1-(2-BroMo-5-chlorophenyl)-3-Methyl-1H-pyrazole

A 3L 3-neck round bottom flask equipped with a mechanical stirrer, a temperature controller, and a nitrogen inlet was charged with potassium tert-butoxide (Aldrich 95percent, 84.6 g, 0.716 mol) and DMSO (400 mL, 4.x.) at room temperature and stirred for 15 minutes. To this solution was added pyrazole 2 (59 g, 0.719 mol) followed by a DMSO rinse (50 mL, 0.5.x.). The resulting orange turbid solution was stirred for 15 minutes and fluoride 1 (100 g, 0.477 mol) was added followed by a DMSO rinse (50 mL, 0.5.x.). This mixture was then heated to 50° C. and held for 5 hours at this temperature. After cooling to room temperature, the reaction mixture was diluted with MTBE (750 mL), and water (500 mL) was added to give a brown turbid mixture. After 15 minutes stirring, the organic layer was separated and sequentially washed with 1 N HCl (250 mL), brine (250 mL), and water (250 mL). Solution assay of organic layer was carried out using GC (conversion >99percent, solution yields of 3 and its regioisomer 4 were 83percent and 17percent, respectively). The MTBE solution was then concentrated under vacuum to a total volume of about 200 mL (KF showed 0.737percent water). THF (500 mL) was added, and concentrated to 2.x. solution (KF=0.158percent). THF addition-concentration sequence was repeated to give a 2.x. solution (KF=0.023percent), which used directly in the next step.Analytical samples of compounds 3 and 4 were purified by column chromatography and characterized: Compound 3: white crystals; M.p.: 76° C. (DSC onset temperature). .1. Preparation of 1-(4-Chloro-2-(3-methyl-1H-pyrazol-1-yl)phenyl)-2, 2, 2-trifluoroethanone A 3 L 3-neck round bottom flask equipped with a mechanical stirrer, a temperature controller, and a nitrogen inlet was charged with potassium tert-butoxide (Aldrich 95percent, 84.6 g, 0.716 mol) and DMSO (400 mL, 4.x.) at room temperature and stirred for 15 minutes. To this solution was added pyrazole 2 (59 g, 0.719 mol) followed by a DMSO rinse (50 mL, 0.5.x.). The resulting orange turbid solution was stirred for 15 min and fluoride 1 (100 g, 0.477 mol) was added followed by a DMSO rinse (50 mL, 0.5.x.). This mixture was then heated to 50° C. and held for 5 hours at this temperature. After cooling to room temperature, the reaction mixture was diluted with MTBE (750 mL), and water (500 mL) was added to give a brown turbid mixture. After 15 min stirring, the organic layer was separated and sequentially washed with 1 N HCl (250 mL), brine (250 mL), and water (250 mL). Solution assay of organic layer was carried out using GC (conversion >99percent, solution yields of 3 and its regioisomer 4 were 83percent and 17percent, respectively). The MTBE solution was then concentrated under vacuum to a total volume of about 200 mL (KF showed 0.737percent water). THF (500 mL) was added, concentrated to 2.x. solution (KF=0.158percent). THF addition-concentration sequence was repeated to give a 2.x. solution (KF=0.023percent) which used directly in the next step.Analytical samples of compounds 3 and 4 were purified by column chromatography and characterized: Compound 3: white crystals;

Molecular Weight:271.54
XLogP3:3.6
Hydrogen Bond Acceptor Count:1
Rotatable Bond Count:1
Exact Mass:269.95594
Monoisotopic Mass:269.95594
Topological Polar Surface Area:17.8
Heavy Atom Count:14
Complexity:203
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes