5706
G. Cai et al. / Tetrahedron 62 (2006) 5697–5708
62.5, 53.2, 50.6, 50.0, 42.5, 22.4, 21.0; ESI-MS 211.3
(M+H)+; HRMS calcd for C10H14N2O3Na 233.0897
(M+Na)+, found 233.0893.
(m, 9H), 0.88 (m, 3H); 13C NMR (75 MHz, CDCl3) d 168.4,
166.6, 148.3, 136.2, 128.7, 128.3, 127.7, 91.4, 58.3, 53.2,
50.5, 49.8, 47.3, 31.7, 31.0, 29.7, 25.4, 23.2, 18.3, 14.0;
EIMS m/z 370 (M)+.
4.4.7. 2-Benzyl-3-oxo-2,3,4,6,7,8-hexahydro-1H-pyrido-
[1,2-a]pyrazine-9-carboxylic acid methyl ester (17g). IR
4.4.12. (S)-2-Benzyl-6-(3,4-dimethoxyphenyl)-3-oxo-
2,3,4,6,7,8-hexahydro-1H-pyrido[1,2-a]pyrazine-9-car-
boxylic acid methyl ester (17l). [a]2D0 +33.4 (c 0.89, CHCl3);
(film) 3406, 2952, 1737, 1681, 1587 cmꢁ1 1H NMR
;
(300 MHz, CDCl3) d 7.34–7.27 (m, 5H), 4.73 (s, 2H), 4.64
(s, 2H), 3.81 (s, 2H), 3.60 (s, 3H), 3.16 (t, J¼5.4 Hz, 2H),
2.36 (t, J¼5.4 Hz, 2H), 1.85 (m, 2H); 13C NMR (75 MHz,
CDCl3) d 168.4, 165.8, 149.3, 136.0, 128.9, 128.7, 127.7,
92.4, 53.5, 50.6, 49.7, 47.6, 29.7, 22.3, 20.9; ESI-MS
301.2 (M+H)+; HRMS calcd for C17H20N2O3Na 323.1366
(M+Na)+, found 323.1360.
1
IR (film) 2924, 1674, 1642, 1562, 1278, 1124 cmꢁ1; H
NMR (300 MHz, CDCl3) d 7.35–7.26 (m, 5H), 6.80 (d,
J¼7.8 Hz, 1H), 6.65 (m, 2H), 4.91 (s, 2H), 4.74 (d, J¼
14.7 Hz, 1H), 4.58 (d, J¼14.7 Hz, 1H), 4.28 (t, J¼4.5 Hz,
1H), 3.87 (s, 3H), 3.82 (s, 3H), 3.83 (d, J¼13.8 Hz, 1H),
3.73 (d, J¼13.8 Hz, 1H), 3.62 (s, 3H), 2.47 (m, 1H), 2.11–
1.89 (m, 3H); 13C NMR (75 MHz, CDCl3) d 168.2, 166.5,
149.5, 149.4, 148.7, 136.2, 133.5, 128.8, 128.4, 127.8,
118.4, 111.5, 109.4, 92.8, 62.0, 56.0, 52.5, 50.7, 49.8, 47.1,
31.9, 29.7, 22.7; ESI-MS 437.25 (M+H)+; HRMS calcd for
C25H29N2O5 437.2071 (M+H)+, found 437.2063.
4.4.8. (R)-3-Oxo-6-pentyl-2,3,4,6,7,8-hexahydro-1H-pyr-
ido[1,2-a]pyrazine-9-carboxylic acid methyl ester (17h).
[a]2D0 ꢁ78.2 (c 0.25, CHCl3); IR (film) 2931, 2858, 1686,
1
1574 cmꢁ1; H NMR (300 MHz, CDCl3) d 5.96 (m, 1H),
4.85 (dd, J¼18.0, 3.6 Hz, 2H), 3.90 (d, J¼9.0 Hz, 1H),
3.76 (d, J¼9.0 Hz, 1H), 3.63 (s, 3H), 3.17 (m, 1H), 2.50
(m, 1H), 2.24 (m, 1H), 1.90 (m, 1H), 1.72–1.30 (m, 9H),
0.83 (m, 3H); 13C NMR (75 MHz, CDCl3) d 169.0, 168.6,
147.8, 91.8, 58.8, 53.0, 50.7, 42.2, 31.07, 31.0, 25.4, 23.2,
22.5, 18.4, 14.1; ESI-MS 281.25 (M+H)+; HRMS calcd for
C15H25N2O3 281.1860 (M+H)+, found 281.1864.
4.4.13. (R)-2-Benzyl-6-methyl-3-oxo-2,3,4,6,7,8-hexa-
hydro-1H-pyrido[1,2-a]pyrazine-9-carboxylic acid
methyl ester (17m). [a]2D0 ꢁ10.3 (c 1.2, CHCl3); IR (film)
3449, 1708, 1579, 1364 cmꢁ1
;
1H NMR (300 MHz,
CDCl3) d 7.36–7.27 (m, 5H), 4.90 (d, J¼17.7 Hz, 1H), 4.70–
4.57 (m, 3H), 3.94 (d, J¼16.8 Hz, 1H), 3.75 (d, J¼16.5 Hz,
1H), 3.61 (s, 3H), 3.38 (m, 1H), 2.49 (dt, J¼15.0, 4.2 Hz,
1H), 2.28 (m, 1H), 1.72 (m, 2H), 1.13 (d, J¼6.3 Hz, 3H);
13C NMR (75 MHz, CDCl3) d 168.4, 166.6, 148.3, 136.1,
128.7, 128.3, 127.7, 91.4, 53.3, 52.1, 50.6, 49.8, 47.3,
31.9, 29.4, 22.7; ESI-MS 315.20 (M+H)+; HRMS calcd for
C18H23N2O3 315.1703 (M+H)+, found 315.1701.
4.4.9. (S)-6-(3,4-Dimethoxyphenyl)-3-oxo-2,3,4,6,7,8-
hexahydro-1H-pyrido[1,2-a]pyrazine-9-carboxylic acid
methyl ester (17i). [a]D20 +30.7 (c 0.47, CHCl3); IR (film)
1
3302, 2952, 1868, 1517, 1272 cmꢁ1; H NMR (300 MHz,
CDCl3) d 6.82 (d, J¼8.1 Hz, 1H), 6.69–6.63 (m, 2H), 6.38
(m, 1H), 4.95 (m, 2H), 4.30 (m, 1H), 3.87 (s, 3H), 3.85 (s,
3H), 3.79 (d, J¼16.5 Hz, 1H), 3.68 (d, J¼16.5 Hz, 1H),
3.66 (s, 3H), 2.50 (m, 1H), 2.18–1.91 (m, 2H), 1.70 (m,
1H); 13C NMR (75 MHz, CDCl3) d 168.9, 168.4, 149.5,
148.9, 148.7, 133.4, 118.4, 111.5, 109.4, 93.1, 62.3, 56.0,
52.2, 50.8, 42.0, 29.7, 28.8, 18.7; ESI-MS 347.20 (M+H)+;
HRMS calcd for C18H23N2O5 347.1602 (M+H)+, found
347.1608.
4.4.14. (6R,7S)-7-Ethyl-3-oxo-6-propyl-2,3,4,6,7,8-hexa-
hydro-1H-pyrido[1,2-a]pyrazine-9-carboxylic acid
methyl ester (17n). [a]D20 ꢁ30.8 (c 0.46, CHCl3); IR (film)
2961, 2931, 1692 cmꢁ1 1H NMR (300 MHz, CDCl3)
;
d 5.89 (m, 1H), 4.82 (m, 2H), 3.93–3.75 (m, 3H), 3.64 (s,
3H), 2.92 (m, 1H), 2.40–2.30 (m, 2H), 1.66 (m, 1H), 1.47–
1.13 (m, 5H), 0.99–0.83 (m, 6H); 13C NMR (75 MHz,
CDCl3) d 169.1, 168.8, 146.9, 89.6, 63.0, 53.8, 50.7, 42.0,
34.7, 34.1, 31.9, 29.4, 22.7, 19.2, 14.1; ESI-MS 281.25
(M+H)+; HRMS calcd for C15H25N2O3 281.1860 (M+H)+,
found 281.1866.
4.4.10. (R)-6-Methyl-3-oxo-2,3,4,6,7,8-hexahydro-1H-
pyrido[1,2-a]pyrazine-9-carboxylic acid methyl ester
(17j). [a]2D0 +27.7 (c 0.89, CHCl3); IR (film) 2954, 2850,
1
1686, 1274 cmꢁ1; H NMR (300 MHz, CDCl3) d 5.92 (m,
1H), 4.98 (dd, J¼18.0, 3.6 Hz, 1H), 4.66 (d, J¼16.8 Hz,
1H), 3.90 (d, J¼16.5 Hz, 1H), 3.70 (d, J¼16.5 Hz, 1H),
3.66 (s, 3H), 3.38 (m, 1H), 2.55 (m, 1H), 2.29 (m, 1H),
2.05 (m, 1H), 1.83–1.72 (m, 1H), 1.14 (d, J¼6.3 Hz, 3H);
13C NMR (75 MHz, CDCl3) d 169.0, 168.6, 147.9, 92.0,
53.7, 51.9, 50.7, 42.2, 31.9, 26.4, 18.2; ESI-MS 225.15
(M+H)+; HRMS calcd for C11H17N2O3 225.1234 (M+H)+,
found 225.1242.
4.4.15. (6R,7S)-2-Benzyl-7-ethyl-3-oxo-6-propyl-2,3,4,
6,7,8-hexahydro-1H-pyrido[1,2-a]pyrazine-9-carboxylic
acid methyl ester (17o). [a]2D0 ꢁ36.8 (c 0.69, CHCl3); IR
(film) 2958, 1684, 1579, 1458, 1268 cmꢁ1 1H NMR
;
(300 MHz, CDCl3) d 7.38–7.27 (m, 5H), 4.76 (s, 2H), 4.63
(m, 2H), 3.96 (d, J¼16.8 Hz, 1H), 3.83 (d, J¼16.5 Hz,
1H), 3.60 (s, 3H), 2.93 (m, 1H), 2.27 (m, 2H), 1.70–1.11
(m, 7H), 0.95–0.86 (m, 6H); 13C NMR (75 MHz, CDCl3)
d 168.9, 166.6, 147.4, 136.2, 128.7, 128.2, 127.7, 89.2,
62.7, 54.2, 50.6, 49.7, 47.0, 35.0, 34.1, 31.9, 29.4, 25.3,
22.7, 14.1; ESI-MS 371.25 (M+H)+; HRMS calcd for
C22H31N2O3 371.2329 (M+H)+, found 371.2329.
4.4.11. (R)-2-Benzyl-3-oxo-6-pentyl-2,3,4,6,7,8-hexa-
hydro-1H-pyrido[1,2-a]pyrazine-9-carboxylic acid
methyl ester (17k). [a]D20 ꢁ43.0 (c 0.62, CHCl3); IR (film)
1
2956, 2931, 2858, 1739, 1686 cmꢁ1; H NMR (300 MHz,
CDCl3) d 7.38–7.28 (m, 5H), 4.81 (d, J¼17.7 Hz, 1H),
4.72 (d, J¼17.7 Hz, 1H), 4.67 (d, J¼14.4 Hz, 1H), 4.58
(d, J¼14.4 Hz, 1H), 3.94 (d, J¼15.9 Hz, 1H), 3.81
(d, J¼16.5 Hz, 1H), 3.60 (s, 3H), 3.16 (m, 1H), 2.47 (dd,
J¼16.8, 4.5 Hz, 1H), 2.16 (m, 1H), 1.86 (m, 1H), 1.68–1.29
4.4.16. (S)-2-((tert-Butoxycarbonyl)methyl)-6-(3,4-di-
methoxyphenyl)-1-(2-methoxy-2-oxoethyl)-1,4,5,6-tetra-
hydropyridine-3-carboxylic acid methyl ester (18a). To a
solution of 17i (20 mg, 0.058 mmol) in methylene chloride
were added triethylamine (8 mL, 0.058 mmol), di-tert-butyl