EXPERIMENTAL
1H NMR spectra were taken on a Bruker AV-300 instrument (300 MHz) using CDCl3 with TMS as
internal standard and IR spectra on a Vector 22 instrument as a film (compound 1b) or as KBr tablets
(compounds 2b, 3, 4). Melting points were measured on a Koffler stage. High resolution mass spectra were
taken on a Finnigan MAT 8200 instrument (EI, 70 eV). Elemental analysis was performed on a Carlo Erba
(Italy) model 1106 CHN analyzer. Commercially available PdCl2(PPh3)2 and 2-methyl-3-butyn-2-ol were
obtained from the Aldrich company.
Methyl 2-[(1,5-dimethyl-1H-pyrazol-4-yl)ethynyl]benzoate (1b). Methyl o-iodobenzoate (1.31 g,
5 mmol), CuI (0.01 g, 0.1 mmol), Pd(PPh3)2Cl2 (0.02 g, 0.06 mmol), PPh3 (0.04 g, 0.3 mmol), triethylamine
(3.0 ml, 4.35 g, 43 mmol), and (1,5-dimethyl-4-pyrazolyl)acetylene (0.72 g, 6 mmol) were added successively
with stirring to benzene (30 ml) in a stream of argon. The mixture was held under an argon stream for 5 h
40 min at 80ºC. Monitoring of the reaction was carried out by TLC (chloroform). At the end of the reaction the
mixture was cooled to 25ºC, filtered through a layer of aluminium oxide (20×20 mm) and SiO2 (10×20 mm),
washed initially with benzene (2×5 ml) and then ethyl acetate (3×5 ml), and the solvent was distilled off. The
20
product was dried in a desiccator over KOH to give the product 1b (1.51 g, 97%) with nD 1.6195. IR
1
spectrum, ν, cm-1: 1728.4 (C=O), 2209.6 (C≡C). H NMR spectrum, δ, ppm (J, Hz): 2.46 (3H, s, CH3); 3.82
(3H, s, NCH3); 3.94 (3H, s, OCH3); 7.32 (1H, t, J = 7.5, H-5); 7.52 (1H, t, J = 6.2, H-4); 7.58-7.59 (2H, m, H-3,
Hpyrazole); 7.94 (1H, d, J = 7.9, H-6). Mass spectrum, m/z: 254.1049 [M]. C15H14N2O2. Calculated M 254.1046.
Found, %: C 71.22; H 5.53; N 11.22. C15H14N2O2. Calculated, %: C 70.85; H 5.55; N 11.02.
Methyl 2-[(4-methoxyphenyl)ethynyl]benzoate (1a) was prepared similarly to 1a, yield 2.5 g (95%),
mp 65-67ºC (hexane) (mp 67-69ºC [7]).
2-[(1,5-Dimethyl-1H-pyrazol-4-yl)ethynyl]benzohydrazide (2b). Hydrazine hydrate (80%, 0.21 g,
4.2 mmol) was added to a solution of ester 1b (0.72 g, 2.8 mmol) in ethanol (5 ml) and was refluxed for 8 h 35
min (TLC monitoring). The mixture was cooled to 25ºC and the precipitate formed was filtered off and
recrystallized from ethyl acetate (7 ml) to give the product (0.61 g, 85%) with mp 109-110ºC. IR spectrum, ν,
1
cm-1: 1641.2 (C=O), 2204.2 (C≡C). H NMR spectrum, δ, ppm (J, Hz): 2.39 (3H, s, CH3); 2.72 (2H, s, NH2);
3.81 (3H, s, NCH3); 7.35-7.55 (3H, m, H-3,4,5arom); 7.58 (1H, s, Hpyrazole); 7.98 (1H, d, J = 8.0, H-6); 8.53 (1H, s,
NH). Mass spectrum, m/z: 254.1157 [M]. C14H14N4O. Calculated: M 254.1167. Found, %: C 66.62; H 5.75;
N 10.37. C14H14N4O2. Calculated, %: C 66.13; H 5.55; N 22.02.
2-Amino-3-(4'-methoxybenzylidene)isoindolin-1-one (3). Hydrazine hydrate (80%, 0.4 g, 10 mmol)
was added to a solution of ester 1a (1 g, 3.8 mmol) in ethanol (5 ml) and was refluxed for 14 h 50 min
(monitoring by TLC, CH2Cl2–AcOEt, 1:1). The mixture was cooled to 25ºC and the precipitate formed was
filtered off and recrystallized from ethanol (25 ml) to give the product 3 (0.67 g, 67%) with mp 140-141ºC. IR
1
spectrum, ν, cm-1: 1641.2 (C=O), 2204.2 (C≡C). H NMR spectrum, δ, ppm (J, Hz): 3.78 (3H, s, OCH3); 4.35
(2H, s, NH2); 6.65 (1H, s, =CH); 6.85 (2H, d, J = 8.7, H o,o'-Ph); 7.65 (2H, d, J = 8.7, H m, m'-Ph); 7.65-7.84
(4H, m, H-4,5,6,7). Mass spectrum, m/z 266.1048 [M]. C16H14N2O2. Calculated: M 266.1050. Found, %:
C 72.05; H 5.46; N 10.52. C16H14N2O2. Calculated, %: C 72.16; H 5.30; N 10.52.
4-[(1,5-Dimethyl-1H-pyrazol-4-yl)methyl]phthalazin-1(2H)-one (4) KOH (60 mg, 110 mmol) was
added to a solution of hydrazide 2b (100 mg, 39 mmol) in ethanol (5 ml) and the product was refluxed for 15 h
(monitoring by TLC, AcOEt). The mixture was cooled to 25ºC and the precipitate formed was filtered off and
recrystallized from ethanol to give the product 4 (70 mg, 70%) with mp 236-238ºC. IR spectrum, ν, cm-1: 1675
(C=O). 1H NMR spectrum, δ, ppm: 2.21 (3H, s, CH3); 3.73 (3H, s, NCH3); 4.03 (2H, s, CH2); 7.70-7.85 (4H, m,
H-5,6,7,8); 9.93 (1H, s, NH). Mass spectrum, m/z: 254.1155 [M]. C14H14N4O. Calculated: M 254.1167. Found,
%: C 66.42; H 5.63; N 22.23. C14H14N4O. Calculated, %: C 66.13; H 5.55; N 22.20.
This work was carried out with the financial support of the grant RUX0-008-NO-06/BP2M08, Russian
Fund for Basic Research No. 07-03-00048a and with the integrated grant No 54 and Chemical Service Center of
the Siberian Branch of the Russian Academy of Sciences.
57