ACCEPTED MANUSCRIPT
TLC. The crude was purified by chromatography on Silica gel using diethyl ether as eluent or
recrystallized from absolute ethanol.
4.1.9.1 Ethyl 2-phenyl-1-((3-(trifluoromethyl)phenyl)carbamoyl)-2,3-dihydro-1H-imidazo[1,2-
1
b]pyrazole-7-carboxylate 17. White solid. Yield: 36%; mp: 153–154 °C. H-NMR (CDCl3): δ 1.42
(t, J = 5.4, 3H, CH3), 4.20 (near t, 1H, H3), 4.42 (q, J = 5.4, 2H, CH2), 4.81 (near t, 1H, H2), 6.50
(near t, 1H, H3), 7.20–7.80 (m, 9H, Ar), 7.91 (s, 1H, H6), 11.60 (s, 1H, NH, disappears with D2O).
IR (CHCl3): cm-1 3214 (NH), 1710–1690 (COOEt + CONH). Anal. (C22H19F3N4O3) calcd for C, H,
N.
4.1.9.2
2-Phenyl-N1-(3-(trifluoromethyl)phenyl)-2,3-dihydro-1H-imidazo[1,2-b]pyrazole-1,7-
dicarboxamide 18. White solid. Yield: 28%; mp: 226–227 °C. 1H-NMR (DMSO-d6): δ 3.72 (near t,
1H, H3), 4.58 (near t, 1H, H2), 5.40 (near t, 1H, H3), 7.05–7.42 (m, 10H, 9Ar + NH, 1H disappears
with D2O), 7.62 (s,1H, H6). IR (KBr): cm-1 3450, 3223, 2871 (NH2 + NH), 1666 (CONH2), 1609
(CONH). Anal. (C20H16F3N5O2) calcd for C, H, N.
4.1.9.3
2-Phenyl-7-(piperidine-1-carbonyl)-N-(3-(trifluoromethyl)phenyl)-2,3-dihydro-1H-
1
imidazo[1,2-b]pyrazole-1-carboxamide 19. White solid. Yield: 50%; mp: 159–160 °C. H-NMR
(CDCl3): δ 1.45–1.80 (m, 6H, 3CH2-pip), 3.71–3.93 (m, 4H, 2CH2N-pip), 4.18 (near t, 1H, H3),
4.78 (near t, 1H, H2), 6.35 (near t, 1H, H3), 7.20–7.55 (m, 9H, Ar), 7.90 (s, 1H, H6), 10.90 (s, 1H,
NH, disappears with D2O). IR (CHCl3): cm-1 3020 (NH), 1692 (CONH), 1576 (CON-pip). Anal.
(C25H24F3N5O2) calcd for C, H, N.
4.1.10 Synthesis of ethyl 2-phenyl-2,3-dihydro-1H-imidazo[1,2-b]pyrazole-6-carboxylate 40.
Ethyl 5-amino-1-(2-hydroxy-2-phenylethyl)-1H-pyrazole-3-carboxylate (32) (0.27 g, 1 mmol) was
dissolved in concentrated sulfuric acid (2 mL) at 0 °C and the mixture was stored at room
temperature for 15 min. Then, ice-water (50 mL) was added and the solution was made neutral with
NH4OH solution. The yellow solid obtained was filtered, washed with water and recrystallized from
1
95% ethanol. White solid. Yield: 80%; mp 128–129 °C. H-NMR (CDCl3): δ 1.41 (t, J = 7.2, 3H,
CH3), 4.03 (near t, 1H, H3), 4.40 (q, J = 7.2, 2H, CH2O), 4.61 (near t, 1H, H2), 4.79 (br s, 1H, NH,
disappears with D2O), 5.38 (near t, 1H, H3), 5.98 (s, 1H, H7), 7.27–7.52 (m, 5H, Ar).
IR (KBr): cm-1 3350–3050 (NH), 1720 (CO). Anal. (C14H15N3O2) calcd for C, H, N.
4.1.11 General procedure for the synthesis of ethyl 1-carbamoyl-2-phenyl-2,3-dihydro-1H-
imidazo[1,2-b]pyrazole-6-carboxylates 20–23.
A mixture of ethyl 2-phenyl-2,3-dihydro-1H-imidazo[1,2-b]pyrazole-6-carboxylate 40 (2.57 g, 10
mmol) and the suitable phenyl isocyanate (11 mmol) in an. DMF (30 mL) was refluxed for 18 h.
After cooling to room temperature the mixture was poured into ice-water (100 mL) and 1M HCl
solution was added until pH 5. The precipitated solid was filtered and dissolved in DCM (30 mL).