G. M. Almiento et al. / Tetrahedron: Asymmetry 18 (2007) 2695–2711
2707
J = 7); 1.05 (d, 6H, J = 7); 1.27 (m 4H); 1.53 (s, 3H); 1.8–
2.1 (m, 2H); 2.1–2.42 (m, 3H); 2.57 (d, 1H, J = 14.2); 2.97
(d, 1H, J = 14.2); 3.33 (m, 1H); 3.57 (m, 1H); 3.69 (dd, 1H,
J = 1.8, 4); 3.83 (d, 1H, J = 3); 3.96 (d, 1H, J = 15); 4.16
(m, 6H); 5.32 (d, 1H, J = 15); 5.44 (d, 1H, J = 15); 6.9
(m, 1H); 7.2 (m, 10ArH). 13C NMR: d 13.9, 14.0, 17.2,
17.6, 19.9, 20.4, 28.4, 29.6, 31.5, 32.6, 37.1, 47.2, 47.6,
48.6, 57.1, 59.0, 60.9, 61.4, 61.6, 62.0, 127.3, 127.6, 128.0,
128.5, 128.7, 136.0, 136.1, 156.8, 159.8, 169.6, 170.0,
171.8. [a]D = +28.4 (c 0.9, CHCl3). Anal. Calcd for
C37H51N5O5: C, 68.81; H, 7.96; N, 10.84. Found: C,
68.95; H, 7.94; N, 10.82.
2.18 (m, 2H); 2.77 (qAB, 2H, J = 14.4); 3.10 (m, 2H);
3.71 (m, 1H); 3.80 (m, 1H); 3.85–4.15 (m, 6H); 5.26 (d,
1H, J = 15); 5.43 (d, 1H, J = 15); 6.42 (m, 1H); 7.18–
7.35 (m, 10ArH). 13C NMR: d 13.8, 14.0, 17.2, 20.3,
20.4, 24.3, 28.1, 28.7, 29.6, 29.7, 38.9, 40.4, 46.5, 47.2,
48.5, 59.1, 60.1, 60.6, 60.9, 61.1, 61.5, 127.5, 127.9, 128.2,
128.5, 128.6, 135.9, 156.0, 156.8, 170.0, 171.6, 172.1.
[a]D = +9.7 (c 1.2, CHCl3). Anal. Calcd for C39H55N5O5:
C, 69.51; H, 8.23; N, 10.39. Found: C, 69.66; H, 8.24; N,
10.4.
6.22. 2-[(2R,5S)-6-Ethoxy-2,3,4,5-tetrahydro-5-isopropyl-2-
methyl-3-oxopyrazin-2-yl]-N-[2-((2R,5S)-6-ethoxy-2,3,4,5-
tetrahydro-5-isopropyl-3-oxopyrazin-2-yl)ethyl]acetamide
18a
6.19. 2-[(2R,5S)-4-Benzyl-6-ethoxy-2,3,4,5-tetrahydro-5-
isopropyl-2-methyl-3-oxopyrazin-2-yl]-N-[2-((2R,5S)-4-
benzyl-6-ethoxy-2,3,4,5-tetrahydro-5-isopropyl-2-methyl-
3-oxopyrazin-2-yl)ethyl]acetamide 16b
A solution of 16a (6.45 g, 10 mmol) in 20 mL of dry THF/
t-butanol 9:1 was added to about 100 mL of liquid ammo-
nia cooled at ꢀ50 °C. Then, Li (0.14 g, 20 mmol) was
added. The addition of Li was stopped as soon as the reac-
tion mixture became blue, the starting material having dis-
appeared. The reaction was then quenched with NH4Cl
and the cooling bath removed to allow the complete evap-
oration of NH3. After addition of water and ethyl acetate,
the aqueous solution was acidified to pH 4 with diluted
HCl and the organic solution evaporated to dryness under
vacuum. The product was recovered as a wax in 94% yield.
1H NMR: d 0.86 (d, 6H, J = 7); 0.98 (d, 6H, J = 7); 1.27
(m, 6H); 1.41 (s, 3H); 1.90 (m, 1H); 2.20 (m, 3H), 2.47
(d, 1H, J = 14.4); 2.80 (d, 1H, J = 14.4); 3.40 (m, 2H);
3.86 (d, 1H, J = 2.6); 3.97–4.23 (m, 5H); 6.78 (br s, 1H);
6.84 (br s, 1H); 7.04 (br s, 1H). 13C NMR: d 14.0, 14.1,
16.3, 16.5, 18.3, 18.4, 28.1, 31.0, 32.3, 32.7, 36.5, 47.3,
56.6, 58.5, 58.6, 61.2, 61.4, 157.3, 159.4, 170.0, 172.1,
174.0. [a]D = +9.2 (c 0.2, CHCl3). Anal. Calcd for
C23H39N5O5: C, 59.33; H, 8.44; N, 15.04. Found: C,
59.43; H, 8.46; N, 15.1.
The compound was obtained starting from 14b following
the procedure described for 16a. 1H NMR: d 0.90 (d,
6H, J = 7); 1.05 (d, 3H, J = 7); 1.06 (d, 3H, J = 7); 1.25
(m, 6H); 1.48 (s, 3H); 1.52 (s, 3H); 1.90 (m, 1H); 2.18
(m, 3H); 2.59 (d, 1H, J = 14.2); 2.89 (d, 1H, J = 14.2);
3.08 (m, 1H); 3.30 (m, 1H); 3.76 (d, 1H; J = 2.8); 3.80
(d, 1H, J = 2,8); 4.10 (m, 6H); 5.35 (d, 2H, J = 15); 6.59
(m, 1H); 7.23 (m, 10 ArH). 13C NMR: d 13.7, 13.8, 17.1,
17.2, 20.2, 28.1, 28.2, 29.4, 29.6, 35.3, 41.5, 46.8, 48.3,
58.8, 56.0, 60.7, 61.3, 127.1, 127.3, 127.7, 127.8, 128.3,
128.5, 135.7, 135.8, 156.3, 156.6, 169.3, 171.5, 171.8.
[a]D = +7.1 (c 0.7, CH3OH). Anal. Calcd for C38H35-
N5O5: C, 69.17; H, 8.10; N, 10.61. Found: C, 69.42; H,
8.1; N, 10.57.
6.20. 2-[(2R,5S)-4-Benzyl-6-ethoxy-2,3,4,5-tetrahydro-5-
isopropyl-2-methyl-3-oxopyrazin-2-yl]-N-[2-((2R,5S)-4-
benzyl-6-ethoxy-2,3,4,5-tetrahydro-5-isopropyl-3-oxo-
pyrazin-2-yl)propyl]acetamide 17a
The compound was obtained starting from 15a and follow-
ing the procedure described for 16a. H NMR: d 0.92 (m,
6.23. 2-[(2R,5S)-6-Ethoxy-2,3,4,5-tetrahydro-5-isopropyl-2-
methyl-3-oxopyrazin-2-yl]-N-[2-((2R,5S)-6-ethoxy-2,3,4,5-
tetrahydro-5-isopropyl-2-methyl-3-oxopyrazin-2-yl)ethyl]-
acetamide 18b
1
6H); 1.05 (m, 6H); 1.21 (t, 3H, J = 7.2); 1.23 (t, 3H,
J = 7.2); 1.58 (s, 3H); 1.60 (m, 1H); 1.8–2.4 (m, 5H); 2.68
(d, 1H, J = 14.4); 2.95 (d, 1H, J = 14.4); 3.25 (m, 2H);
3.68 (m, 1H); 3.82 (d, 1H, J = 2.6); 3.91 (d, 1H,
J = 15.4); 4.1 (m, 5H); 5.34 (d, 1H, J = 15.4); 5.47 (d,
1H, J = 15.4); 6.58 (m, 1H); 7.3 (m, 10ArH). 13C NMR:
d 13.8, 13.9, 17.1, 17.4, 19.8, 20.3, 25.0, 28.0, 29.6, 30.6,
31.4, 38.9, 47.2, 48.4, 57.2, 59.0, 60.9, 61.0, 61.5, 61.8,
127.3, 127.4, 127.6, 127.9, 128.4, 128.5, 135.9, 136.0,
156.7, 159.3, 169.7, 170.1, 171.6. [a]D = +31.2 (c 2.2,
CHCl3). Anal. Calcd for C38H53N5O5: C, 69.17; H, 8.10;
N, 10.61. Found: C, 69.5; H, 8.08; N, 10.6.
The compound was obtained starting from 16b following
1
the procedure described for 18a H NMR: d 0.87 (t, 6H,
J = 7); 0.99 (d, 3H, J = 7); 1.01 (d, 3H, J = 7); 1.78 (m,
1H); 2.20 (m, 3H); 2.59 (qAB, 2H, J = 14.8); 3.10 (m,
1H); 3.38 (m, 1H); 3.90 (m, 2H); 4.15 (m, 4H); 6.60 (m,
1H) 7.17 (br s, 1H); 7.23 (br s, 1H). 13C NMR: d 14.1,
14.2, 16.3, 16.8, 18.4, 18.6, 27.4, 29.2, 30.9, 31.4, 35.0,
40.4, 46.8, 58.2, 58.4, 58.6, 61.1, 61.3, 157.4, 157.5, 169.8,
173.8, 174.7. [a]D = +12.0 (c 0.9, CHCl3). Anal. Calcd for
C24H41N5O5: C, 60.10; H, 8.62; N, 14.60. Found: C,
60.32; H, 8.64; N, 14.57.
6.21. 2-[(2R,5S)-4-benzyl-6-ethoxy-2,3,4,5-tetrahydro-5-iso-
propyl-2-methyl-3-oxopyrazin-2-yl]-N-[2-((2R,5S)-4-benzyl-
6-ethoxy-2,3,4,5-tetrahydro-5-isopropyl-2-methyl-3-oxopyr-
azin-2-yl)propyl]acetamide 17b
6.24. 2-[(2R,5S)-6-Ethoxy-2,3,4,5-tetrahydro-5-isopropyl-2-
methyl-3-oxopyrazin-2-yl]-N-[2-((2R,5S)-6-ethoxy-2,3,4,5-
tetrahydro-5-isopropyl-3-oxopyrazin-2-yl)propyl]acetamide
19a
The compound was obtained starting from 15b following
the procedure described for 16a. 1H NMR: d 0.87 (d,
6H, J = 7); 1.03 (d, 6H, J = 7); 1.20 (m, 6H); 1.42 (s,
3H); 1.52 (s, 3H); 1.10–1.60 (m, 3H); 1.98–2.24 (m, 1H);
The compound was obtained starting from 17a following
the procedure described for 18a. 1H NMR: d 0.92 (m,