3226
K. Umei et al.
Paper
Synthesis
HRMS (EI): m/z [M]+ calcd for C8H4ClF3N2O3S: 299.95832; found:
6-Methoxy-2-phenylpyrazolo[1,5-a]pyridine (1c)
299.95784.
Following the typical procedure for 1a using 3c (50.0 mg, 0.169
mmol) in DME (0.8 mL), phenylboronic acid (30.5 mg, 0.250 mmol), 2
M aq Na2CO3 (0.25 mL, 0.5 mmol), and PdCl2(PPh3)2 (11.7 mg, 16.7
μmol) gave 1c as a pale red solid; yield: 35.0 mg (92%); mp 84–85 °C.
6-Methoxypyrazolo[1,5-a]pyridin-2-ylTrifluoromethanesulfonate
(3c)
Following the typical procedure for 3a using 4c (175 mg, 1.07 mmol)
in THF (0.8 mL) and DMF (0.8 mL), NaH (52 mg, 1.3 mmol, 60% disper-
sion in oil), and Tf2NPh (460 mg, 1.29 mmol) gave 3c as a pale yellow
oil; yield: 308 mg (97%).
IR (ATR): 3048, 2929, 2837, 1713, 1645, 1517, 1466, 1379, 1323, 1280,
1198, 1157, 1128, 1025, 941, 852, 818, 756, 694, 603, 508, 421 cm–1
.
1H NMR (400 MHz, CDCl3): δ = 3.85 (s, 3 H), 6.74 (s, 1 H), 6.92 (dd, J =
9.7, 1.8 Hz, 1 H), 7.34 (tt, J = 7.3, 1.8 Hz, 1 H), 7.40 (d, J = 9.7 Hz, 1 H),
7.44 (t, J = 7.3 Hz, 2 H), 7.91–7.94 (m, 2 H), 8.09 (d, J = 1.8 Hz, 1 H).
IR (ATR): 1533, 1475, 1424, 1291, 1201, 1134, 1018 cm–1
.
1H NMR (400 MHz, CDCl3): δ = 3.83 (s, 3 H), 6.31 (s, 1 H), 7.05 (dd, J =
9.7, 2.4 Hz, 1 H), 7.38 (d, J = 9.7 Hz, 1 H), 7.95 (d, J = 2.4 Hz, 1 H).
13C NMR (100 MHz, CDCl3): δ = 56.0, 93.6, 110.9, 117.8, 118.9, 126.1,
128.1, 128.7, 133.4, 137.9, 149.2, 152.7.
13C NMR (100 MHz, CDCl3): δ = 56.1, 86.5, 111.2, 118.0, 118.8 (d, J =
LRMS (EI): m/z = 224 [M]+.
322.4 Hz), 120.8, 137.3, 149.9, 153.5.
LRMS (ESI): m/z = 297 [M + H]+.
HRMS (EI): m/z [M]+ calcd for C14H12N2O: 224.0950; found: 224.0933.
HRMS (ESI): m/z [M + H]+ calcd for C9H8F3N2O4S: 297.01569; found:
2-(4-Chlorophenyl)pyrazolo[1,5-a]pyridine (1d)
297.01604.
Following the typical procedure for 1a using 3a (50.0 mg, 0.188
mmol) in DME (1 mL), 4-chlorophenylboronic acid (44.9 mg, 0.287
mmol), 2 M aq Na2CO3 (0.3 mL, 0.6 mmol), and PdCl2(PPh3)2 (14.0 mg,
19.9 μmol) gave 1d as a colorless solid; yield: 37.9 mg (88%); mp 103–
2-Phenylpyrazolo[1,5-a]pyridine (1a); Typical Procedure
To a solution of 3a (50.0 mg, 0.188 mmol) in DME (1 mL) was added
phenylboronic acid (35.0 mg, 0.287 mmol), 2 M aq Na2CO3 (0.3 mL,
0.6 mmol), and PdCl2(PPh3)2 (14.0 mg, 19.9 μmol) at r.t. The mixture
was stirred at 90 °C for 4 h, then it was cooled to r.t., diluted with
EtOAc, and washed with water and brine. The organic layer was dried
(Na2SO4), and then concentrated in vacuo. The crude material was pu-
rified by flash column chromatography (silica gel, hexane–EtOAc,
10:1) to give 1a as a colorless solid; yield: 34.0 mg (93%); mp 99–
104 °C.
1
105 °C. H NMR spectroscopic data are identical to those reported in
the literature.15
IR (ATR): 3073, 3032, 2160, 1899, 1776, 1634, 1599, 1508, 1423, 1333,
1255, 1185, 1089, 1012, 946, 833, 772, 727, 636, 599, 509, 470 cm–1
.
1H NMR (400 MHz, CDCl3): δ = 6.74 (d, J = 6.7 Hz, 1 H), 6.76 (s, 1 H),
7.10 (t, J = 8.5 Hz, 1 H), 7.42 (d, J = 8.5 Hz, 2 H), 7.51 (d, J = 8.5 Hz, 1 H),
7.90 (d, J = 8.5 Hz, 2 H), 8.46 (d, J = 6.7 Hz, 1 H).
LRMS (EI): m/z = 228 [M]+.
HRMS (EI): m/z [M]+ calcd for C13H9ClN2: 228.0454; found: 228.0453.
IR (ATR): 3123, 3076, 3034, 1891, 1767, 1634, 1514, 1471, 1456, 1421,
1333, 1257, 1191, 1146, 1082, 1011, 947, 910, 838, 782, 759, 736,
683, 564, 506, 430 cm–1
.
2-(2-Chlorophenyl)pyrazolo[1,5-a]pyridine (1e)
1H NMR (400 MHz, CDCl3): δ = 6.72 (td, J = 7.3, 1.2 Hz, 1 H), 6.79 (s, 1
H), 7.05–7.11 (m, 1 H), 7.18–7.21 (m, 2 H), 7.34–7.39 (m, 1 H), 7.44–
7.49 (m, 1 H), 7.97 (d, J = 7.3 Hz, 2 H), 8.47 (d, J = 7.9 Hz, 1 H).
13C NMR (100 MHz, CDCl3): δ = 93.7, 111.7, 117.9, 123.4, 126.5, 128.4,
128.5, 128.7, 133.2, 141.6, 153.5.
LRMS (EI): m/z = 194 [M]+.
HRMS (EI): m/z [M]+ calcd for C13H10N2: 194.0844; found: 194.0883.
Following the typical procedure for 1a using 3a (500 mg, 1.88 mmol)
in DME (6.3 mL), 2-chlorophenylboronic acid (441 mg, 2.82 mmol), 2
M aq Na2CO3 (2.8 mL, 5.63 mmol), and PdCl2(PPh3)2 (132 mg, 0.19
mmol) gave 1e as a yellow oil; yield: 371 mg (87%). 1H NMR spectro-
scopic data are identical to those reported in the literature.8c,16
IR (ATR): 2958, 1713, 1636, 1519, 1460, 1413, 1331, 1249, 1163, 1048,
949, 850, 758, 731, 653, 564, 516, 463 cm–1
.
1H NMR (400 MHz, CDCl3): δ = 6.77 (td, J = 6.7, 1.2 Hz, 1 H), 7.03 (s, 1
H), 7.10–7.14 (m, 1 H), 7.28–7.39 (m, 2 H), 7.50 (dd, J = 7.9, 1.2 Hz, 1
H), 7.56 (d, J = 9.1 Hz, 1 H), 7.91 (dd, J = 7.9, 1.8 Hz, 1 H), 8.49 (d, J = 6.7
Hz, 1 H).
LRMS (EI): m/z = 228 [M]+.
HRMS (EI): m/z [M]+ calcd for C13H9ClN2: 228.0454; found: 228.0440.
6-Chloro-2-phenylpyrazolo[1,5-a]pyridine (1b)
Following the typical procedure for 1a using 3b (50.0 mg, 0.166
mmol) in DME (1 mL), phenylboronic acid (30.5 mg, 0.250 mmol), 2 M
aq Na2CO3 (0.25 mL, 0.5 mmol), and PdCl2(PPh3)2 (11.7 mg, 16.7 μmol)
gave 1b as a yellow solid; yield: 34.0 mg (90%); mp 117–120 °C. 1H
NMR spectroscopic data are identical to those reported in the litera-
ture.8c
6-Chloro-2-(4-fluorophenyl)pyrazolo[1,5-a]pyridine (1f)
IR (ATR): 3068, 2557, 2164, 1947, 1898, 1756, 1697, 1634, 1534, 1506,
1461, 1379, 1309, 1194, 1131, 1060, 949, 854, 806, 755, 682, 576,
Following the typical procedure for 1a using 3b (50.0 mg, 0.166
mmol) in DME (1 mL), 4-fluorophenylboronic acid (35.0 mg, 0.250
mmol), 2 M aq Na2CO3 (0.25 mL, 0.5 mmol), and PdCl2(PPh3)2 (11.7
mg, 16.7 μmol) gave 1f as a colorless solid; yield: 37.0 mg (90%); mp
96–102 °C.
505, 423 cm–1
.
1H NMR (400 MHz, CDCl3): δ = 6.82 (s, 1 H), 7.08 (dd, J = 9.1, 1.8 Hz, 1
H), 7.38 (t, J = 7.3 Hz, 1 H), 7.46 (t, J = 7.3 Hz, 3 H), 7.94 (d, J = 7.3 Hz, 2
H), 8.52 (s, 1 H).
13C NMR (100 MHz, CDCl3): δ = 94.5, 118.1, 119.7, 125.0, 126.5, 126.6,
128.6, 128.8, 132.8, 140.0, 154.2.
LRMS (EI): m/z = 228 [M]+.
HRMS (EI): m/z [M]+ calcd for C13H9ClN2: 228.0454; found: 228.0461.
IR (ATR): 3085, 1632, 1600, 1508, 1456, 1222, 1156, 1092, 1014, 949,
940, 803, 764, 642, 576, 518 cm–1
.
1H NMR (400 MHz, CDCl3): δ = 6.76 (s, 1 H), 7.08 (dd, J = 9.4, 1.5 Hz, 1
H), 7.14 (t, J = 8.5 Hz, 2 H), 7.46 (d, J = 9.1 Hz, 1 H), 7.91 (dd, J = 8.5, 5.4
Hz, 2 H), 8.50 (s, 1 H).
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2015, 47, 3221–3230