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T. Aboul-Fadl et al.
PAPER
6.33 (s, 1H, H-3), 6.95 (br d, 1H, J = 6.9 Hz, H-5), 7.20 (m, 1H, H-
6), 7.49 (m, 2H, H-4 and CHCH2).
EIMS: m/z = 158 (M+).
1H NMR (360 MHz, CDCl3): = 6.61 (d, 1H, J = 2.2 Hz, H-3), 6.79
(dd, 1H, J = 7.1, 1.2 Hz, H-6), 7.16 7.26 (m, 5H, H-5 and Ph), 7.56
(dd, 1H, J = 8.9, 1.2 Hz, H-4), 7.98 (d, 1H, J = 2.2 Hz, H-2).
EIMS: m/z = 212 (M+).
Anal. Calcd. for C10H10N2 (158.1): C, 75.92; H, 6.37, N, 17.71.
Found: C, 75.93; H, 6.31; N, 17.83.
Anal. Calcd. for C13H9FN2 (212.2): C, 73.57; H, 4.27; N, 13.20.
Found: C, 73.69; H, 4.35, N, 12.97.
6-Pyrazolo[1,5-a]pyridin-7-yl-6,7,8,9-tetrahydropyrazol[1,5-
a]quinoline (8a)
7-(4-Fluorophenyl)-2-methylpyrazolo[1,5-a]pyridine (9b)
Compound 9b was prepared from 5b (258 mg, 1.0 mmol) using the
procedure described for 9a to give 181 mg (80%) as a colorless oil.
A solution of 5a (244 mg, 1.0 mmol), vinyltributyltin (417 mg, 1.25
mmol) and Pd(PPh3)2Cl2 (35 mg, 5 mol%) in NMP (2.5 mL) was
heated in a sealed tube for 16 h at 120 °C. The mixture was cooled,
treated with Bu4NF (2 mL, 1M in THF) and stirred for 2 h at r.t. Af-
ter addition of EtOAc (10 mL), the mixture was washed with H2O,
dried (Na2SO4), filtered, and evaporated under reduced pressure.
The residue was purified by flash chromatography (hexane/EtOAc,
8:2) to give 120 mg (83%) of 8a as a yellow oil.
1
IR (film): = 2925, 1630, 1503, 1307, 1233, 786 cm .
1H NMR (360 MHz, CDCl3): = 2.48 (s, 3H, CH3), 6.37 (s, 1H, H-
3), 6.68 (dd, 1H, J = 7.1, 1.3 Hz, H-6), 7.11 (dd, 1H, J = 8.8, 7.1 Hz,
H-5), 7.20 7.26 (m, 2H, Ph), 7.41 (dd, 1H, J = 8.8, 1.3 Hz, H-4),
7.91 7.95 (m, 2H, Ph).
EIMS: m/z = 226 (M+).
1
IR (film): = 2955, 1636, 1446, 1306, 789 cm .
1H NMR (360 MHz, CDCl3): = 3.07 3.17 (m, 1H, CH2-8), 3.39
3.47 (m, 2H, CH2-7), 5.27 (m, 2H, CH2-9), 6.14 (m, 1H, CH-6),
6.57 (d, 1H, J = 2.1 Hz, H-3), 6.62 (d, 1H, J = 2.1 Hz, H-3'), 6.82
(d, 1H, J = 8.9 Hz, H-5), 6.97 7.26 (m, 2H, H-5' and H-6'), 7.41 (d,
1H, J = 9.1 Hz, H-4), 7.48 (dd, 1H, J = 8.9, 1.1 Hz, H-4'), 8.02 (d,
1H, J = 2.1 Hz, H-2), 8.06 (d, 1H, J = 2.5 Hz, H-2').
13C NMR (90 MHz, CDCl3): = 29.2 (C-8), 29.3 (C-7), 38.0 (C-9),
97.2 (C-3), 97.3 (C-3'), 112.4 (C-6), 115.5 (C-5), 115.9 (C-6'),
119.2 (C-4'), 122.2 (C-4), 126.5 (C-5'), 138.3 (C-11), 139.4 (C-10
and C-13), 140.6 (C-8'), 141.2 (C-2 and C-7'), 144.4 (C-2').
Anal. Calcd. for C14H11FN2 (226.1): C, 74.31 4.90, N, 12.39. Found:
C, 74.05; H, 4.88, N, 12.48.
7-(1-Trimethylsilyl)ethynylpyrazolo[1,5-a]pyridine (10a)
Ethynyltrimethylsilane (118 mg, 1.2 mmol) was added to a stirred
mixture of 5a (244 mg, 1.0 mmol), CuI (13 mg, 7 mol%), Pd(PPh3)4
(27 mg, 5 mol%) and ethyldimethylamine (219 mg, 3.0 mmol) in
THF (10 mL). Stirring was continued for 1 h at r.t., and the solvent
was evaporated under reduced pressure. After addition of hexane
(15 mL), the mixture was filtered through a layer of Celite and con-
centrated under reduced pressure. The residue was purified by flash
chromatography (hexane/EtOAc, 95:5) to give 150 mg (70%) of
10a as a colorless oil.
EIMS: m/z = 288 (M+).
Anal. Calcd. for C18H16N4 (288.1): C, 74.98; H, 5.59, N, 19.43.
Found: C, 74.67; H, 5.77; N, 19.26.
1
IR (film): = 3077, 2960, 2161, 1619, 1517, 1307, 787 cm .
1H NMR (360 MHz, CDCl3): = 0.34 [s, 9H, Si(CH3)3], 6.59 (d,
1H, J = 2.3 Hz, H-3), 7.04 7.26 (m, 2H, H-5 and H-6), 7.55 (br d,
1H, J = 8.9 Hz, H-4), 8.05 (d, 1H, J = 2.3 Hz, H-2).
2-Methyl-6-(2-methylpyrazolo[1,5-a]pyridin-7-yl-6,7,8,9-tet-
rahydropyrazol[1,5-a]quinoline (8b)
Compound 8b was prepared from 5b (258 mg, 1.0 mmol) using the
procedure described for 8a to give 120 mg (76%) as a yellow oil.
EIMS: m/z = 214 (M+).
1
IR (film): = 2927, 1637, 1489, 1295, 788 cm .
2-Methyl-7-(1-trimethylsilyl)ethynylpyrazolo[1,5-a]pyridine
(10b)
Compound 10b was prepared from 5b (258 mg, 1.0 mmol) using the
procedure described for 10a to give 151 mg (66%) as a colorless oil.
1H NMR (360 MHz, CDCl3): = 2.55 (s, 3H, CH3), 2.56 (s, 3H,
CH3), 3.04 3.12 (m, 1H, CH2-8), 3.33 3.40 (m, 2H, CH2-7), 5.20
(m, 2H, CH2-9), 6.01 (m, 1H, CH-6), 6.32 (s, 1H, H-3), 6.36 (s, 1H,
H-3'), 6.75 (d, 1H, J = 9.1 Hz, H-5), 6.87 (dd, 1H, J = 1.7, 7.1 Hz,
H-6'), 7.26 7.34 (m, 3H, H-4' and H-5).
13C NMR (90 MHz, CDCl3): = 14.1 (CH3), 14.2 (CH3), 25.0 (C-
8), 25.5 (C-7), 37.8 (C-9), 96.6 (C-3 and C-3'), 111.4 (C-6), 114.5
(C-5), 115.1 (C-6'), 122.7 (C-4'), 122.9 (C-4), 126.2 (C-5'), 137.8
(C-11), 138.0 (C-10), 140.6 (C-8'), 141.7 (C-13), 143.8 (C-7'),
151.0 (C-2), 151.1 (C-2').
1
IR (film): = 3077, 2960, 2161m, 1619, 1517, 1307, 787 cm .
1H NMR (360 MHz, CDCl3): = 0.34 [s, 9H, Si(CH3)3], 2.53 (s,
3H, CH3), 6.34 (s, 1H, H-3), 6.94 7.26 (m, 2H, H-5 and H-6), 7.41
(br d, 1H, J = 8.9 Hz, H-4).
EIMS: m/z = 228 (M+).
7-Ethynylpyrazolo[1,5-a]pyridine (11a)
EIMS: m/z = 316 (M+).
A solution of 10a (107 mg, 0.5 mmol) in THF (5 mL) was treated
with Bu4NF (1 mL, 1 M in THF, 1.0 mmol) and stirred for 30 min
at r.t. After addition of aq NaHCO3 (5%, 10 mL), the mixture was
extracted with Et2O (3 x 10 mL). The organic layer was dried
(Na2SO4), filtered, and evaporated under reduced pressure. The res-
idue was purified by flash chromatography (hexane/EtOAc, 8:2)
yielding 55 mg (80%) of 11a as a colorless oil.
Anal. Calcd. for C20H20N4 (316.2): C, 75.92; H, 6.37, N, 17.71.
Found: C, 75.62; H, 6.43; N, 17,58.
7-(4-Fluorophenyl)pyrazolo[1,5-a]pyridine (9a)
A solution of 5a (244 mg, 1.0 mmol) and Pd(PPh3)4 (54 mg, 0.1
mmol) in toluene (10mL) was stirred for 30 min at r.t. After addition
of 4-fluorophenylboronic acid (210 mg, 1.5 mmol) in EtOH (30
mL), the mixture was treated with sat. NaHCO3 (15 mL), refluxed
for 3 h, cooled to r.t., and poured into sat. NaCl. The aqueous layer
was separated and washed with EtOAc (30 mL). The organic layer
was dried (Na2SO4), filtered, and evaporated under reduced pres-
sure. The residue was purified by flash chromatography (hexane/
EtOAc, 8:2) to give 180 mg (85%) of 9a as a colorless oil.
1
IR (film): = 3287, 3202, 2109, 1620, 1517, 1309, 788 cm .
1H NMR (360 MHz, CDCl3): = 3.79 (s, 1H, ArCCH), 6.62 (d, 1H,
J = 2.4 Hz, H-3), 7.05 7.10 (m, 2H, H-5 and H-6), 7.45 (br d, 1H,
J = 9.0 Hz, H-4), 8.05 (d, 1H, J = 2.4 Hz, H-2).
EIMS: m/z = 142 (M+).
Anal. Calcd. for C9H6N2 (142.1): C, 76.04; H, 4.25; N, 19.71.
Found: C, 76.35; H, 4.01, N, 19.55.
1
IR (film): = 3079, 1631, 1503, 1307, 1223, 786 cm .
Synthesis 2000, No. 12, 1727–1732 ISSN 0039-7881 © Thieme Stuttgart · New York