HETEROCYCLES

Paper | Regular issue | Vol. 92, No. 6, 2016, pp. 1075-1084
Received, 1st March, 2016, Accepted, 23rd March, 2016, Published online, 8th April, 2016.

■ Synthesis and Antimicrobial Evaluations of Novel Spiro Cyclic 2-Oxindole Derivatives of N-(1H-Pyrazol-5-Yl)-Hexahydroquinoline Derivatives

Said Ahmed Soliman Ghozlan, Muhammed Ali Ramadan, Amr Mohamed Abdelmoniem,* and Ismail Abdelshafy Abdelhamid*

Department of Chemistry, Faculty of Science, Cairo University, Giza 12613, Egypt

Abstract

A novel series of interesting spiro cyclic 2-oxindole derivatives of N-(1H-pyrazol-5-yl)hexahydroquinoline derivatives were prepared via the versatile readily accessible cyclic β-enaminones incorporating pyrazole. Antimicrobial evaluations were performed on the prepared compounds. Most of these compounds exhibited high to moderate antimicrobial activity.

introduction
The Michael addition reaction has been widely used in organic synthesis for its C–C bond forming ability. Useful application of a tandem Michael addition is seen in the total synthesis of the antimicrobial compound Claenone.1 In this respect, Yamada et al.1 managed to construct a norbornane ring using two sequential Michael additions. The Michael reaction is also used in other reactions. The best known example is the Robinson annulation, where the Michael addition occurs as the first step.2 This sequence of Michael addition followed by intramolecular Aldol has proved to be one of the most important chemical reactions introduced into in the area of steroid chemistry as shown in Woodward’s synthesis of cortisone.2 In addition, the spiro-oxindole ring system is one of the most distinguished heterocyclic ring systems, which constitutes the core structural element of many biologically active molecules that received an extensive synthetic interest.3-17 Moreover, quinoline and its derivatives exist in a variety of biologically significant compounds possessing anticancer,18 antioxidants,19 anti-inflammatory20 and antimicrobial activities.21-23 Considering the versatile bioactivities of the two structures of spiro-oxindole and 2-amino-tetrahydroquinolin-5-one, we expect that the integration of the two scaffolds into a spiro-oxindole incorporating 2-amino-tetrahydroquinolin-5-one can result in the discovery of new active drugs.

RESULTS AND DISCUSSION
In continuation to our interest on the chemistry of enamines24-27 as well as Michael addition reactions,10,28-32 we report herein a new series of novel spirocyclic 2-oxindole derivatives of N-(1H-pyrazol-5-yl)hexahydroquinoline derivatives via the cyclocondensation reaction of 3- cyanomethylidene-2-oxindoles and 3-(substituted pyrazol-5-yl)-5,5-dimethylcyclohex-2-enone. The required cyclic β-enaminoketones incorporating pyrazole moiety 3, were prepared via the reaction of the dimedone 1 with the aminopyrazole derivatives 2 using a catalytic amount of trichloroacetic acid as a catalyst under solvent-free conditions.

The possibility of [3+3] atom combination of the prepared β-enaminones 3a,b with 3- cyanomethylidene-2-oxindoles 4a-c through Michael addition reaction was studied. Thus, the reaction of compound 3a with compounds 4a-c in the presence of piperidine resulted in the formation of spiroquinolines 7a-c. Compounds 7 were formed due to the initial addition of the β-CH of 3a to the activated double bond in 4, to yield Michael adducts 5 that readily cyclized into 6 that tautomerized into 7. (cf. Scheme 2). The structures of the novel hexahydroquinolines 7 were assigned based on the spectroscopic methods. Thus, IR data of 7c indicated the absence of CN group. It also revealed two absorption bands at ν 3401 and 3246 cm-1 due to NH2 and two NH. The bands at ν 1667 and 1635 cm-1 are assigned for the two carbonyl groups. 1H NMR spectrum of 7c revealed three singlet signals at δ 0.4, 0.82 and 2.41 ppm for three methyl groups. The ester group appears as triplet at δ 0.85 ppm and quartet at δ 3.68 ppm with J = 7.2 Hz. In addition, it displayed a prominent signal at δ 9.89 for NH group. The NH2 and aromatic protons appear as multiplets in the area δ 6.62-7.53 ppm. All other signals appear at their expected position. Furthermore, 13C NMR was found to be in agreement with the proposed structure. The key signal at δ 32.3 ppm is assigned for the spiro carbon. The signals at δ 161.9 and 196.9 ppm are assigned to the two carbonyl groups. All other carbon signals appeared at their expected positions.

Conducting the above-mentioned reaction under the same conditions on the cyclic enamines 3b, carrying ester group on the pyrazole ring, leads to the formation of 8a,b. Trials to affect a further cyclization to prepare compounds 9 did not succeed.

Quinolines 7a,b were used as precursors for the synthesis of the spiro-hexacyclic products. Thus, boiling compounds 7a,b in acetic anhydride for a long period results in the formation of 10 that readily tautomerize into 11 followed by water removal to give the spiro[indoline-3,8'-pyrazolo[1',5':5,6][1,3,5]triazino[1,2-a]quinoline] derivatives 12a,b, respectively. The structures of compounds 12 were confirmed based on their spectral data. The analyses clearly indicate the absence of the NH and NH2 groups. It also revealed the presence of additional methyl group.

Antimicrobial Activity
The antibacterial activity of the synthesized compounds was screened against the Gram-positive bacteria: Streptococcus pneumoniae and Bacillus subtilis, and the Gram-negative bacteria: Pseudomonas aeruginosa and Escherichia coli using diffusion agar medium. The antifungal activity of the compounds was tested against Candia albicans and Aspergillus fumigatus using diffusion agar medium. The minimum inhibitory concentration (MIC) was carried out using microdilution susceptibility method.33 Ampicillin and Gentamycin were used as standard antibacterial drugs. Amphotericin B was used as a standard antifungal drug. The observed data of the antimicrobial activity of compounds and control drugs are given in Table 1. It is clear that, however compound 12b showed the lowest activities, most of the other screened samples, showed significant antibacterial and antifungal activities (Table 1). The MIC values were determined as the lowest concentration that completely inhibited visible growth of the microorganisms. The investigation of antibacterial screening (Table 2) reveals that most of the compounds showed excellent antibacterial activity at MIC 0.49-3.9 ??g/mL in DMSO. Amongst all the synthesized quinoline derivatives, compounds 7a, 12a and 8b exhibited good activities against Bacillus subtilis (MIC 0.24, 0.49, 0.98 ??g/mL) and Streptococcus pneumoniae (MIC 0.49, 0.98 1.95 ??g/mL) and Escherichia coli (MIC: 0.49, 0.98, 1.95 ??g/mL). On the other hand, they showed moderate activities against Pseudomonas aeruginosa (MIC: 1.95, 3.9, 3.9 ??g/mL). Compound 7c displayed moderate activities towards Bacillus subtilis, pseudomonas aeruginosa and Escherichia coli (MIC 3.9 ??g/mL). Compounds 8a and 7b revealed moderate activity towards Streptococcus pneumoniae, Bacillus subtilis and Escherichia coli. The antifungal screening study also revealed that the newly synthesized compounds showed moderate-to-good inhibition against Aspergillus fumigatus. However, all the tested compounds showed no bioactivities towards Candida albicans.

In conclusion, the Michael reaction of β-enaminones 3a,b with 3-cyanomethylidene-2-oxindoles 4a-c represents a versatile tool for the synthesis of various spirocyclic structures combining both oxindole and hexahydroquinoline fragments. The formation of spiro-polycondensed derivatives 12a,b was also achievable by the action of acetic anhydride. Preliminary antimicrobial evaluation tests indicate that the majority of the synthesized compounds showed promising antimicrobial activities.

EXPERIMENTAL
Melting points were measured with a Stuart melting point apparatus and are uncorrected. The IR spectra were recorded using a FTIR Bruker–vector 22 spectrophotometer as KBr pellets. The 1H and 13C NMR spectra were recorded in DMSO–d6 and CDCl3 as solvent on Varian Gemini NMR spectrometer at 400 MHz and 100 MHz, respectively, using TMS as internal standard. Chemical shifts are reported as δ values in ppm. Mass spectra were recorded with a Shimadzu GCMS–QP–1000 EX mass spectrometer in EI (70 eV) model. The elemental analyses were performed at the Micro analytical center, Cairo University.
Synthesis of enamines (3a,b). A mixture of dimedone 1 (1 g, 7.14 mmol) and 3-methyl-4-phenyl-1H-pyrazol-5-amine 2a (1.24 g, 7.17 mmol) or ethyl 5-amino-3-phenyl-1H-pyrazole-4-carboxylate 2b (1.65 g, 7.14 mmol) was heated in an oil bath at 120 °C in presence of trichloroacetic acid (0.2 g, 1.23 mmol) for 20 min. The oily residue was extracted with CHCl3 (25 mL). The solvent was removed at reduced pressure and the crude solid was crystallized from EtOH.
5,5-Dimethyl-3-((3-methyl-4-phenyl-1H-pyrazol-5-yl)amino)cyclohex-2-enone (3a): Yellow crystals (1.92 g, 91%), Mp 248-250 °C, IR (KBr): ν 3437, 3226 (br, 2NH), 1712 (CO2Et), 1535 (CO) cm-1, 1H NMR (400 MHz, DMSO-d6): δ 0.94 (s, 6H, 2CH3), 1.94 (s, 2H, CH2), 2.26 (s, 2H, CH2), 2.30 (s, 3H, pyrazole CH3), 5.01 (s, 1H, =CH), 7.21-7.39 (m, 5H, ArH), 8.49 (br s, 1H, enamine NH), 12.58 (br s, 1H, pyrazole NH) ppm, 13C NMR (100 MHz, CDCl3): δ 10.3 (CH3), 27.9 (2CH3), 32.3 (C), 41.8 (CH2), 50.0 (CH2), 99.2 (C), 112.0 (C), 125.9 (C), 128.1 (CH), 128.2 (CH), 132.0 (C), 138.2 (C), 152.9 (C), 161.9 (C), 196.9 (C) ppm, MS (EI, 70 eV): m/z (%) 295 ([M+], 78), 280 (99), 267 (22), 252 (25), 239 (59), 211 (100), 194 (32), 115 (32), 77 (20), Anal. Calcd for C18H21N3O: C, 73.19; H, 7.17; N, 14.23. Found: C, 73.06; H, 7.12; N, 14.11.
Ethyl 5-((5,5-dimethyl-3-oxocyclohex-1-en-1-yl)amino)-3-phenyl-1H-pyrazole-4-carboxylate (3b): Yellow crystals (2.14 g, 85%), Mp 222-224 °C, IR (KBr): ν 3429 (br, 2NH), 1675 (CO2Et), 1546 (CO) cm-1, 1H NMR (400 MHz, DMSO-d6): δ 0.99 (s, 6H, 2CH3), 1.05 (t, 3H, J = 7.2 Hz, CH3CH2), 2.10 (s, 2H, CH2), 2.46 (s, 2H, CH2), 4.12 (q, 2H, J = 7.2 Hz, CH2CH3), 6.51 (s, 1H, =CH), 7.48-7.62 (m, 5H, ArH), 8.53 (br s, 1H, enamine NH), 13.30 (br s, 1H, pyrazole NH) ppm, 13C NMR (100 MHz, CDCl3): δ 13.9 (CH3), 28.3 (CH3), 32.9 (C), 44.2 (CH2), 50.2 (CH2), 60.3 (CH2), 97.5 (C), 104.3 (CH), 127.8 (CH), 128.7 (C), 129.5 (CH), 129.8 (CH), 145.9 (C), 152.3 (C), 156.3 (C), 165.5 (C), 200.3 (C) ppm, MS (EI, 70 eV): m/z (%) 353 ([M+], 21), 338 (20), 308 (20), 238 (21), 231 (36), 217 (20), 185 (100), 181 (33), 128 (35), 96 (23), 77 (37), Anal. Calcd for C20H23N3O3: C, 67.97; H, 6.56; N, 11.89. Found: C, 67.88; H, 6.47; N, 11.82.
General method for synthesis of compounds (7a-c). A mixture of enamine 3a (0.30 g, 1 mmol) and 3-cyanomethylidene-2-oxindole derivatives 4a-c (1 mmol) was heated at reflux in absolute EtOH (15 mL) in presence of piperidine (0.2 mL) for 3 h. The crude solid was crystallized from EtOH-dioxane (3:1, v/v).
2'-Amino-7',7'-dimethyl-1'-(3-methyl-4-phenyl-1H-pyrazol-5-yl)-2,5'-dioxo-5',6',7',8'-tetrahydro-1'H-spiro[indoline-3,4'-quinoline]-3'-carbonitrile (7a): Yellow crystals (0.42 g, 85%), Mp 248-250 °C, IR (KBr): ν 3448, 3398, 3311, 3204 (2NH and NH2), 2187 (CN), 1706, 1638 (2CO) cm-1, 1H NMR (400 MHz, DMSO-d6): δ 0.44 (s, 3H, CH3), 0.82 (s, 3H, CH3), 1.71 (m, 2H, CH2), 2.08 (m, 2H, CH2), 2.44 (s, 3H, pyrazole CH3), 5.62 (br s, 2H, NH2), 6.70-7.57 (m, 9H, ArH), 10.19 (br s, 1H, oxindole NH), 13.29 (br s, 1H, pyrazole NH) ppm; 13C NMR (100 MHz, CDCl3): δ 10.3 (CH3), 25.3 (CH3), 28.8 (CH3), 31.4 (C), 48.2 (CH2), 49.3 (C), 56.3 (CH2), 61.2 (C), 108.8 (C), 110.1 (C), 116.1 (CH), 118.4 (C), 121.1 (CH), 122.5 (CH), 126.9 (CH), 127.3 (C), 128.0 (CH), 128.5 (CH), 130.4 (CH), 135.9 (C), 138.1 (C), 140.9 (C), 150.9 (C), 151.5 (C), 179.6 (C), 193.5 (C) ppm; MS (EI, 70 eV): m/z (%) 490 ([M+], 39), 482 (29), 466 (41), 394 (46), 295 (37), 143 (100), 128 (48), 75 (54), Anal. Calcd for C29H26N6O2: C, 71.00; H, 5.34; N, 17.13. Found: C, 71.13; H, 5.29; N, 17.08.
2'-Amino-1,7',7'-trimethyl-1'-(3-methyl-4-phenyl-1H-pyrazol-5-yl)-2,5'-dioxo-5',6',7',8'-tetrahydro-1'H-spiro[indoline-3,4'-quinoline]-3'-carbonitrile (7b): Yellow crystals (0.42 g, 83%), Mp 248-250 °C, IR (KBr): ν 4377, 3404, 3237 (br, 2NH and NH2), 2187 (CN), 1720, 1632 (2CO) cm-1, 1H NMR (400 MHz, DMSO-d6): δ 0.43 (s, 3H, CH3), 0.85 (s, 3H, CH3), 1.71 (m, 2H, CH2), 2.06 (m, 2H, CH2), 2.39 (s, 3H, pyrazole CH3), 3.11 (s, 3H, NCH3), 5.73 (br s, 2H, NH2), 6.74-7.57 (m, 9H, ArH), 13.25 (br s, 1H, pyrazole NH) ppm; 13C NMR (100 MHz, CDCl3): δ 9.8 (CH3), 12.1 (CH3), 24.6 (CH3), 28.2 (CH3), 30.3 (C), 47.9 (CH2), 48.7 (C), 49.5 (CH2), 57.8 (CH2), 78.4 (C), 106.9 (C), 111.9 (C), 115.5 (CH), 119.2 (CH), 121.5 (CH), 125.7 (CH), 126.2 (C), 127.2 (CH), 127.3 (C), 127.8 (CH), 129.9 (CH), 136.4 (C), 142.4 (C), 149.5 (C), 151.8 (C), 167.8 (C), 181.3 (C), 192.6 (C) ppm; MS (EI, 70 eV): m/z (%) 504 ([M+], 22), 499 (15), 384 (38), 356 (47), 305 (62), 117 (100), Anal. Calcd for C30H28N6O2: C, 71.41; H, 5.59; N, 16.66. Found: C, 71.33; H, 5.48; N, 16.58.
Ethyl 2'-amino-7',7'-dimethyl-1'-(3-methyl-4-phenyl-1H-pyrazol-5-yl)-2,5'-dioxo-5',6',7',8'-tetrahydro-1'H-spiro[indoline-3,4'-quinoline]-3'-carboxylate (7c): Yellow crystals (0.43 g, 80%), Mp 248-250 °C, IR (KBr): ν 3401, 3246 (br, 2NH and NH2), 1721 (CO2CH2CH3), 1667, 1635 (2CO) cm-1, 1H NMR (400 MHz, DMSO-d6): δ 0.40 (s, 3H, CH3), 0.82 (s, 3H, CH3), 0.85 (t, 3H, J = 7.2 Hz, CO2CH2CH3), 1.68 (m, 2H, CH2), 2.05 (m, 2H, CH2), 2.41 (s, 3H, pyrazole CH3), 3.68 (q, 3H, J = 7.2 Hz, CO2CH2CH3), 6.62-7.53 (m, 11H, ArH and NH2), 9.89 (br s, 1H, oxindole NH), 13.26 (br s, 1H, pyrazole NH) ppm; 13C NMR (100 MHz, CDCl3): δ 9.6 (CH3), 25.2 (CH3), 28.0 (CH3), 30.7 (C), 35.8 (CH3), 47.2 (CH2), 48.5 (C), 55.8 (CH2), 60.4 (C), 106.5 (C), 109.5 (C), 115.6 (CH), 120.5 (C), 121.1 (CH), 121.7 (CH), 126.3 (CH), 126.9 (C), 127.3 (CH), 127.8 (CH), 128.1 (CH), 129.6 (C), 134.2 (C), 137.6 (C), 141.7 (C), 150.4 (C), 151.0 (C), 177.3 (C), 193.2 (C) ppm; MS (EI, 70 eV): m/z (%) 537 ([M+], 2), 464 (100), 128 (62), 115 (48), 83 (57), Anal. Calcd for C31H31N5O4: C, 69.26; H, 5.81; N, 13.03. Found: C, 69.18; H, 5.77; N, 13.12.
General procedure for synthesis of compounds (8a,b). A mixture of enamine 3b (0.30, 1 mmol) and 3-cyanomethylidene-2-oxindole derivatives 4a,b (1 mmol) was heated at reflux in anhydrous pyridine (5 mL) for 3 h. The excess pyridine was evaporated at reduced pressure and the residue was then treated with dil. HCl (1 N, 10 mL). The collected crude solid was crystallized from EtOH-dioxane (3:1, v/v).
ethyl 5-(2'-amino-3'-cyano-7',7'-dimethyl-2,5'-dioxo-5',6',7',8'-tetrahydro-1'H-spiro[indoline-3,4'-quinolin]-1'-yl)-3-phenyl-1H-pyrazole-4-carboxylate (8a): Yellow crystals (0.46 g, 83%), Mp 248-250 °C, IR (KBr): ν 3466, 3370, 3313, 3143 (2NH and NH2), 2188 (CN), 1705 (CO2CH2CH3), 1643 (br, 2CO) cm-1, 1H NMR (400 MHz, DMSO-d6): δ 0.87 (s, 3H, CH3), 0.94 (s, 3H, CH3), 1.11 (t, 3H, CO2CH2CH3), 1.87-2.29 (m, 4H, 2CH2), 4.20 (q, 2H, CO2CH2CH3), 5.73 (br s, 2H, NH2), 6.76-7.78 (m, 9H, ArH), 10.19 (br s, 1H, oxindole NH), 13.98 (br s, 1H, pyrazole NH) ppm; 13C NMR (100 MHz, CDCl3): δ 12.8 (CH3), 26.0 (CH3), 27.8 (CH3), 31.0 (C), 42.7 (CH2), 47.7 (C), 48.8 (CH2), 59.2 (CH2), 60.8 (C), 94.0 (C), 108.0 (C), 117.8 (CH), 120.6 (C), 122.6 (CH), 124.4 (C), 126.6 (CH), 126.9 (CH), 127.0 (C), 128.3 (CH), 128.4 (CH), 128.6 (C), 134.4 (C), 140.3 (C), 148.4 (C), 151.0 (C), 160.3 (C), 171.7 (C), 179.1 (C), 193.1 (C) ppm; MS (EI, 70 eV): m/z (%) 548 ([M+], 5), 505 (33), 464 (44), 418 (100), 384 (53), 287 (49), 104 (66), 77 (83), Anal. Calcd for C31H28N6O4: C, 67.87; H, 5.14; N, 15.32. Found: C, 67.79; H, 5.08; N, 15.36.
ethyl 5-(2'-amino-3'-cyano-1,7',7'-trimethyl-2,5'-dioxo-5',6',7',8'-tetrahydro-1'H-spiro[indoline-3,4'-quinolin]-1'-yl)-3-phenyl-1H-pyrazole-4-carboxylate (8b): Yellow crystals (0.46 g, 81%), Mp 248-250 °C, IR (KBr): ν 3394, 3226 (br, 2NH and NH2), 2184 (CN), 1701 (CO2CH2CH3), 1650, 1611 (2CO) cm-1, 1H NMR (400 MHz, DMSO-d6): δ 0.85 (s, 3H, CH3), 0.93 (s, 3H, CH3), 1.11 (t, 3H, CO2CH2CH3), 1.88-2.30 (m, 4H, 2CH2), 3.14 (s, 3H, NCH3), 4.20 (q, 2H, CO2CH2CH3), 5.79 (br s, 2H, NH2), 6.94-7.77 (m, 9H, ArH), 13.99 (br s, 1H, pyrazole NH) ppm, 13C NMR (100 MHz, CDCl3): δ 10.3 (CH3), 27.9 (2CH3), 32.3 (C), 41.8 (CH2), 50.0 (CH2), 99.2 (C), 112.0 (C), 125.9 (C), 128.1 (CH), 128.2 (CH), 132.0 (C), 138.2 (C), 152.9 (C), 161.9 (C), 196.9 (C) ppm, MS (EI, 70 eV): m/z (%) 562 ([M+], 22), 533 (13), 508 (25), 478 (85), 432 (100), 405 (32), 301 (21), 115 (33), 77 (57), Anal. Calcd for C32H30N6O4: C, 68.31; H, 5.37; N, 14.94. Found: C, 68.25; H, 5.33; N, 14.88.
General method for synthesis of compounds (12a,b). Compound 7a or 7b (1 mmol) was heated at reflux in acetic anhydride (5 mL) for 3 h. The excess solvent was removed at reduced pressure. The formed residue was extensively washed with aq. NaHCO3 (1 N, 10 mL). The collected precipitate was air-dried and crystallized from EtOH-dioxane (3:1, v/v).
1-Acetyl-2',5',11',11'-tetramethyl-2,9'-dioxo-1'-phenyl-9',10',11',12'-tetrahydrospiro[indoline-3,8'-pyrazolo[1',5':5,6][1,3,5]triazino[1,2-a]quinoline]-7'-carbonitrile (12a): Yellow crystals (0.43 g, 78%), Mp 248-250 °C, IR (KBr): ν 2113 (CN), 1754, 1739, 1660 (3CO) cm-1, 1H NMR (400 MHz, DMSO-d6): δ 0.23 (s, 3H, CH3), 0.84 (s, 3H, CH3), 1.82 (m, 2H, CH2), 2.08 (m, 2H, CH2), 2.22 (s, 3H, COCH3), 2.43 (s, 3H, pyrazole CH3), 2.60 (s, 3H, triazine CH3), 7.29-8.14 (m, 9H, ArH) ppm; 13C NMR (100 MHz, CDCl3): δ 13.9 (CH3), 23.3 (CH3), 24.8 (CH3), 26.5 (CH3), 28.4 (CH3), 32.5 (C), 40.4 (CH2), 49.5 (CH2), 51.4 (CH2), 94.0 (C), 112.4 (C), 113.5 (C), 116.8 (CH), 121.9 (C), 123.9 (CH), 125.8 (CH), 128.8 (CH), 129.1 (C), 129.5 (CH), 129.7 (CH), 130.2 (CH), 131.0 (C), 139.3 (C), 142.1 (C), 143.9 (C), 145.4 (C), 150.8 (C), 170.6 (C), 170.8 (C), 172.0 (C), 194.7 (C) ppm; MS (EI, 70 eV): m/z (%) 556 ([M+], 5), 513 (11), 446 (45), 129 (70), 83 (100), Anal. Calcd for C33H28N6O3: C, 71.21; H, 5.07; N, 15.10. Found: C, 71.17; H, 5.11; N, 15.21.
1,2',5',11',11'-Pentamethyl-2,9'-dioxo-1'-phenyl-9',10',11',12'-tetrahydrospiro[indoline-3,8'-pyrazolo[1',5':5,6][1,3,5]triazino[1,2-a]quinoline]-7'-carbonitrile (12b): Yellow crystals (0.40 g, 75%), Mp 248-250 °C, IR (KBr): ν 2121 (CN), 1767, 1725 (2CO) cm-1, 1H NMR (400 MHz, DMSO-d6): δ 0.22 (s, 3H, CH3), 0.83 (s, 3H, CH3), 1.77 (m, 2H, CH2), 2.06 (m, 2H, CH2), 2.40 (s, 3H, pyrazole CH3), 2.60 (s, 3H, triazine CH3), 3.18 (s, 3H, NCH3), 7.08-7.67 (m, 9H, ArH) ppm, MS (EI, 70 eV): m/z (%) 528 ([M+], 54), 524 (87), 267 (32), 252 (22), 239 (47), 211 (100), 194 (34), 115 (30), 77 (15), Anal. Calcd for C32H28N6O2: C, 72.71; H, 5.34; N, 15.90. Found: C, 72.63; H, 5.28; N, 15.81.

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