Multi-component solvent-free versus stepwise solvent mediated reactions: Regiospecific formation of 6-trifluoromethyl and 4-trifluoromethyl-1H-pyrazolo[3,4-b]pyridines (original) (raw)

Abstract

Multicomponent reactions (MCRs) are special type of synthetically useful organic reactions, in which three or more simple reactants are consumed in a single chemical step to produce a product that incorporates substantial portions of all the reactants. Generally multicomponent reactions, being one-pot process, afford good yields. They are fundamentally different from two component stepwise reactions in several ways such as: the simplicity of one-pot procedure, possible structural variation, complicated synthesis and large number of accessible compounds. Organic reactions under solvent-free conditions have gained much attention due to several advantages over the conventional methods in terms of enhanced selectivity, cleaner reaction profile, ease of manipulation and relatively benign conditions [1-6]. Among the condensed heterocyclic systems, pyrazolo[3,4b]pyridines are an important class of heterocyclic systems being part of therapeutically interesting compounds that display significant activity such as antimicrobial [7], antiviral [8], antiinflammatory [9], antitumor agents [10] and as potent PDE4B inhibitors [11]. In addition, pyrazolo[3,4-b]pyridines with a trifluoromethyl group are known to possess multidrug function with antimalarial activity [12]. The foregoing observations prompted us to undertake the preparation of trifluoromethyl substituted pyrazolo[3,4-b]pyridines. Generally, the synthesis of such heterocycles is accomplished by two distinct routes. The first one (Route A, Fig. 1) involves formation of a pyrazole ring on a 3acetyl/cyanopyridine bearing a good leaving group in 2-position, but this method lacks versatility in terms of substitution, as only pyridines containing, methyl, aryl, hydroxyl and amino groups at position-3 can be attained. The second route uses the condensation reaction of 5-amino-1H-pyrazoles with bifunctional electrophiles to form the pyridine moiety (Route B, Fig. 1), and offers a great diversity and flexibility in terms of substitution at pyrazole and pyridine rings. Nevertheless, this method is disadvantageous due to multiple step synthesis, large reaction times and low/moderate yields. Moreover, formation of different regioisomers has been reported in the literature i.e. in the reaction of 5-amino-1H-pyrazoles with trifluoromethyl-b-diketones under similar reaction conditions [13,14]. In view of these observations and our ongoing interest to develop greener protocols for the synthesis of heterocyclic compounds [15-18], we report here a mild and efficient MCR providing a regiospecific synthesis of 6-trifluoromethyl-1Hpyrazolo[3,4-b]pyridines under solvent-free conditions. At the same time, and in order to compare the results obtained by MCR with those using a multistep solvent mediated process, regioisomeric 4-trifluoromethyl-1H-pyrazolo[3,4-b]pyridines will also be described.

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References (96)

  1. H, 2.78; N, 11.05. Found: C, 61.58; H, 2.75; N, 11.02. 1-(Benzothiazol-2 0 -yl)-4-phenyl-3-(p-tolyl)-6-trifluoromethyl- 1H-pyrazolo[3,4-b]pyridine 4e: Mp 200 8C; IR (KBr, cm À1 ): 1528, 3063(-C5 5N);
  2. H NMR (300 MHz, CDCl 3 ) d: 2.33 (s, 3H, 4 00 -CH 3 ),
  3. C NMR (75 MHz, CDCl 3 ) d: 21.36 (4 00 -CH 3 ), 115.80, 116.77, 121.41 (q, 1 J C-F = 273 Hz), 122.67, 125.20, 126.22, 126.54, 126.90, 128.35, 128.46, 128.73, 129.43, 129.65, 132.60, 139.17, 135.20, 147.46 (q, 2 J C-F = 35 Hz), 148.43, 149.59, 150.37, 150.53, 156.18;
  4. F NMR (282 MHz, CDCl 3 ) d: À66.59 (6-CF 3 );
  5. MS (EI) m/z: 487 [M+1] + ; Elemental analysis calcd. for C 27 H 17 F 3 N 4 S: C, 66.66; H, 3.52; N, 11.52. Found: C, 66.62;
  6. H, 3.48; N, 11.48.
  7. -(Benzothiazol-2 0 -yl)-4-(2 000 -thienyl)-3-(p-tolyl)-6-trifluoro- methyl-1H-pyrazolo[3,4-b]pyridine 4f: Mp 210 8C; IR (KBr, cm À1 ): 1528, 3063 (-C5 5N);
  8. H NMR (300 MHz, CDCl 3 ) d: 2.48 (s, 3H, 4 00 - CH 3 ), 6.82 (m, 1H, C 4 H 3 S), 7.11 (m, 1H, C 4 H 3 S), 7.32-7.65 (m, 7H, C 6 H 4 , C 4 H 3 S, 5 0 , 6 0 -H), 7.77 (s, 1H, 5-H), 7.96 (d, 1H, 7 0 -H, J = 7.8), 8.18 (d, 1H, 4 0 -H, J = 8.1 Hz);
  9. C NMR (75 MHz, CDCl 3 ) d: 21.34 (4 00 -CH 3 ), 115.75, 117.14, 121.24, 121.34 (q, 1 J C-F = 273 Hz), 122.37, 125.57, 126.43, 127.54, 128.56, 128.73, 129.02, 129.22, 129.43, 132.22, 135.39, 135.80, 147.52 (q, 2 J C-F = 35 Hz), 147.76, 148.14, 150.13, 150.44, 156.24;
  10. F NMR (282 MHz, CDCl 3 ) d: À66.67 (6-CF 3 );
  11. MS (EI) m/z: 493 [M+1] + ; Elemental analysis calcd. for C 25 H 15 F 3 N 4 S 2 : C, 60.96;
  12. H, 3.07; N, 11.38. Found: C, 60.92; H, 3.02; N, 11.34. 1-(6 0 -Fluorobenzothiazol-2 0 -yl)-4-methyl-3-(p-tolyl)-6-trifluoro- methyl-1H-pyrazolo[3,4-b]pyridine 4g: Mp 236 8C; IR (KBr, cm À1 ): 1535, 3063 (-C5 5N);
  13. H NMR (300 MHz, CDCl 3 ) d: 2.49 (s, 3H, 4 00 - CH 3 ), 2.60 (s. 3H, 4-CH 3 ), 7.34-7.37 (m, 3H, C 6 H 4 , 5 0 -H), 7.53 (s, 1H, 5-H), 7.60-7.63 (m, 3H, C 6 H 4 ,7 0 -H), 8.05-8.10 (m, 1H, 4 0 -H);
  14. C NMR (75 MHz, CDCl 3 ) d: 20.16 (4-CH 3 ), 21.36 (4 00 -CH 3 ), 115.60, 116.40, 118.76 (q, 1 J C-F = 273 Hz), 122.10, 123.14, 126.55 (d, 2 J C- F = 24 Hz), 128.16, 129.06, 129.87, 132.63, 135.34, 147.56 (q, 2 J C- F = 35 Hz), 147.92, 148.39, 150.21, 150.31, 155.99, 157.16;
  15. F NMR (282 MHz, CDCl 3 ) d: À66.78 (6-CF 3 ), À116.16 (6 0 -F);
  16. MS (EI) m/z: 443 [M+1] + ; Elemental analysis calcd. for C 22 H 14 F 4 N 4 S: C, 59.72; H, 3.19;
  17. -(6 0 -Fluorobenzothiazol-2-yl)-4-phenyl-3-(p-tolyl)-6-trifluoro- methyl-1H-pyrazolo[3,4-b]pyridine 4h: Mp 218 8C; IR (KBr, cm À1 ): 1528, 3078 (-C5 5N);
  18. H NMR (300 MHz, CDCl 3 ) d: 2.33 (s, 3H, 4 00 - CH 3 ), 6.95 (d, 2H, C 6 H 4 ,J = 7.8 Hz), 7.16 (d, 2H, C 6 H 4 , J = 7.8 Hz),
  19. C NMR (75 MHz, CDCl 3 ) d: 21.35 (4 00 -CH 3 ), 115.74, 116.72, 121.42 (q, 1 J C-F = 273 Hz), 122.57, 123.16, 126.18 (d, 2 J C-F = 24 Hz), 126.56, 126.98, 128.13,128.76, 129.56, 129.86, 129.88, 132.77, 135.16, 147.68 (q, 2 J C-F = 35 Hz), 147.82, 148.34, 150.34, 150.47, 156.11, 157.28;
  20. F-NMR (282 MHz, CDCl 3 ) d: À66.66 (6-CF 3 ), À116.03 (6 0 -F); MS (EI) m/z: 505 [M+1] + ; Elemental analysis calcd. for C 27 H 16 F 4 N 4 S: C, 64.28; H, 3.20; N, 11.11. Found: C, 64.24; H, 3.16; N, 11.06.
  21. 2. General procedure for the synthesis of 3-phenyl-1-(benzothiazol- 2 0 -yl)-5-aminopyrazole 5a A mixture of 2-hydrazinobenzothiazole 1a (0.825 g, 5 mmol) and a-cyanoacetophenone 2a (0.73 g, 5 mmol) was refluxed in ethanol containing acetic acid (3ml) for 5-6 h. Excess solvent was removed by distillation. The crude product so obtained was recrystallized from ethanol to give 5a (1.09 g, 75%), Mp 201 8C (lit.
  22. 202 8C). Other compounds (5b-d) of this type were prepared similarly. 5-amino-1-(benzothiazol-2 0 -yl)-3-phenyl-1-H-pyrazole 5a: Mp 200 8C (lit. [20] 202 8C).
  23. -amino-1-(benzothiazol-2 0 -yl)-3-(p-chlorophenyl)-1-H-pyrazole 5b: Mp 226 8C (lit. [20] 227 8C).
  24. -amino-1-(benzothiazol-2 0 -yl)-3-(p-tolyl)-1-H-pyrazole 5c: Mp 2278C (lit. [20] 228 8C).
  25. -amino-1-(6 0 -fluorobenzothiazol-2 0 -yl)-3-(p-tolyl)-1-H-pyrazole 5d: Mp 213 8C; IR (KBr, cm À1 ): 3201, 3317 (NH);
  26. H NMR (300 MHz, CDCl 3 ) d: 2.42 (3H, s, 4 00 -CH 3 ), 7.24-7.84 (m, 8H, C 6 H 4 , 4 0 , 5 0 , 7 0 , 4-H);
  27. MS (EI) m/z: 325 [M+1] + ; Elemental analysis calcd. for C 17 H 13 FN 4 S: C, 62.95; H, 4.04; N, 17.27. Found: C, 62.91; H, 4.01; N, 17.24.
  28. 3. General procedure for synthesis of 1-(benzothiazole-2 0 -yl)-3- aryl-6-substituted-4-trifluoromethyl-1H-pyrazolo[3,4-b]pyridines 6a-h and 5-acetylamino-1-(benzothiazol-2 0 -yl)-3-substituted-1-H- pyrazoles 7a-d 3-aryl-1-(benzothiazol-2 0 -yl)-5-aminopyrazole 5 (5 mmol) was dissolved in acetic acid (20 ml) and equimolar amount of appropriate trifluoromethyl-b-diketones 3 was added to it. The reaction mixture was heated to reflux at about 10 h. After completion of reaction, the reaction mixture was poured in excess of water and filtered. The crude products thus obtained were separated by column chromatography using silica gel (100-200 mesh) with petroleum ether/ethyl acetate (99.5/0.5) as an eluent afforded 6 and further elution of column with petroleum ether/ ethyl acetate (99: 1) furnished 7. 1-(Benzothiazol-2 0 -yl)-6-methyl-3-phenyl-4-trifluoromethyl-1H- pyrazolo[3,4-b]pyridine 6a: Mp 256 8C; IR (KBr, cm À1 ): 1528, 3078 (-C5 5N);
  29. H NMR (400 MHz, CDCl 3 ) d: 2.93 (s, 3H, 6-CH 3 ), 7.39 (t, 1H, 6 0 -H) 7.42-7.50 (m, 5H, Hm, Hp, 5 0 , 5-H), 7.62 (m, 2H, Ho), 7.89 (dd, 1H, 7 0 -H, J = 8.0, 0.5 Hz), 8.11 (td, 1H, 4 0 -H, J = 8.2, 0.4 Hz);
  30. C NMR (75 MHz, CDCl 3 ) d: 25.15 (6-CH 3 ), 110.0, 116.68 (q, 3 J C- F = 5.2 Hz), 121.12, 122.0 (q, 1 J C-F = 273.
  31. 9 Hz), 123.21, 124.87, 126.45, 127.89, 129.33, 129.76, 131.68, 132.86 (q, 2 J C-F = 35.1 Hz), 133.17, 148.46, 150.15, 151.40, 156.47, 161.22;
  32. F NMR (282 MHz, CDCl 3 ) d: À60.04 (4-CF 3 );
  33. MS (EI) m/z: 411 [M+1] + ; Elemental analysis calcd. for C 21 H 13 F 3 N 4 S: C, 61.46; H, 3.19; N, 13.65. Found: C, 61.38; H, 3.16; N, 13.62.1-(Benzothiazol-2 0 -yl)-3- phenyl-4,6-bistrifluoromethyl-1H-pyrazolo[3,4-b]pyridine 6b: Char- acterisation data of 6b is similar to that of 4b.
  34. -(Benzothiazol-2 0 -yl)-3-(p-chlorophenyl)-6-methyl-4-trifluoro- methyl-1H-pyrazolo[3,4-b]pyridine 6c: Mp 198 8C; IR (KBr, cm À1 ): 1528, 3078 (-C5 5N);
  35. H NMR (300 MHz, CDCl 3 ) d: 2.96 (s, 3H, 6-CH 3 ),
  36. C NMR (75 MHz, CDCl 3 ) d: 25.12 (6- CH 3 ), 95.19, 116.77, 121.15, 122.01 (q, 1 J C-F = 272 Hz), 123.21, 124.99, 126.54, 127.47, 128.86, 129.06, 130.15, 132.69 (q, 2 J C- F = 35 Hz), 133.20, 147.25, 150.24, 151.46, 156.76, 161.45;
  37. F NMR (282 MHz, CDCl 3 ) d: À59.77 (4-CF 3 );
  38. MS (EI) m/z: 445/447 (3:1)
  39. H, 2.72; N, 12.59. Found: C, 56.67; H, 2.70; N, 12.56.
  40. -(Benzothiazol-2 0 -yl)-3-(p-chlorophenyl)-6-phenyl-4-trifluoro- methyl-1H-pyrazolo[3,4-b]pyridine 6d: Mp 224 8C; IR (KBr, cm À1 ): 1535, 3047(-C5 5N);
  41. H NMR (300 MHz, CDCl 3 ) d: 7.46-7.66 (m, 8H, C 6 H 4 , C 6 H 5 , 6 0 -H), 8.01 (m, 1H, 5 0 -H) 8.15 (d, 1H, 7 0 -H, J = 8.4 Hz)
  42. 18 (s, 1H, 5-H), 8.36 (m, 1H, 4 0 -H), 8.48 (d, 2H, C 6 H 4 , J = 6.9 Hz);
  43. C NMR (75 MHz, CDCl 3) d: 110.17, 115.56, 121.27, 121.84 (q, 1 J C- F = 272 Hz), 121.36, 123.24, 124.33, 126.68, 126.66, 128.29, 128.33, 129.55, 131.03, 132.38 (q, 2 J C-F = 36 Hz), 132.46, 136.37, 138.22, 146.38, 148.41, 150.91, 154.76, 158.36;
  44. F NMR (282 MHz, CDCl 3 ) d: À59.88 (4-CF 3 );
  45. MS (EI) m/z: 507/509 (3:1) [M+1] + /[M+1+2] + ; Elemental analysis calcd. for C 26 H 14 ClF 3 N 4 S: C, 61.60; H, 2.78; N, 11.05. Found: C, 61.58; H, 2.75; N, 11.02.
  46. H NMR (300 MHz, CDCl 3 ) d: 2.48 (s, 3H, 4 00 -CH 3 ),
  47. C NMR (75 MHz, CDCl 3 ) d: 21.49 (4 00 -CH 3 ), 110.59, 113.19, 123.04 (q, 1 J C-F = 275 Hz), 123.16, 126.12, 126.56, 127.93, 127.97, 128.07, 128.62, 129.30, 129.69, 131.03, 133.32, 133.77 (q, 2
  48. J C-F = 35 Hz), 136.94, 139.30, 148.94, 149.78, 151.65, 155.37, 158.36;
  49. F NMR (282 MHz, CDCl 3 ) d: À59.81 (4-CF 3 );
  50. MS (EI) m/z: 487 [M+1] + ; Elemental analysis calcd. for C 27 H 17 F 3 N 4 S: C, 66.66; H, 3.52;
  51. -(Benzothiazol-2 0 -yl)-6-(2 00 -thienyl)-3-(p-tolyl)-4-trifluoro- methyl-1H-pyrazolo[3,4-b]pyridine 6f: Mp 227 8C; IR (KBr, cm À1 ): 1535, 3063 (-C5 5N);
  52. H NMR (300 MHz, CDCl 3 ) d: 2.48 (s, 3H, 4 00 - CH 3 ), 7.25-7.67 (m, 8H, C 6 H 4 , C 4 H 3 S, 5 0 , 6 0 -H), 7.95 (m, 2H, C 4 H 3 S,
  53. C NMR (75 MHz, CDCl 3 ) d: 21.48 (4 00 -CH 3 ), 109.25, 112.47, 121.07 (q,
  54. J C-F = 274 Hz), 121.22, 123.14, 123.87, 126.54, 127.68, 128.24, 128.78, 129.13, 129.68, 130.90, 133.36 (q, 2 J C-F = 36 Hz), 133.47, 136.20, 139.29,142.82, 149.73, 150.29, 153.23, 158.16;
  55. F NMR (282 MHz, CDCl 3 ) d: À60.01 (4-CF 3 );
  56. MS (EI) m/z: 493 [M+1] + ; Elemental analysis calcd. for C 25 H 15 F 3 N 4 S 2 : C, 60.96; H, 3.07; N, 11.38. Found: C, 60.92; H, 3.02; N, 11.34.
  57. -(6 0 -Fluorobenzothiazol-2 0 -yl)-6-methyl-3-(p-tolyl)-4-trifluoro- methyl-1H-pyrazolo[3,4-b]pyridine 6g: Mp 208 8C; IR (KBr, cm À1 ): 1531, 3068 (-C5 5N);
  58. H NMR (300 MHz, CDCl 3 ) d: 2.47 (s, 3H, 4 00 - CH 3 ), 2.95 (s, 3H, 6-CH 3 ), 7.21-7.52 (m, 5H, C 6 H 4 , 5-H), 7.58 (m, 1H, 5 0 -H, J = 8.1 Hz), 7.82 (d, 1H, 7 0 -H, J = 7.8 Hz), 8.16 (dd, 1H, 4 0 -H, J = 4.8, 9.0, 9.0 Hz);
  59. C NMR (75 MHz, CDCl 3 ) d: 21.46 (4 00 -CH 3 ), 25.13(6-CH 3 ), 107.70, 114.76, 120.27 (q, 1 J C-F = 274 Hz), 122.65, 124.09, 124.21, 126.18 (d, 2 J C-F = 24 Hz), 128.64, 129.40, 129.58, 134.21 (q, 2 J C-F = 36 Hz), 146.79, 139.34, 149.14, 151.39, 154.39, 157.70, 161.26;
  60. F NMR (282 MHz, CDCl 3 ) d: À59.99 (4-CF 3 ), À116.06 (6 0 -F);
  61. MS (EI) m/z: 443 [M+1] + ; Elemental analysis calcd. for C 22 H 14 F 4 N 4 S: C, 59.72; H, 3.19; N, 12.66. Found: C, 59.68; H, 3.15; N, 12.64.
  62. -(6 0 -Fluorobenzothiazol-2-yl)-6-phenyl-3-(p-tolyl)-4-trifluoro- methyl-1H-pyrazolo[3,4-b]pyridine 6h: Mp 241 8C; IR (KBr, cm À1 ): 1543, 3070 (-C5 5N);
  63. H NMR (300 MHz, CDCl 3 ) d: 2.48 (s, 3H, 4 00 - CH 3 ), 7.30-7.66 (m, 9H, C 6 H 4 , Ph, 7 0 , 5 0 -H), 8.07 (d, 1H, 4 0 -H, J = 5.1 Hz), 8.12 (s, 1H, 5-H), 8.36 (d, 2H, J = 6.
  64. C NMR (75 MHz, CDCl 3 ) d: 21.49 (4 00 -CH 3 ), 107.41, 111.19 (q, 1 J C- F = 271 Hz), 113.34, 123.91, 124.02, 124.14, 127.90 (d, 2 J C- F = 24 Hz), 128.64, 129.33, 129.65, 131.10, 133.84 (q, 2 J C- F = 35 Hz), 134.23, 134.37, 136.84, 139.38, 146.28, 149.06, 151.57, 154.88, 158.53, 161.78;
  65. F NMR (282 MHz, CDCl 3 ) d: À60.03 (4-CF 3 ), À116.09 (6 0 -F);
  66. MS (EI) m/z: 505 [M+1] + ; Elemental analysis calcd. for C 27 H 16 F 4 N 4 S: C, 64.28; H, 3.20; N, 11.11. Found: C, 64.24; H, 3.16; N, 11.06. 5-acetylamino-1-(benzothiazol-2 0 -yl)-3-phenyl-1H-pyrazole 7a: Mp 191 8C (lit. [20] 192 8C).
  67. -acetylamino-1-(benzothiazol-2 0 -yl)-3-(p-chlorophenyl)-1H- pyrazole 7b: Mp 206 8C (lit. [20] 208 8C).
  68. -acetylamino-1-(benzothiazol-2 0 -yl)-3-(p-tolyl)-1H-pyrazole 7c: Mp 238 8C (lit. [20] 240 8C).
  69. -acetylamino-1-(6 0 -fluorobenzothiazol-2 0 -yl)-3-(p-tolyl)-1H- pyrazole 7d: Mp 190 8C; IR (KBr, cm À1 ): 3200 (NH),1698 (CO);
  70. H NMR (300 MHz, CDCl 3 ) d: 2.38 (3H, s, COCH 3 ), 2.42 (3H, s, 4 00 -CH 3 ),
  71. V.A. Chebanov, Y.I. Sakhno, S.M. Desenko, V.N. Chernenko, V.I. Musatov, S.V. Shishkina, O.V. Shishkin, C.O. Kappe, Tetrahedron 63 (2007) 1229-1242.
  72. S. Sharma, S. Gangal, A. Rauf, Rasayan J. Chem. 4 (2008) 693-717.
  73. S. Song, L. Song, B. Dai, H. Yi, G. Jin, S. Zhu, M. Shao, Tetrahedron 64 (2008) 5728- 5735.
  74. P. Wang, L. Song, H. Yi, M. Zhang, S. Zhu, H. Deng, M. Shao, Tetrahedron Lett. 51 (2010) 3975-3977.
  75. H. Yi, L. Song, W. Wang, J. Liu, S. Zhu, H. Deng, M. Shao, Chem. Commun. 46 (2010) 6941-6943.
  76. B. Dai, Y. Duan, X. Liu, L. Song, M. Zhang, W. Cao, S. Zhu, H. Deng, M. Shao, J. Fluorine Chem. 133 (2012) 127-133.
  77. H. Mello, A. Echevarria, A.M. Bernardino, M. Canto-Cavalheiro, L.L. Leon, J. Med. Chem. 47 (2004) 5427-5432;
  78. I. Sekikawa, J. Nishie, S. Tono-oka, Y. Tanaka, S. Kakimoto, J. Heterocycl. Chem. 10 (1973) 931-932.
  79. T.J. Tucker, J.T. Sisko, R.M. Tynebor, T.M. Williams, P.J. Felock, A.J. Flynn, M.T. Lai, Y. Liang, G. McGaughey, M. Liu, M. Miller, G. Moyer, V. Munshi, R. Perlow-Poehnelt, S. Prasad, J.C. Reid, R. Sanchez, M. Torrent, J.P. Vacca, B.L. Wan, Y. Yan, J. Med. Chem. 51 (2008) 6503-6511.
  80. H. Ochiai, A. Ishida, T. Ohtani, K. Kusumi, K. Kishikawa, S. Yamamoto, H. Takeda, T. Obata, H. Makai, M. Toda, Bioorg. Med. Chem. 12 (2004) 4089-4100;
  81. L. Revesz, E. Blum, F.E. Di Padova, T. Buhl, R. Feifel, H. Gram, P. Hiestand, U. Manning, U. Neumann, G. Rucklin, Bioorg. Med. Chem. Lett. 16 (2006) 262-266.
  82. R. Lin, P.J. Connolly, Y. Lu, G. Chiu, S. Li, Y. Yu, S. Huang, X. Li, S.L. Emanuel, S.A. Middleton, R.H. Gruninger, M. Adams, A.R. Fuentes-Pesquera, L.M. Greenberger, Bioorg. Med. Chem. Lett. 17 (2007) 4297-4302.
  83. C.J. Mitchell, S.P. Ballantine, D.M. Coe, C.M. Cook, C.J. Delves, M.D. Dowle, C.D. Edlin, J.N. Hamblin, S. Holman, M.R. Johnson, P.S. Jones, S.E. Keeling, M. Kranz, M. Lindvall, F.S. Lucas, M. Neu, Y.E. Solanke, D.O. Somers, N.A. Trivedi, J.O. Wiseman, Bioorg. Med. Chem. Lett. 20 (2010) 5803-5806.
  84. R.S. Dias, A.C. Freitas, E.J. Barreiro, D.K. Goins, D. Nanayakkara, J.D. Mcchesney, Bull. Chim. Farm 139 (2000) 14-20.
  85. S.P. Singh, R. Naithaini, R. Aggarwal, O. Parkash, Synth. Commun. 34 (2004) 4359- 4367.
  86. E.E. Emelina, A.A. Petrov, S.I. Selivanov, D.V. Filyukov, Russ. J. Org. Chem. 44 (2008) 251-256.
  87. R. Aggarwal, G. Sumran, Synth. Commun. 36 (2006) 1873-1878.
  88. R. Aggarwal, G. Sumran, A. Saini, S.P. Singh, Tetrahedron Lett. 47 (2006) 4969- 4971.
  89. R. Aggarwal, G. Sumran, Synth. Commun. 36 (2006) 875-879.
  90. R. Aggarwal, R. Kumar, V. Kumar, J. Sulphur Chem. 28 (2007) 617-623.
  91. D. Numann, G. Gilkes, J. Kischkewitz, J. Fluorine Chem. 30 (1985) 73-87.
  92. S.P. Singh, O. Prakash, R.K. Tomer, S.N. Sawhney, Indian J. Chem. 16B (1978) 733- 734.
  93. S.P. Singh, J.K. Kapoor, D. Kumar, M.D. Threadgill, J. Fluorine Chem. 83 (1997) 73.
  94. M.J. Uddin, P.N.P. Rao, E.E. Knaus, Bioorg. Med. Chem. 11 (2003) 5273-5280.
  95. H.K. Gakhar, G.S. Gill, J.S. Multani, J. Indian Chem. Soc. 48 (1971) 953.
  96. L. Katz, J. Am. Chem. Soc. 73 (1951) 4007-4010.