C20H26N4O5
requires M, 402.1903.
n
max(nujol)=cmꢃ1 1741 (C¼O), 1664, 1638, 1630
(3 ꢂ NHC¼O); dH (400 MHz; CDCl3) 1.40 and 1.56 (4H, 2 ꢂ m, NCH2CH2CH2),
1.76 and 1.88 (2H, 2 ꢂ m, CH2CH), 1.99 (3H, s, CH3CO), 3.36 and 3.50 (2H,
2 ꢂ m, NCH2), 3.70 (3H, s, OCH3), 3.94 (1H, dd, J 16.8 and 4.8 Hz, NCHaCO)
and 4.05 (1H, dd, J 16.8 and 5.6 Hz, NCHbCO), 4.47 (1H, m, CH2CH), 6.50 (1H,
t, J 6.8 Hz, Ar-H), 6.16 (1H, br s, NH), 6.64–6.69 (2H, overlapping signals,
Ar-H), 6.89 (1H, m, NH), 7.30 (1H, d, J 8.8 Hz, Ar-H), 7.41 (1H, d, J 7.2 Hz,
NH), 7.85 (1H, s, Ar-H) and 7.90 (1H, d, J 6.8 Hz, Ar-H); dC (100 MHz; CDCl3)
22.0 (t), 22.9 (q), 29.1 (t), 30.8 (t), 38.3 (t), 43.1 (t), 52.2 (q), 52.4 (d), 97.1 (d),
111.9 (d), 114.3 (d), 118.4 (d), 119.7 (d), 123.3 (s), 125.6 (d), 132.9 (s), 165.6 (s),
169.2 (s), 170.8 (s) and 172.5 (s).