78
J. JIANG AND Y. JI
ppm), d: 159.8, 155.9, 135.4, 115.8 (2C), 115.0, 114.8 (2C), 62.6, 55.6, 14.3; MS=EI
m=z ¼ 256.1(Mþ).
Ethyl 1-(4-Methoxyphenyl)-7-oxo-6-(4-(2-oxopiperidin-1-yl)phenyl)-
4,5,6,7-tetrahydro-1H-pyrazolo[3,4-c]pyridine-3-carboxylate (2)[7]
Compound 4 (1.42 g, 4.0 mmol), triethylamine (1.7 mL, 12 mmol), and potassium
iodide (0.064g, 0.4mmol) ware added to a solution of 3 (1.13 g, 4.4 mmol) in ethyl acet-
ate (40mL) at room temperature. The mixture was stirred for 6 h under reflux and then
cooled to 0 ꢀC. The resulting mixture was added dropwise with 4.0 N hydrochloric acid
(5 mL, 20 mmol) and stirred at room temperature for 2 h. Thereafter, water (10 mL) was
added to the mixture to separate the organic layer. The aqueous layer was extrated with
ethyl acetate (3 ꢁ 10 mL), and then the combined organic extracts were washed with
brine (2 ꢁ 10 mL), dried over anhydrous sodium sulfate, and concentrated to dryness.
Recrystallization of the residue from ethyl acetate and drying in vacuo afforded 2 as
a pale yellow solid. Yield: 1.46 g, 75%; mp 120–124ꢀC; IR (KBr, cmꢂ1): 2936 and
=
2873 (C-H aliphatic), 1711 (C N stretching), 1658 (C O stretching), 1609 (aliphatic
=
=
=
C C), 1558, 1513, 1482 and 1460 (aromatic C C), 1325, 1302 and 1254 (C-N stretch-
ing), 1144, 1088 and 1027 (C-O stretching), 833, 802 and 765 (Ar-H aromatic bending);
1H NMR (500 MHz, CDCl3, ppm), d: 7.49 (d, J ¼ 8.8 Hz, 2H), 7.35 (d, J ¼ 8.8Hz, 2H),
7.27 (d, J¼ 8.8 Hz, 2H), 6.93 (d, J ¼ 8.8 Hz, 2H), 4.48 (q, J ¼ 7.0 Hz, 2H), 4.15 (t,
J ¼ 3.2 Hz, 2H), 3.82 (s, 3H), 3.61 (t, J¼ 5.6 Hz, 2H), 3.33 (t, J¼ 6.8 Hz, 2H), 2.57 (t,
J ¼ 5.6Hz, 2H), 1.94–2.00 (m, 4H), 1.45 (t, J ¼ 7.0 Hz, 3H); 13C NMR (125 MHz,
CDCl3, ppm), d: 170.8, 162.8, 160.5, 157.9, 142.1, 140.6, 139.7, 133.7, 133.2, 127.63
(2C), 127.56, 127.44 (2C), 126.9 (2C), 114.3 (2C), 61.9, 56.2, 52.3, 51.6, 33.5, 24.2,
22.2, 22.1, 15.1; MS=EI m=z¼ 488.2 (Mþ).
1-(4-Methoxyphenyl)-7-oxo-6-(4-(2-oxopiperidin-1-yl)phenyl)-
4,5,6,7-tetrahydro-1H-pyrazolo[3,4-c]pyridine-3-carboxamide (1)[7]
To the advanced intermediate 2 (2.44 g, 5.0 mmol) was added 25% ammonia
water (1.5 mL, 20 mmol) in methanol (20 mL), and the mixture was heated to 65 ꢀC
for 5 h in an autoclave of 50 mL. The resulting mixture was cooled to room tempera-
ture, poured into water (30 mL), and crystalized below 0ꢀC. The precipitate was
filtrated and dried in vacuo at 50ꢀC to afford the desired product 1 as a pale white
solid. Yield: 2.09 g, 91%; mp 171–173 ꢀC; IR (KBr, cmꢂ1): 3448 and 3298 (N-H
=
stretching), 2940 (C-H aliphatic), 1669 (C N stretching), 1614 (C O stretching),
=
=
=
1544 (aliphatic C C), 1513, 1463 and 1441 (aromatic C C), 1334, 1300 and 1254
(C-N stretching), 1146, 1111, 1090 and 1024 (C-O stretching), 835, 816, 794 and
758 (Ar-H aromatic bending); 1H NMR (500 MHz, CDCl3, ppm), d: 7.48 (d,
J ¼ 8.0 Hz, 2H), 7.35 (d, J ¼ 8.0 Hz, 2H), 7.27 (d, J ¼ 8.0 Hz, 2H), 6.95 (d, J ¼ 8.0 Hz,
Hz, 2H), 5.66 (brs, 2H), 4.12 (t, J ¼ 5.6 Hz, 2H), 3.84 (s, 3H), 3.55–3.65 (m, 2H), 3.39
(t, J ¼ 5.6 Hz, 2H), 2.57 (t, J ¼ 6.2 Hz, 2H), 1.91–2.01 (m, 4H); 13C NMR (125 MHz,
CDCl3, ppm), d: 170.9, 164.4, 160.5, 158.0, 142.1, 140.6 (2C), 134.0, 133.2, 127.4 (4C),
126.9 (2C), 126.5, 114.4 (2C), 56.2, 52.3, 51.8, 33.5, 24.2, 22.1, 21.9; MS=EI
m=z ¼ 459.2 (Mþ).