196
BERZIN et al.
17.27 g (85%) of (II), mp 122–124°ë. Another 0.87 g of added to the residue, and the mixture was cooled to
compound (II) was isolated from the mother liquor; 0°ë. After 30 min, the precipitate formed was filtered,
total yield 18.14 g (89%); HPLC (A): RT 5.40 (100%); washed with isopropanol (30 ml), and dried to give
IR, cm–1: 3110 (=ë–ç), 1710 (ë=é), 1630, 1595 (N=N, 31.9 g (84.6%) of the product with mp 209–212°ë. This
C=N), 1190, 1060, 1010 (ë–é–ë) cm–1. Mass specter, product was dissolved in acetonitrile (200 ml) at heat-
m/z: calculated for ë16ç19N8O7 [M + H]+ 435.3460, ing, the solution was filtered through the column with
found 435.2828; calculated for C15H19N7O7 [(M + H)+·– alumina (20 g); the column was eluted with acetonitrile
CN]+ 409.3614, found 409.3298; calculated for (100 ml), the resulting filtrates were concentrated, and
1
C11H15O7 [Sug]+ 259.2375, found 259.1898; H NMR: the residue was crystallized from ethanol (750 ml) to
8.513 (1 H, br. s, NH), 8.508 (2 H, br. s, exchangeable give 30.4 g (80.7%) of compound (IV), mp 210–212°ë;
NH2), 8.4 (1 H, s, H8), 6.24 (1 H, d, J = 4.5 Hz, H1'), HPLC (C): RT 4.30 (100%); Mass spectra, m/z: calcu-
5.89 (1 H, t, J1 = 4.5 Hz, J2 = 6.1 Hz, H2'), 5.67 (1 H, lated for ë16H19FN5O7 [M + H]+ 412.3575, found
dd, J1=J2 = 6.1 Hz, H3'), 4.41–4.31 (3 H, m, H4', H25'), 412.2708; calculated for ë16ç18FN5O7Na [M + Na]+
2.14 (3 H, s, COCH3), 2.048 and 2.040 (2 × 3 H, 2 s, 434.3394, found 434.2558; calculated for ë11ç15é7
2COCH3).
2-Fluoro-6-azido-9-(2,3,5-tri-O-acetyl-b-D-ribo-
[Sug]+ 259.2375, found 259.1648; 1H NMR: 8.33 (1 H,
s, H8), 7.90 (2 H, s, NH2), 6.11 (1 H, d, J = 5.9 Hz, H1'),
5.90 (1 H, t, J1 = J2 = 5.7 Hz, H2'), 5.57 (1 H, dd, H3'),
4.40–4.23 (3 H, m, H4', H25'), 2.10 (3 H, s, COCH3),
2.01 and 2.00 (2 × 3 H, 2 s, 2COCH3) [12].
2-Fluoroadenosine (V) was obtained according to
the procedure reported in [12] from 33.35 g (117 mmol)
of compound (IV) in methanol (1.25 l) saturated with
anhydrous ammonia, yield 21.17 g (91.6%); mp 237–
238°ë; HPLC (D): RT 4.40 (100%); MS, m/z: calcu-
lated for ë10ç13FN5O4 [M + H]+ 286.2455, found
286.2138; calculated for C10H12FN5O4Na [M + Na]+
308.2273, found 308.2038.
furanosyl)purine (III). One hundred milliliters of
65% HF/Py preliminarily cooled to –25°ë was added to
compound (II) (50 g, 115 mmol), preliminarily cooled
to –25°ë in a noncorrosive vessel. The mixture was
stirred for 10 min, TBN (27 ml, 226 mmol) was added
dropwise at the aforementioned temperature, the reac-
tion mixture was stirred until the completion of the
release of gaseous compounds, and the resulting solu-
tion was poured down to a mixture of chloroform (0.5 l)
and broken ice (0.5 kg). The resulting layers were sep-
arated; the aqueous layer was extracted with chloro-
form (0.5 l), the combined chloroform extract was
sequentially washed with water (2 × 250 ml), 5% aque-
ous sodium bicarbonate (2 × 250 ml) and water (2 ×
250 ml), and dried with magnesium sulfate. The drying
agent was filtered off and the solution was purified by
flash chromatography on alumina (200 g). The column
with the absorbent was eluted with chloroform (0.5 l);
the eluates were combined and concentrated in a vac-
uum to give 40.1 g (80%) of chromatographically
homogenous azide (III) as a foam; HPLC (B): RT 5.80
(100%); IR, cm–1: 3085, 2910 (=C−H), 2100 (N3), 1710
(C=O), 1595, 1570 (N=N, C=N), 1200, 1066, 1010 (C–
O–C); MS, m/z: calculated for ë16ç16FN7O7Na [M +
Na]+ 460.3374, found 460.2998; calculated for
ë15H17FN6O7 [(M + H)+–CN]+ 412.3378, found
412.2628; calculated for ë11ç15é7 [Sug]+ 259.2375,
found 259.1758; 1H NMR: 8.7 (1 H, s, H8), 6.25 (1 H,
d, J = 5.1 Hz, H1'), 5.92 (1 H, t, J1=J2 = 5.1 Hz, H2'),
5.59 (1 H, dd, J1=5.1 Hz, J2=5.3 Hz, H3'), 4.42–4.38 (3
H, m, H4', H25'), 2.11 (3 H, s, COCH3), 2.02 and 2.012
(2 × 3 H, 2 s, 2COCH3).
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2-Fluoro-6-amino-9-(2,3,5-tri-O-acetyl-b-D-ribo-
furanosyl)purine (IV). A solution of 2-fluoroazide
(IV) (40.1 g, 97.7 mmol) in ethyl acetate (200 ml) was
added to a solution of 10% TFA in ethyl acetate (1.4 l)
containing 10% Pd/C (0.57 g) and saturated with
hydrogen. The reaction mixture was stirred for 14 h
under hydrogen. When the rate of hydrogen absorption
decreased, TFA (30 ml) was added to the reaction mix-
ture and hydrogenation proceeded until completion of
the process. The reaction mixture was filtered, the fil-
trate was concentrated at 40°ë, isopropanol (50 ml) was
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RUSSIAN JOURNAL OF BIOORGANIC CHEMISTRY Vol. 35 No. 2 2009