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K. Kuchkova et al.
LETTER
(3 H, s, H-15), 0.76 (3 H, s, H-16). 13C NMR (100 MHz,
CDCl3): δ = 172.64 (s, C-12), 158.32 (d, C-20), 158.32 (d,
C-18), 157.70 (s, C-17), 149.27 (s, C-8), 116.14 (d, C-19),
106.51 (t, C-13), 55.21 (d, C-5), 52.27 (d, C-9), 42.12 (t, C-
3), 39.24 (s, C-10), 39.09 (t, C-1), 37.67 (t, C-7), 33.57 (q,
C-14), 33.56 (t, C-11), 33.53 (s, C-4), 24.13 (t, C-6), 21.77
(q, C-15), 19.35 (t, C-2), 14.75 (q, C-16).
chromatography on silica (CHCl3). The following
supplementary operations and remarks were to be pointed
out in the case of reaction products derived from amine 6c:
elution with CHCl3 afforded gradually the bisacylamide 8,
the monoacyl amide 7c, and a two-component mixture. This
mixture was subject to a second flash over silica (PE–Et2O,
8:2) when monoacyl amide 7c and some unreacted acid 4
were separated.
(32) 2-Bis-Δ8,13-bicyclohomofarnezenoylaminopyrimidine (8)
White crystals; mp 205–206 °C. [α]D26 27.78 (c 0.33,
CHCl3). IR: 3088, 897 (semicyclic methylene), 1704 (C=O,
amide), 1644, 1567, 1460, 1410, 1162 (pyrimidine cycle)
cm–1. 1H NMR (400 MHz, CDCl3): δ = 8.87 (2 H, d, J = 4.9
Hz, H-18, H-20), 7.34 (1 H, t, J = 4.9 Hz, H-19), 4.80 (2 H,
s, Ha-13, Ha-13′), 4.52 (2 H, s, Hb-13, Hb-13′), 2.72 (2 H,
dd, J = 16.9, 2.6 Hz, Ha-11, Ha-11′), 2.56 (2 H, dd, 16.9,
10.2 Hz, Hb-11, Hb-11′), 2.49 (2 H, dd, J = 10.0, 2.0 Hz, H-
9, H-9′), 2.39 (2 H, ddd, J = 13.0, 4.0, 2.3 Hz, Ha-7, Ha-7′),
2.10 (2 H, td, J = 13.0, 5.0, Hz, Hb-7, Hb-7′), 1.18 (2 H, dd,
J = 12.5, 2.5 Hz, H-5, H-5′), 1.80–1.03 (16 H, m), 0.87 (6 H,
s, H-14, H-14′), 0.79 (6 H, s, H-15, H-15′), 0.59 (6 H, s, H-
16, H-16′). 13C NMR (100 MHz,CDCl3): δ = 175.22 (s, C-
12), 159.95 (s, C-17), 159.34 (d, C-18), 159.34 (d, C-20),
148.92 (s, C-8), 120.20 (d, C-19), 106.41 (t, C-13), 55.12 (d,
C-5), 51.90 (d, C-9), 42.05 (t, C-3), 39.03 (t, C-1), 38.90 (s,
C-10), 37.54 (t, C-7), 34.38 (t, C-11), 33.56 (q, C-14), 33.49
(s, C-4), 23.97 (t, C-6), 21.73 (q, C-15), 19.25 (t, C-2), 14.63
(q, C-16).
(30) Typical Procedure for the Synthesis of
Bicyclohomofarnezenic Acid Derivatives with Diazine
Skeleton – Method II
A solution of DCC (215 mg, 1.04 mmol), DMAP (100 mg,
0.82 mmol), aminodiazine 6a–c (0.84 mmol), and the acid 4
(100 mg, 0.40 mmol) in CH2Cl2 (4 mL) was stirred at r.t. for
an appropriate period of time [10 h for 4-aminopyrimidine
(6a), 28 h for aminopyrazine (6b), 5 h for 2-
aminopyrimidine (6c)]. A precipitate was filtered off,
washed with CH2Cl2, and the filtrate was evaporated under
reduced pressure. The residue was dissolved in CHCl3 (5
mL) and was purified by flash chromatography on silica
(CHCl3). The following supplementary operations and
remarks were to be pointed out in the case of reaction
products derived from amine 6c: elution with CHCl3 gave a
mixture of the bisacylamide 8 and the urea 9. For the
separation of these compounds, the mixture was extracted
first with PE. The undissolved precipitate was filtered off
and washed thoroughly with PE when the bisacylamide 8
was obtained. The filtrate solution was evaporated to dryness
and the residue crystallized from MeCN giving urea 9. The
remaining silica from the first flash chromatography was
washed with CHCl3 affording a mixture of the monoacyl
amide 7c and dicyclohexylurea 10. This mixture was
extracted with Et2O. The undissolved precipitate of
dicyclohexylurea 10 was filtered off, and the ether filtrate
was concentrated to dryness. The obtained residue was
crystallized from MeCN to give the monoacyl amide 7c.
(31) Δ8,13-Bicyclohomofarnezenic Acid Amide (7c)
White crystals; mp 149–150 °C. [α]D26 –14.8 (c 0.6, CHCl3).
IR: 3262, 3189, 3111 (NH amide), 3078, 892 (semicyclic
methylene), 1725 (C=O, amide), 1649, 1574, 1435, 1155
(pyrimidine cycle) cm–1. 1H NMR (400 MHz, CDCl3): δ =
8.60 (2 H, d, J = 8.0 Hz, H-18, H-20), 8.51 (1 H, br s, NH),
6.99 (1 H, t, J = 4.9 Hz, H-19), 4.79 (1 H, s, Ha-13), 4.54 (1
H, s, Hb-13), 2.95 (1 H, dd, J = 16.6, 10.1 Hz, Ha-11), 2.79
(1 H, dd, J = 16.6, 3.7 Hz, Hb-11), 2.56 (1 H, dd, J = 10.1,
3.7 Hz, H-9), 2.41 (1 H, ddd, J = 13.0, 4.0, 2.4 Hz, Ha-7),
2.15 (1 H, td, J = 13.0, 4.0 Hz, Hb-7), 1.26 (1 H, dd, J = 12.6,
2.1 Hz, H-5), 1.80–1.10 (8 H, m), 0.90 (3 H, s, H-14), 0.83
(33) N-Δ8,13-Bicyclohomofarnezenoyl-N,N′-Dicyclohexylurea
(10)
White crystals; mp 166–167 °C. [α]D26 11.9 (c 1.34, CHCl3).
IR: 3266 (NH amide), 3074, 879 (semicyclic methylene),
1698 (C=O amide), 1658 (C=O amide) cm–1. 1H NMR (400
MHz, CDCl3): δ = 6.47 (1 H, br s, NH), 4.75 (1 H, s, Ha-13),
4.43 (1 H, s, Hb-13), 4.02 (1 H, m, H-17), 3.72 (1 H, m, H-
24), 2.49 (3 H, m, Ha-11, Hb-11, H-9), 2.38 (1 H, ddd,
J = 12.9, 3.8, 2.2 Hz, Ha-7), 2.13 (1 H, td, J = 12.9, 4.9 Hz,
Hb-7), 2.05–1.05 (28 H, m), 1.22 (1 H, dd, J = 12.7, 2.1 Hz,
H-5), 0.90 (3 H, s, H-14), 0.82 (3 H, s, H-15), 0.71 (3 H, s,
H-16). 13C NMR (100 MHz, CDCl3): δ = 172.51 (s, C-12),
154.32 (s, C-23), 149.45 (s, C-8), 105.97 (t, C-13), 55.15 (d,
C-5), 52.09 (d, C-9), 49.86 (d, C-17), 49.13(d, C-24), 42.04
(t, C-3), 39.09 (t, C-1), 39.02 (s, C-10), 37.68 (t, C-7), 33.56
(q, C-14), 33.50 (s, C-4), 32.80 (t, C-25 and C-29), 31.55 (t,
C-11), 31.22 (t, C-22), 30.69 (t, C-18), 26.25 (t, C-19 and C-
21), 25.48 (t, C-27), 25.40 (t, C-20), 24.73 (t, C-26 and C-
28), 24.05 (t, C-6), 21.73 (q, C-15), 19.29 (t, C-2), 14.81 (q,
C-16).
Synlett 2013, 24, 697–700
© Georg Thieme Verlag Stuttgart · New York