3-Amino-4-fluorobenzenemethanol

4-Fluoro-3-iodobenzylalcohol The product from Example 2A (7.0 g, 50 mmol) in water (100 mL) at 0° C. was treated slowly with concentrated sulfuric acid (30 mL) at a rate to maintain the temperature below 10° C. and then treated dropwise with an aqueous solution of sodium nitrite (3.45 g, 50 mmol). This solution was then added to a solution of potassium iodide (8.13 g, 50 mmol) in water (15 mL), heated to 60° C. for 2 hours, cooled and extracted with methylene chloride. The methylene chloride layer was washed with 10percent sodium hydroxide, washed with 1M sodium thiosulfate, washed with 10percent hydrochloric acid, washed with aqueous sodium bicarbonate, dried (sodium sulfate), filtered, and concentrated. The residue was purified by flash chromatography over silica gel (ethyl acetate/hexane 7:3) to provide 6.4 g of the title compound. 1H NMR (CDCl3) delta1.69 (t, 1H), 4.66 (d, 2H), 7.05 (t, 1H), 7.60 (d, 1H), 7.78 (dd, 1H).EXAMPLE 8B 4-Fluoro-3-iodobenzylalcohol The product from Example 8A (7.0 g, 50 mmol) in water (100 mL) at 0° C. was treated slowly with concentrated sulfuric acid (30 mL) at a rate to maintain the temperature below 10° C., then treated dropwise with an aqueous solution of sodium nitrite (3.45 g, 50 mmol). This solution was then added to a solution of potassium iodide (8.13 g, 50 mmol) in water (15 mL), heated to 60° C. for 2 hours, cooled, and extracted with methylene chloride. The organic phase was washed with 10percent sodium hydroxide, 1 M sodium thiosulfate, 10percent hydrochloric acid, aqueous sodium bicarbonate, dried (sodium sulfate), filtered, and the solvent evaporated. The crude product was purified by flash chromatography over silica gel (ethyl acetate/hexane 7:3) to provide 6.4 g of the title compound. 1H NMR (CDCl3) delta1.69 (t, 1H), 4.66 (d, 2H), 7.05 (t, 1H), 7.60 (d, 1H), 7.78 (dd, 1H).EXAMPLE 30B 4-Fluoro-3-iodobenzylalcohol The product from Example 30A (7.0 g, 50 mmol) in water (100 mL) at 0° C. was treated slowly with concentrated sulfuric acid (30 mL) at a rate to maintain the temperature below 10° C. and then treated dropwise with an aqueous solution of sodium nitrite (3.45 g, 50 mmol). This solution was then added to a solution of potassium iodide (8.13 g, 50 mmol) in water (15 mL), heated to 60° C. for 2 hours, cooled and extracted with methylene chloride. The methylene chloride layer was washed with 10percent sodium hydroxide, washed with 1M sodium thiosulfate, washed with 10percent hydrochloric acid, washed with aqueous sodium bicarbonate, dried (sodium sulfate), filtered, and concentrated. The residue was purified by flash chromatography over silica gel (ethyl acetate/hexane 7:3) to provide 6.4 g of the title compound. 1H NMR (CDCl3) delta 1.69 (t, 1H), 4.66 (d, 2H), 7.05 (t, 1H), 7.60 (d, 1H), 7.78 (dd, 1H).EXAMPLE 89B 4-fluoro-3-iodobenzylalcohol The product from Example 89A (7.0 g, 50 mmol) in water (100 mL) at 0 ° C. was treated slowly with concentrated sulfuric acid (30 mL) at a rate to maintain the temperature below 10 ° C., then treated dropwise with an aqueous solution of sodium nitrite (3.45 g, 50 mmol). This solution was then added to a solution of potassium iodide (8.13 g, 50 mmol) in water (15 mL), heated to 60 ° C. for 2 hours, cooled, extracted with methylene chloride, the organics washed with 10percent sodium hydroxide, 1M sodium thiosulfate, 10percent hydrochloric acid, aqueous sodium bicarbonate, dried (sodium sulfate), filtered and solvent evaporated. The material was purified by flash chromatography over silica gel (ethyl acetate/hexane 7:3) to provide 6.4 g of the title compound. 1H-NMR (CDCl3) delta 1.69 (t, 1H), 4.66 (d, 2H), 7.05 (t, 1H), 7.60 (d, 1H), 7.78 (dd, 1H).EXAMPLE 30B 4-Fluoro-3-iodobenzylalcohol The product from example 30A (7.0 g, 50 mmol) in water (100 mL) at 0° C. was treated slowly with concentrated sulfuric acid (30 mL) at a rate to maintain the temperature below 10° C. and then treated dropwise with an aqueous solution of sodium nitrite (3.45 g, 50 mmol). This solution was then added to a solution of potassium iodide (8.13 g, 50 mmol) in water (15 mL), heated to 60° C. for 2 hours, cooled and extracted with methylene chloride. The methylene chloride layer was washed with 10percent sodium hydroxide, washed with 1 M sodium thiosulfate, washed with 10percent hydrochloric acid, washed with aqueous sodium bicarbonate, dried (sodium sulfate), filtered, and concentrated. The residue was purified by flash chromatography over silica gel (ethyl acetate/hexane 7:3) to provide 6.4 g of the title compound. 1H NMR (CDCl3) delta 1.69 (t, 1H), 4.66 (d, 2H), 7.05 (t, 1H), 7.60 (d, 1H), 7.78 (dd, 1H).EXAMPLE 89B 4-Fluoro-3-iodobenzylalcohol The product from Example 89A (7.0 g, 50 mmol) in water (100 mL) at 0° C. was treated slowly with concentrated sulfuric acid (30 mL) at a rate to maintain the temperature below 10° C., then treated dropwise with an aqueous solution of sodium nitrite (3.45 g, 50 mmol). This solution was then added to a solution of potassium iodide (8.13 g, 50 mmol) in water (15 mL), heated to 60° C. for 2 hours, cooled, extracted with methylene chloride, the organics washed with 10percent sodium hydroxide, 1 M sodium thiosulfate, 10percent hydrochloric acid, aqueous sodium bicarbonate, dried (sodium sulfate), filtered and solvent evaporated. The material was purified by flash chromatography over silica gel (ethyl acetate/hexane 7:3) to provide 6.4 g of the title compound. 1H NMR (CDCl3) 1.69 (t, 1H), 4.66 (d, 2H), 7.05 (t, 1H), 7.60 (d, 1H), 7.78 (dd, 1H).Following literature procedure [3] a solution of 3-amino-4-fluorobenzoic acid (4.0 g, 26.3 mmol) in dry THF (20 ml) was treated with 1 M solution of BH3 in THF (53 mmol, 53 mL) at 0 °C. The reaction mixture was stirred at rt for 24 h, MeOH (10 mL) was slowly added, and stirred for 15 min, the solvents were evaporated, and the residue was purified on a silica gel plug (CH2Cl2/ EtOAc, 1:1) to give 3.47 g (94percent yield) of alcohol 9e as a white solid.Example 2A EXAMPLE 12A EXAMPLE 30A EXAMPLE 30A To a solution of I -(3-cyanophenyl)-3-(tri fluoromethyl)- I H -pyrazole-5-carboxylic acid (91) (5.67 g, 20.15 mrnol) in DMF (50 mL) was added (3-aniino-4- fluorophenyl)rnethanol (30b) (2.37 g, 16.79 mmol), N-ethyl-N-isopropylpropan-2-amine (14.62 mL, 84 mmol) and bromo-tris-pyrrolidinophosphoniumhexafluorophosphate(PyBrop) (8.61 g, 1 8.47 mmol) at room temperature. The resulting reaction mixture was stirred at room temperature for 16 h under nitrogen atmosphere. The reaction mixture diluted with water (25 mL) was extracted with ethyl acetate (2 x 50 niL), washed with brine (25 niL), the combined organic layer was dried over anhydrous MgSO4, filtered, and evaporated to dryness. The residue obtained was purifiedby flash column chromatography [silica gel 40 g, eluting with 0-100percent ethyl acetate/methanol (9/I) in hexanes] to furnish I -(3-cyanophenyl)-N-(2-fl uoro-5- (hydroxyrnethyl)phenyl)-3-(tri fluoromethyl)- I H-pyrazole-5-carboxamide (30c) (1 .66 g, 4.11 mmol, 24.45 percent yield) as a white solid; 'H NMR (300 MHz, DMSO-d, ) oe 10.57 (s, 1.H), 8.18'8.09 (m, lH), 8.00 (dt, J = 7.8, 1.3 Hz, 1K), 7.91 (ddd, J = 8.1, 2.3, 1.1 Hz, 1K), 7.78'7.69 (m, 2H), 7.57'7.45 (m, IH), 7.33'7.15 (ni, 2H), 5.30 (t, J = 5.7 Hz, 1K), 4.46(d, J 5.7 Hz, 2H); '9F NMR (282 MHz, DMSO-d6) oe -60.98, -124.32.; MS (ES+) 427.2(M+Na), (ES-) 403.2 (M-l).

Molecular Weight:141.14
XLogP3:0.5
Hydrogen Bond Donor Count:2
Hydrogen Bond Acceptor Count:3
Rotatable Bond Count:1
Exact Mass:141.058992041
Monoisotopic Mass:141.058992041
Topological Polar Surface Area:46.2
Heavy Atom Count:10
Complexity:110
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes