1H-Pyrazole-4-carboxylic acid, 5-amino-1-phenyl-, ethyl ester

white to light yellow crystalline flakes

Ethyl-2-cyano-3-ethoxyacrylate (1.5 g, 8.9 mmol. 1 eq.) was dissolved in ethanol (10 mL)withN, N. diisopropylethyiamine (0.74 mL, 9, 8 mmoi, 1.1 eq.) and phenylhydrazine (0.96 mL, 9.8 mmol, 1 .1 eq.) and the solution was heated to 85°C with stirring for 12 h. The reaction was condensed to dryness and dissolved in a minimal amount of dichioromethane and chrornatographed on silica gel (2O30percent ethyl acetate in hexane) to give ethy 5-amino-1-phenyl-1H-pyrazole-4-carboxylate (2) as an orange solid (2.0 g, 96percent yield). MS (EI) m/z 232 [M+H]Ethyl 5-amino-1-phenyl-1H-pyrazole-4-carboxylate (2a)Phenylhydrazine (1 equivalent) in ethanol was added drop wise to ethanolic solution of ethylehoxymethylene cyanoacetate (1 equivalent). The reaction was refluxed at 70 C for 6-7 hours. The reaction mixture was poured in ice cold water and stirred for 15-20 min when a precipitate separates out. The precipitate formed was filtered off and dried. Yield: 90percent; Melting point: 92°C; LC-ESI-MS (m/z): 232.2 (M+1).A mixture of ethyl 2-cyano-3-ethoxyacrylate (3.00 g, 17.7 mmol) and phenyl hydrazine (1.75 mL, 17.7 mmol) in ethanol (75 mL) was stirred at 0 °C for 1h. Then, the mixture was stirred at 80 °C for 5 h. After cooling the reaction mixture to room temperature, ethanol was removed in vacuo and the residue was partitioned between ethyl acetate and water. The organic layer was dried over magnesium sulfate. The solvent was evaporated in vacuo and the residue was chromatographed on a silica gel column with a mixture of n-hexane and ethyl acetate (6:1) to give the desired product 2a (3.71 g, 90 percent). A mixture of phenylhydrazine (9 mmol) and 10 mL of ethanolwas stirred and allowed to reflux for 1 h. Then, ethyl(ethoxymethylene)cyanoacetate (9 mmol) dissolved in 10 mL ofethanol was slowly added. The reaction mixture was refluxed for20 min. The reaction mixture was poured into 50 mL of ice-coldwater. The precipitate was collected by filtration and washed withwater to afford 13 in 70percent yield.Yield: 70percent. Mp: 98 C. IR (KBr. cm1): 3400–3140; 2995; 2912;1677; 1621; 1552; 1528; 1280; 781–697. 1H NMR (400 MHz, CDCl3, TMS, d in ppm): 1.36 (t, 3H, J = 7.1 Hz; CH2CH3); 4.30 (q, 2H, J = 7.1 Hz CH2CH3); 5.31 (s, 2H, NH2); 7.41–7.37 (m, 1H, H40);7.55–7.48 (m, 4H, H20, H30, H50, H60); 7.78 (s, 1H, H3). 13C NMR(100 MHz, CDCl3, TMS, d in ppm): 14.5; 59.6; 96.2; 123.8; 128.1;129.7; 137.6; 140.6; 149.0; 164.6. EI [M1] 230.2.Example 79; Preparation of (3-chloro-4-methoxy-phenyl)-(1, 6-diphenyl-1H-pyrazolo[3, 4-d]pyrimidin-4-yl)-amine hydrochloride (E 79) Step 1: Preparation of 5-amino-3-methyl-1-phenyl-1H-pyrazole-4-carboxylic acid ethyl ester (20) To a solution of compound 20 (7 grams, 41.4 mmol) in ethanol (70 mL) was added phenyl hydrazine (4.4 grams, 41.4 mmol) and the resulting reaction mixture was refluxed for 24 hours under nitrogen atmosphere. Then mixture was cooled to room temperature and concentrated under reduced pressure to afford the title compound 5-(4-fluoro-benzoylamino)-1-phenyl-1H-pyrazole-4-carboxylicacid ethyl ester (21) 8 grams as an off white solid. Yield: 84percent; [Preparation Example 1] Preparation of compound 1 [75] [76] [77] Preparation of compound 1-1 [78] Phenylhydrazine (40 g, 0.36 mol), (E)-ethyl 2-cyano-3-ethoxyacrylate (62 g, 0.36 mol), and EtOH (400 mL) were added and the mixture was stirred for 2 hours at 100 °C. Upon completion of the reaction, a compound 1-1 (70g, 82percent) was given through purification by column chromatography after removing EtOH by a rotary evaporator.General procedure: After standard evacuation and back-fill cycles with argon, a Schlenk tube fitted with a magnetic stirrer bar was charged with pyrazole derivative (1.29 mmol), aryl iodide (1.1 eq), K

Molecular Weight:231.25
XLogP3:2.3
Hydrogen Bond Donor Count:1
Hydrogen Bond Acceptor Count:4
Rotatable Bond Count:4
Exact Mass:231.100776666
Monoisotopic Mass:231.100776666
Topological Polar Surface Area:70.1
Heavy Atom Count:17
Complexity:267
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes