K. Gu et al. / Bioorg. Med. Chem. 14 (2006) 1339–1347
1345
Compound 5b: mp 114–116 ꢁC. FAB-MS m/z (%): 302
[M+H]+. 1H NMR (CDCl3, d): 1.22 (d, J = 5.8 Hz,
3H), 1.88 (m, J = 6.0 Hz, 2H), 3.24 (s, 6H), 3.76 (m,
J = 2.6 Hz, 1H), 4.01 (d, J = 2.6 Hz, 2H), 4.18 (t,
J = 6.0 Hz, 1H), 4.58 (m, J = 5.8 Hz, 1H), 4.69 (t,
J = 5.6 Hz, 1H), 8.03 (s, 1H). 13C NMR (CDCl3,d):
FAB-MS m/z (%): 310 [M+H]+. IR (KBr, cmꢂ1) m:
3441, 3052, 2970, 2933, 2866, 1655, 1601, 1571, 1480,
1410, 1376, 1360, 1175, 1065, 710, 692 cmꢂ1.1H NMR
(CDCl3, d): 1.21 (d, J = 6.2 Hz, 3H), 1.88 (m,
J = 6.2 Hz, 2H), 3.24 (s, 3H), 3.25 (s, 3H), 3.78 (m,
J = 2.5 Hz, 1H), 4.01 (m, J = 2.4 Hz, 2H), 4.18 (t,
J = 6.2 Hz, 1H), 4.58 (m, J = 2.7 Hz, 1H), 4.68 (t,
J = 5.5 Hz, 1H), 7.44 (t, J = 9.3 Hz, 2H), 7.52 (t,
J = 11.1 Hz, 1H), 7.83 (d, J = 11.1 Hz, 2H), 8.00(s,
1H). In a NOESY experiment an NOE between the
15.69, 41.94, 48.10, 56.18, 69.77, 71.70, 91.38, 96.39,
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125.55, 170.58. ½aꢁ ꢂ7.8 (c 2.0, CHCl3). Anal. calcd
for C11H18F3NO5: C, 43.86; H, 6.02; N, 4.65. Found:
C, 43.68; H, 6.20; N, 4.50.
CH3 at the 4-position and the CH2 at the 2-position
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Compound 7b: mp 103–105 ꢁC. FAB-MS m/z (%): 439
[M+H]+. 1H NMR (CDCl3, d): 1.21 (d, J = 6.3 Hz,
6H), 1.89 (t, J = 5.2 Hz, 2H), 3.77 (m, J = 1.8 Hz, 2H),
4.00 (d, J = 3.0 Hz, 4H), 4.60 (m, J = 6.0 Hz, 2H), 4.69
(t, J = 5.2 Hz, 2H), 8.02 (s, 2H). 13C NMR (CDCl3, d):
was observed. ½aꢁ ꢂ6.0 (c 2.0, CHCl3). Anal. calcd
for C16H23NO5: C, 62.12; H, 7.49; N, 4.53. Found: C,
62.01; H, 7.37; N, 4.64.
4.14. N,N0-Methylenebis[(2S,4R,5R)/(2R,4S,5S)-4-meth-
yl-1,3-dioxan-2,5-diyl]bisbenzoylamine (10b)
15.72, 42.49, 56.19, 69.77, 71.68, 91.33, 125.60, 171.00.
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½aꢁ ꢂ40.1 (c 2.0, MeOH). Anal. calcd for
C15H20F6N2O6: C, 41.10; H, 4.60; N, 6.39. Found: C,
41.30; H, 4.42; N, 6.25.
Using the same procedure as that for the preparation of
7a, starting from 120 mg (0.48 mmol) of 8b, 170 mg
(76%) of the title compound was obtained as a colorless
powder. Mp 134–137 ꢁC. FAB-MS m/z (%): 247
[M+H]+. 1H NMR (CDCl3, d): 1.19 (d, J = 6.4 Hz,
6H), 1.92 (t, J = 5.6 Hz, 2H), 3.66 (d, J = 1.8 Hz, 2H),
4.00 (d, J = 3.8 Hz, 4H), 4.53 (m, J = 1.8 Hz, 2H),
4.67(t, J = 1.9 Hz, 2H), 7.44 (t, J = 9.1 Hz, 4H), 7.52
(t, J = 10.8 Hz, 2H), 7.83 (d, J = 10.8 Hz, 2H), 7.89 (s,
1H). In a NOESY experiment, NOEs between the
CH3 at the 4-position and the CH2 at the 2-position,
4.12. (2S,4R,5R)-2-(2,2-Dimethoxylethyl)-4-methyl-1,3-di-
oxan-5-yl-amine (6b) and N,N0-methylenebis[(2S,4R,5R)/
(2R,4S,5S)-4-methyl-1,3-dioxan-2,5-diyl]bisamine (8b)
(A) Using the same procedure as that for the prepara-
tion of 6a, starting from 903 mg (3.0 mmol) of 5b,
572 mg (93%) of 6b was obtained as a colorless oil.
(B) Using the same procedure as that for the prepara-
tion of 6a, starting from 439 mg (1.0 mmol) of 7b,
221 mg (90%) of 8b was obtained as a colorless oil.
(C) Using the same procedure as that for the prepara-
tion of 6a, starting from 315 mg (3.0 mmol) of 3b,
480 mg (78%) of 6b and 80 mg (8%) of 8b was
obtained as a colorless oil.
and between the CH3 at the 4-position and the NH at
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the 5-position were observed. ½aꢁ ꢂ35.1 (c 2.0, MeOH).
Anal. calcd for C25H30N2O6: C, 66.06; H, 6.65; N, 6.16.
Found: C, 66.19; H, 6.71; N, 6.25.
4.15. N-[(2S,5S)-2-(2,2-Dimethoxyethyl)-1,3-dioxacyclo-
heptan-5-yl]trifluoroacetylamine (5c) and N-[(2R,5S)-2-
(2,2-dimethoxyethyl)-1,3-dioxacycloheptan-5-yl]trifluoro-
acetylamine (6c)
Compound 6b: FAB-MS m/z (%): 206 [M+H]+. 1H NMR
(CDCl3, d): 1.22 (d, J = 6.1 Hz, 3H), 1.87 (s, 2H), 1.89 (m,
J = 6.0 Hz, 2H), 2.77 (m, J = 1.9 Hz, 1H), 3.25 (s, 3H),
3.25 (s, 3H), 4.00 (m, J = 2.2 Hz, 2H), 4.188 (t,
J = 6.0 Hz, 1H), 4.21 (m, J = 2.5 Hz, 1H), 4.69 (t,
Using the same procedure as that for the preparation of
5a, starting from 603 mg (3.0 mmol) of 4c, 82 mg (13%)
of 5c and 83 mg (13%) of 6c were obtained as a colorless
powder.
J = 5.6 Hz, 1H). 13C NMR (CDCl3, d): 18.68, 45.91,
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48.11, 59.11, 76.39, 76.50, 93.35, 95.96. ½aꢁ ꢂ6.0 (c 2.0,
CHCl3). Anal. calcd for C9H19NO4: C, 52.67; H, 9.33;
N, 6.82. Found: C, 52.81; H, 9.50; N, 8.66.
Compound 5c: mp 120–122 ꢁC. FAB-MS m/z (%): 302
[M+H]+. 1H NMR (CDCl3, d): 1.46 (m, J = 5.0 Hz,
2H), 1.67 (t, J = 5.0 Hz, 2H), 1.90 (t, J = 4.8 Hz, 2H),
3.23 (s, 6H), 3.37 (t, J = 4.5 Hz, 2H), 4.18 (t,
J = 5.0 Hz, 1H), 4.18 (t, J = 4.5 Hz, 1H), 4.91 (t,
J = 5.1 Hz, 1H), 8.00 (s, 1H). In a NOE experiment, a
positive NOE between the NH at the 5-position and
the CH2 at the 2-position was observed. 13C NMR
Compound 8b: FAB-MS m/z (%): 247 [M+H]+. 1H
NMR (CDCl3, d): 1.19 (d, J = 6.5 Hz, 6H), 1.72 (s,
4H), 1.95 (t, J = 5.5 Hz, 2H), 2.45 (d, J = 1.5 Hz, 2H),
3.85 (m, J = 3.2 Hz, 4H), 3.95 (d, J = 1.5 Hz, 1H), 3.97
(d, J = 1.5 Hz, 1H), 4.72 (t, J = 5.5 Hz, 2H). 13C NMR
(CDCl3, d): 17.61, 50.48, 58.94, 73.48, 75.15, 95.04.
(CDCl3, d): 22.00, 33.16, 41.90, 48.10, 48.20, 63.80,
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½aꢁ ꢂ43.0 (c 2.0, MeOH). Anal. calcd for
71.38, 86.27, 96.37, 125.59, 170.60. ½aꢁ ꢂ33.4 (c 1.0,
C11H22N2O4: C, 53.64; H, 9.00; N, 11.37. Found: C,
53.79; H, 9.17; N, 11.25.
CHCl3). Anal. calcd for C11H18F3NO5: C, 43.86; H,
6.02; N, 4.65. Found: C, 43.69; H, 5.90; N, 4.79.
4.13. N-[(2S,4R,5R)-2-(20,20-Dimethoxyethyl)-4-methyl-
1,3-dioxan-5-yl]benzoylamine (9b)
Compound 6c: mp 107–109 ꢁC. FAB-MS m/z (%): 302
[M+H]+. 1H NMR (CDCl3, d): 1.46 (m, J = 4.2 Hz,
2H), 1.65 (q, J = 4.0 Hz, 2H), 1.88 (t, J = 4.6 Hz, 2H),
3.25 (s, 6H), 3.36 (t, J = 4.2 Hz, 2H), 4.20 (d,
J = 5.0 Hz, 1H), 4.23 (d, J = 4.9 Hz, 1H), 4.95 (t,
J = 4.0 Hz, 1H), 8.00 (s, 1H). In a NOESY experiment,
Using the same procedure as that for the preparation of
7a, starting from 98 mg (0.48 mmol) of 6b, 141 mg (95%)
of the title compound was obtained as a colorless oil.