References and Notes
<A NAME="RD27408ST-1A">1a</A>
De Clercq E.
Antiviral Res.
2005,
67:
56
<A NAME="RD27408ST-1B">1b</A>
Jordheim L.
Calmarini CM.
Dumontet C.
Lancet
Oncol.
2002,
3:
415
<A NAME="RD27408ST-1C">1c</A>
Nabhana C.
Gartenhaus RB.
Tallman MS.
Leukemia Res.
2004,
28:
429
<A NAME="RD27408ST-2A">2a</A>
Cristalli G.
Costanzi S.
Lambertucci C.
Taffi S.
Vittori S.
Volpini R.
Farmaco
2003,
58:
193
<A NAME="RD27408ST-2B">2b</A>
Sanghvi YS. In
Antisense Research
and Applications
Crooke ST.
Lebleu B.
CRC Press;
Boca
Raton FL:
1993.
p.273-288
<A NAME="RD27408ST-2C">2c</A>
Kool ET.
Morales JC.
Guckian
KM.
Angew. Chem. Int. Ed.
2000,
39:
990
<A NAME="RD27408ST-3A">3a</A>
Kojima N.
Inoue K.
Nakajima-Shibata R.
Kawahara S.
Ohtsuka E.
Nucleic Acids Res.
2003,
31:
7175
<A NAME="RD27408ST-3B">3b</A>
Mizusawa S.
Nishimura S.
Seela F.
Nucleic
Acids Res.
1986,
14:
1319
<A NAME="RD27408ST-4A">4a</A>
Cook DP.
Rousseau RJ.
Mian AM.
Meyer
RB.
Dea P.
Ivanovics G.
Streeter DG.
Witkowski JT.
Stout MG.
Simon LN.
Sidwell RW.
Robins
RK.
J.
Am. Chem. Soc.
1975,
97:
2916
<A NAME="RD27408ST-4B">4b</A>
Liu M.-C.
Luo M.-Z.
Mozdziesz DE.
Lin T.-S.
Dutschman GE.
Gullen EA.
Cheng Y.-C.
Sartorelli AC.
Nucleosides, Nucleotides
Nucleic Acids
2001,
22:
1975
<A NAME="RD27408ST-5">5</A>
Girgis NS.
Michael MA.
Smee DF.
Alaghamandan HA.
Robins RK.
Cottam HB.
J. Med. Chem.
1990,
33:
2750
<A NAME="RD27408ST-6A">6a</A>
Wu O.
Simons C.
Synthesis
2004,
1533
<A NAME="RD27408ST-6B">6b</A>
Watanabe KA. In
Chemistry of Nucleosides
and Nucleotides
Vol. 3:
Townsend LB.
Plenum Press;
New
York:
1994.
p.421-535
<A NAME="RD27408ST-6C">6c</A>
Von Krosigk U.
Benner
SA.
J. Am. Chem.
Soc.
1995,
117:
5261
<A NAME="RD27408ST-6D">6d</A>
Matulic-Adamic J.
Beigelman L.
Portmann S.
Egli M.
Usman N.
J.
Org. Chem.
1996,
61:
3909
<A NAME="RD27408ST-6E">6e</A>
Hilbrand S.
Blaser A.
Parel PS.
Leumann CJ.
J. Am. Chem. Soc.
1997,
119:
5499
<A NAME="RD27408ST-7A">7a</A>
Kourafalos VN.
Marakos P.
Pouli N.
Townsend
LB.
Synlett
2002,
1479
<A NAME="RD27408ST-7B">7b</A>
Kourafalos VN.
Marakos P.
Pouli N.
Townsend LB.
J.
Org Chem.
2003,
68:
6466
<A NAME="RD27408ST-7C">7c</A>
Korouli S.
Lougiakis N.
Marakos P.
Pouli N.
Synlett
2008,
181
<A NAME="RD27408ST-8">8</A>
Chapman D.
Hurst J.
J. Chem. Soc., Perkin Trans.
1
1980,
2398
<A NAME="RD27408ST-9">9</A>
Marakos P.
Pouli N.
Wise D.
Townsend BL.
Synlett
1997,
561
<A NAME="RD27408ST-10">10</A>
Preparation of
1-Acetyl-5-pthalimido-7-methoxy-1
H
-pyrazolo[3,4-
c
]pyridine
(7)
Potassium acetate (77 mg, 0.78 mmol) and Ac2O
(0.15 mL, 1.56 mmol) were added under argon to a solution of the acetamide 6 (170 mg, 0.52 mmol) in dry benzene (40
mL). The reaction mixture was heated at 80 ˚C, isoamyl
nitrite (0.07 mL, 0.52 mmol) was added, and the resulting mixture was
refluxed for 10 h. The insoluble material was then filtered off,
the solvent was vacuum evaporated, and the residue was purified
by column chromatography (silica gel) using a mixture of cyclohexane-EtOAc
(60:40, v/v) as the eluent to give 7 as
a white solid (153 mg, 87%); mp >300 ˚C (EtOH). ¹H
NMR (400 MHz, CDCl3): δ = 2.84
(s, 3 H, COCH3), 4.13 (s, 3 H, OCH3), 7.82
(m, 3 H, H-4, H-4′,
H-5′), 7.98 (m,
2 H, H-3′, H-6′), 8.17 (s, 1 H, H-3). ¹³C
NMR (50 MHz, CDCl3): δ = 23.9
(CH3CO), 54.8 (OCH3),
106.3 (C-4), 123.9 (C-3′, C-6′), 124.7 (C-3a),
131.8 (C-2a′, C-6a′), 134.5 (C-4′, C-5′),
135.6 (C-7a), 138.1 (C-3), 145.5 (C-5), 151.2 (C-7), 166.9 [CO(Phth)],
168.5 (COCH3). Anal. Calcd for
C17H12N4O4: C, 60.71;
H, 3.60; N, 16.66. Found: C, 60.82; H, 3.45; N, 16.88.
<A NAME="RD27408ST-11">11</A>
Preparation of
7-Methoxy-1
H
-pyrazolo[3,4-
c
]pyridin-5-amine
(8)
Compound 7 (120 mg, 0.73
mmol) was dissolved in a sat. solution of NH3 in MeOH.
The solution was stirred at r.t. for 4 h, the solvent was vacuum
evaporated, and the residue was purified by column chromatography
(silica gel) using a mixture of cyclohexane-EtOAc (20:80,
v/v) as the eluent to give 8 (54
mg, 92%) as white crystals; mp 162-164 ˚C (EtOH). ¹H
NMR (400 MHz, CDCl3): δ = 4.07
(s, 3 H, OCH3), 5.20 (br s, 2 H, NH2, D2O
exch.), 6.29 (s, 1 H, H-4), 7.82 (s, 1 H, H-3). ¹³C
NMR (50 MHz, CDCl3): δ = 53.3 (OCH3),
86.8 (C-4), 122.9 (C-7a), 132.0 (C-3a), 132.7 (C-3), 149.1 (C-5),
149.6 (C-7). Anal. Calcd for C7H8N4O:
C, 51.21; H, 4.91; N, 34.13. Found: C, 51.43; H, 4.80; N, 34.26.
<A NAME="RD27408ST-12A">12a</A>
Olah GA.
Narang SC.
Gupta BGB.
Malhotra R.
J. Org. Chem.
1979,
44:
1247
<A NAME="RD27408ST-12B">12b</A>
Ramasany K.
Imamura N.
Robins RK.
Revankar GR.
J. Heterocycl. Chem.
1988,
25:
1893
<A NAME="RD27408ST-13">13</A>
Preparation of
5-Amino-1
H
-pyrazolo[3,4-
c
]pyridin-7 (6H
)-one (9)
Sodium
iodide (81 mg, 0.54 mmol) and TMSCl (68 µL, 0.54 mmol)
were added under argon to a solution of 8 (85
mg, 0.52 mmol) in dry MeCN (5 mL). The resulting mixture was heated
at 65 ˚C for 3 h, the precipitate was filtered, washed with
EtOAc, and it was purified by column chromatography (silica gel)
using a mixture of EtOAc-MeOH (98:2, v/v) as the
eluent to give 9 (60 mg, 77%);
mp >300 ˚C (EtOH). ¹H NMR
(400 MHz, DMSO-d
6): δ = 5.09
(br s, 2 H, NH2, D2O exch.), 5.40 (s, 1 H,
H-4, D2O exch.), 7.54 (s, 1 H, H-3), 10.50 (br s, 1 H,
N6H, D2O exch.), 13.38 (br s, 1 H, N¹H, D2O
exch.). Anal. Calcd for C6H6N4O:
C, 48.00; H, 4.03; N, 37.32. Found: C, 47.83; H, 3.95; N, 37.17.
<A NAME="RD27408ST-14">14</A>
Data for 7-Methoxy-3-(β-
d
-ribofuranosyl)-1
H
-pyrazolo[3,4-
c
]pyridin-5-amine
(15)
Mp 216-218 ˚C (EtOH). ¹H
NMR (400 MHz, CD3OD): δ = 3.72
(dd, 1 H, H-5′, J
4
′
,5
′ = 4.70
Hz, J
5
′
,5
′ = 12.13
Hz), 3.84 (dd, 1 H, H-5′, J
4
′
,5
′ = 3.52
Hz, J
5
′
,5
′ = 12.13
Hz), 4.01 (m, 1 H, H-4′), 4.04 (s, 3 H, OCH3),
4.18 (m, 1 H, H-3′), 4.31 (m, 1 H, H-2′), 5.04
(d, 1 H, H-1′, J
1
′
,2
′ = 6.65
Hz), 6.46 (s, 1 H, H-4, D2O exch.). ¹³C
NMR (50 MHz, CD3OD): δ = 53.7
(CH3O), 63.5 (C-5′), 72.7 (C-3′), 76.4
(C-2′), 80.4 (C-1′), 86.6 (C-4′), 87.9
(C-4), 124.0 (C-7a), 131.0 (C-3a), 143.2 (C-3), 150.7 (C-7). Anal.
Calcd for C12H16N4O5:
C, 48.65; H, 5.44; N, 18.91. Found: C, 48.45; H, 5.28; N, 18.83.
<A NAME="RD27408ST-15">15</A>
Data for 5-Amino-3-(β-
d
-ribofuranosyl)-1
H
-pyrazolo[3,4-
c
]pyridin-7
(6
H
)-one
(16)
Mp 158-160 ˚C (EtOH). ¹H
NMR (400 MHz, CD3OD): δ = 3.72
(dd, 1 H, H-5′, J
4
′
,5
′ = 4.70
Hz, J
5
′
,5
′ = 12.13
Hz), 3.82 (dd, 1 H, H-5′, J
4
′
,5
′ = 3.52
Hz, J
5
′
,5
′ = 12.13
Hz), 3.99 (m, 1 H, H-4′), 4.16 (m, 1 H, H-3′),
4.26 (m, 1 H, H-2′), 4.97 (d, 1 H, H-1′, J
1
′
,2
′ = 6.26
Hz), 5.81 (s, 1 H, H-4, D2O exch.). Anal. Calcd for C11H14N4O5:
C, 46.81; H, 5.00; N, 19.85. Found: C, 46.75; H, 5.12; N, 19.97.
<A NAME="RD27408ST-16A">16a</A>
Sanghvi YS.
Larson SB.
Robins RK.
Revankar GR.
J. Chem. Soc., Perkin Trans. 1
1990,
2943
<A NAME="RD27408ST-16B">16b</A>
Hadjipavlou C.
Kostakis IK.
Pouli N.
Marakos P.
Mikros E.
Tetrahedron
Lett.
2006,
47:
3681
<A NAME="RD27408ST-17">17</A>
Tsikouris O.
Bartl T.
Touek J.
Lougiakis N.
Tite T.
Marakos P.
Pouli N.
Mikros E.
Marek R.
Magn. Res. Chem.
2008,
46:
643
<A NAME="RD27408ST-18">18</A>
The AM1 calculations were performed
in combination with RHF method and a convergence criterion of 0.01
kcal mol-¹, using the Polak-Ribiere
(conjugate gradient) geometry optimization method as implemented
in the HyperChem 5.0 software (Hypercube Inc).