736
V. O. Iaroshenko et al.
PAPER
1H NMR (DMSO-d6): d = 1.28 (s, 3 H, CH3), 1.50 (s, 3 H, 3-CH3),
1 H, CH), 5.81 (br s, 1 H, CH), 6.12 (tt, 2JH–F = 53.0 Hz, 3JH–F = 5.1
Hz, 1 H, CF2H), 6.17 (d, JH–H = 2.0 Hz, 1 H, CH), 7.60 (s, 1 H,
CH), 12.15 (br s, 1 H, NH).
2
3
3
3.54 (dd, JH–H = 12.8 Hz, JH–H = 3.2 Hz, 1 H, CH), 3.74 (dd,
2JH–H = 12.8 Hz, 3JH–H = 2.7 Hz, 1 H, CH), 4.19 (s, 1 H, OH), 4.38
(br s, 1 H, CH), 4.96 (d, 3JH–H = 5.9 Hz, 1 H, CH), 5.16 (d, 3JH–H
=
13C NMR (CDCl3): d = 11.4, 25.0, 25.3, 27.1, 64.1, 82.4, 85.6, 88.5,
6.2 Hz, 1 H), 5.32 (d, 3JH–H = 2.4 Hz, 1 H), 5.44 (d, 3JH–H = 3.9 Hz,
1 H), 5.81 (d, 3JH–H = 2.8 Hz, 1 H, CH), 6.11 (t, 3JH–F = 55 Hz, 1 H,
CF2H), 7.38 (s, 1 H, CH).
2
1
91.5 (t, JC–F = 24.0 Hz), 91.6, 91.9, 109.2 (tt, JC–F = 250 Hz,
2JC–F = 34.3 Hz), 109.7 (tt, JC–F = 258 Hz, JC–F = 26 Hz), 113.4,
1
2
136.2, 140.7, 173.0.
13C NMR (DMSO-d6): d = 25.3, 27.1, 63.7, 81.3, 85.2, 88.8, 91.1,
MS: m/z (%) = 419 (8) [M+], 401 (10), 400 (100), 390 (17), 309 (30),
297 (25), 183 (27), 179 (39), 171 (50), 149 (11), 101 (11), 84 (11),
43 (12).
1
2
102.4, 111.7, 112.8, 115.9 (t, JC–F = 240 Hz), 126.4 (t, JC–F = 25
Hz), 134.3, 142.5, 165.0.
MS: m/z (%) = 356 (3), 331 (31), 188 (15), 177 (12), 160 (22), 159
(100), 126 (17), 86 (18).
6-Ethyl-1-(2,3-O-isopropylidene-b-D-ribofuranosyl)-4-(perfluo-
robutyl)-4,7-dihydro-1H-pyrazolo[3,4-b]pyridin-4-ol (14c)
Yield: 0.78 g (71%); yellow oil; Rf = 0.20 (hexane–EtOAc, 3:1).
1-(2,3-O-Isopropylidene-b-D-ribofuranosyl)-6-methyl-4-(per-
fluoroethyl)-1H-pyrazolo[3,4-b]pyridine (13g)
Yield: 0.59 g (69%); yellow oil; Rf = 0.55 (hexane–EtOAc, 3:1).
3
1H NMR (CDCl3): d = 1.08 (t, JH–H = 7.4 Hz, 3 H, CH3), 1.29 (s,
3 H, CH3), 1.48 (s, 3 H, 3-CH3), 2.26 (q, 3JH–H = 7.4 Hz, 2 H), 3.62
1H NMR (CDCl3): d = 1.33 (s, 3 H, CH3), 1.64 (s, 3 H, 3-CH3), 2.37
(s, 3 H, CH3), 3.64 (dd, 2JH–H = 12.8 Hz, 3JH–H = 3.2 Hz, 1 H, CH),
3.88 (dd, 2JH–H = 12.8 Hz, 3JH–H = 2.7 Hz, 1 H, CH), 4.50 (br s, 1 H,
(dd, JH–H = 12.8 Hz, JH–H = 3.1 Hz, 1 H, CH), 3.86 (dd, JH–H =
3
3
2
12.8 Hz, 3JH–H = 2.0 Hz, 1 H, CH), 4.44 (br s, 1 H, CH), 4.96 (d,
3JH–H = 5.8 Hz, 1 H, CH), 5.01 (dd, 3JH–H = 5.8 Hz, 3JH–H = 3.1 Hz,
1 H, CH), 5.68 (s, 1 H, CH), 5.73 (d, 3JH–H = 2.8 Hz, 1 H, CH), 6.12
3
OH), 5.10 (dd, JH–H = 5.9 Hz, 3JH–H = 1.6 Hz, 1 H, CH), 5.23 (dd,
3
3
3
3
3JH–H = 5.5 Hz, JH–H = 2.8 Hz, 1 H, CH), 6.82 (d, JH–H = 2.8 Hz,
(d, JH–H = 2.0 Hz, 1 H, CH), 7.55 (d, JH–H = 2.0 Hz, 1 H, CH),
1 H, CH), 7.78 (s, 1 H, CH), 8.20 (s, 1 H, CH).
12.03 (br s, 1 H, NH).
13C NMR (CDCl3): d = 24.3, 25.4, 27.0, 63.0, 82.5, 85.1, 88.4, 91.7,
110.9, 111.1 (tq, 1JC–F = 215 Hz, 2JC–F = 38 Hz), 113.4, 114.5, 120.1
(qt, 1JC–F = 285 Hz, 2JC–F = 38 Hz), 132.0, 133.4 (t, 2JC–F = 25 Hz),
148.6, 152.7.
13C NMR (CDCl3): d = 11.6, 25.1, 25.8, 26.9, 64.0, 82.3, 85.4, 88.3,
91.7 (t, JC–F = 24 Hz), 91.9, 92.1, 103.2, 113.3, 136.9, 140.5, 173.2.
MS: m/z (%) = 555 (24) [M+], 525 (61), 384 (27), 383 (64), 173 (11),
164 (100), 126 (36), 83 (11), 71 (14), 69 (18), 59 (23), 43 (17).
MS: m/z (%) = 424 (22) [M+ + 1], 423 (42) [M+], 407 (19), 379 (15),
351 (17), 299 (100), 271 (67), 203 (57), 123 (11), 89 (33), 64 (20).
Methyl 3-[5-Amino-1-(2,3-O-isopropylidene-b-D-ribofurano-
syl)-1H-pyrazol-4-yl]-4,4,4-trifluoro-3-hydroxybutanoate (15a)
Yield: 0.61 g (72%); yellow oil; Rf = 0.60 (EtOAc).
Synthesis of Compounds 14, 15, 19, 23; General Procedure
A mixture of iso-AIRs 1 (2.0 mmol) and 1,3-dielectrophile (2.1
mmol) in DMF (15 mL) under an inert atmosphere was stirred for
24 h at 80 °C. The reaction mixture was then concentrated under re-
duced pressure (0.02 mmHg) and the brown oil was purified by col-
umn chromatography over silica gel.
1H NMR (CDCl3): d = 1.30 (s, 3 H, CH3), 1.47 (s, 3 H, 3-CH3), 3.21
(m, 2 H, CH2), 3.58 (dd, 2JH–H = 12.8 Hz, 3JH–H = 3.2 Hz, 1 H, CH),
3.67 (s, 3 H, OCH3), 3.89 (dd, 2JH–H = 12.8 Hz, 3JH–H = 2.6 Hz, 1 H,
CH), 4.71 (br s, 4 H, NH2 and OH), 4.90 (dd, 3JH–H = 6.0 Hz, 3JH–H
1.4 Hz, 1 H, CH), 5.20 (dd, JH–H = 6.0 Hz, JH–H = 2.6 Hz, 1 H,
CH), 5.65 (d, 3JH–H = 7.4 Hz, 1 H, CH), 5.87 (d, 3JH–H = 2.5 Hz, 1 H,
CH), 6.35 (s, 1 H, CH).
=
3
3
1-(2,3-O-Isopropylidene-b-D-ribofuranosyl)-6-methyl-4-(per-
fluoroethyl)-4,7-dihydro-1H-pyrazolo[3,4-b]pyridin-4-ol (14a)
Yield: 0.6 g (68%); yellow oil; Rf = 0.50 (hexane–EtOAc, 1:1).
13C NMR (CDCl3): d = 25.4, 26.9, 43.1, 50.9, 63.4, 73.0 (q, 2JC–F
=
1
28 Hz), 82.5, 87.9, 92.7, 98.0, 111.0, 113.9, 127.1 (q, JC–F = 278
1H NMR (CDCl3): d = 1.29 (s, 3 H, CH3), 1.49 (s, 3 H, 3-CH3), 2.00
Hz), 146.3, 147.9, 175.3.
19F NMR (CDCl3): d = –84.2.
MS: m/z (%) = 439 (9) [M+], 422 (53), 420 (26), 403 (70), 374 (47),
366 (18), 365 (90), 307 (67), 222 (50), 173 (21), 174 (100), 108
(10), 77 (34), 54 (11).
3
(s, 1 H, CH3), 2.26 (q, 3JH–H = 7.4 Hz, 2 H), 3.63 (dd, JH–H = 12.8
Hz, 3JH–H = 3.1 Hz, 1 H, CH), 3.79 (dd, 2JH–H = 12.8 Hz, 3JH–H = 2.0
3
Hz, 1 H, CH), 4.45 (br s, 1 H, CH), 4.96 (d, JH–H = 5.8 Hz, 1 H,
CH), 5.01 (dd, 3JH–H = 5.8 Hz, 3JH–H = 3.1 Hz, 1 H, CH), 5.70 (br s,
1 H, CH), 5.75 (d, 3JH–H = 2.7 Hz, 1 H), 6.11 (3JH–H = 2.0 Hz, 1 H),
7.55 (d, 3JH–H = 2.4 Hz, 1 H, CH), 12.04 (br s, 1 H, NH).
13C NMR (CDCl3): d = 20.2, 25.1, 26.9, 64.0, 82.3, 85.3, 88.3, 92.0
Methyl 3-[5-Amino-1-(2,3-O-isopropylidene-b-D-ribofurano-
syl)-1H-pyrazol-4-yl]-4,4-difluoro-3-hydroxybutanoate (15b)
Yield: 0.40 g (49%); yellow oil; Rf = 0.30 (EtOAc).
2
1
(t, JC–F = 24 Hz), 92.1, 93.8, 102.9, 107.6 (tq, JC–F = 263 Hz,
1
2
2JC–F = 37 Hz), 113.3, 118.2 (qt, JC–F = 285 Hz, JC–F = 34 Hz),
1H NMR (CDCl3): d = 1.31 (s, 3 H, CH3), 1.50 (s, 3 H, 3-CH3), 3.27
(m, 2 H, CH2), 3.57 (dd, 2JH–H = 12.7 Hz, 3JH–H = 3.2 Hz, 1 H, CH),
3.66 (s, 3 H, OCH3), 3.87 (dd, 2JH–H = 12.7 Hz, 3JH–H = 2.6 Hz, 1 H,
136.4, 140.6, 168.0.
MS: m/z (%) = 441 (24) [M+], 411 (13), 352 (14), 269 (100), 173
(13), 150 (87), 122 (13), 108 (13), 85 (13), 84 (23), 73 (12), 71 (22),
69 (26), 66 (20), 59 (31), 57 (12), 55 (12), 45 (21), 43 (24).
CH), 4.55 (br s, 4 H, NH2 and OH), 4.87 (dd, 3JH–H = 6.0 Hz, 3JH–H
=
3
3
1.4 Hz, 1 H, CH), 5.19 (dd, JH–H = 5.8 Hz, JH–H = 2.6 Hz, 1 H,
CH), 5.53 (d, 3JH–H = 7.2 Hz, 1 H, CH), 5.78 (d, 3JH–H = 2.5 Hz, 1 H,
CH), 6.39 (s, 1 H, CH), 7.17 (t, 1JH–F = 54 Hz, 1 H, CF2H).
6-Ethyl-1-(2,3-O-isopropylidene-b-D-ribofuranosyl)-4-(1,1,2,2-
tetrafluoroethyl)-4,7-dihydro-1H-pyrazolo[3,4-b]pyridin-4-ol
(14b)
13C NMR (CDCl3): d = 25.1, 26.0, 43.0, 51.1, 63.7, 70.3 (q, 2JC–F
=
1
Yield: 0.61 g (70%); yellow oil; Rf = 0.75 (hexane–EtOAc, 1:1).
27 Hz), 82.3, 87.0, 92.2, 98.0, 110.2, 113.0, 125.1 (q, JC–F = 256
1H NMR (CDCl3): d = 1.13 (t, 3JH–H = 7.4 Hz, 3 H, CH3), 1.34 (s,
Hz), 146.0, 147.2. 178.1.
3 H, CH3), 1.54 (s, 3 H, 3-CH3), 2.33 (q, 3JH–H = 7.4 Hz, 2 H), 3.67
MS: m/z (%) = 420 (12) [M+ – 1], 404 (33), 391 (44), 351 (99), 333
(100), 281 (71), 207 (10), 205 (39), 173 (29), 171 (19), 121 (11), 86
(21).
3
3
2
(dd, JH–H = 12.8 Hz, JH–H = 3.1 Hz, 1 H, CH), 3.81 (dd, JH–H
=
12.8 Hz, 3JH–H = 2.0 Hz, 1 H, CH), 4.49 (br s, 1 H, CH), 5.01 (d,
3JH–H = 5.8 Hz, 1 H, CH), 5.14 (dd, 3JH–H = 5.8 Hz, 3JH–H = 3.1 Hz,
Synthesis 2009, No. 5, 731–740 © Thieme Stuttgart · New York