1,3-DibroMo-5-isopropoxybenzene

Synthesis of intermediate I-a: l , 3-dibromo-5-isopropoxy-benzeneTo a solution of NaH 60 percent dispersion in mineral oil (1.89 g, 47.25 mmol) in dry DMF (20 mL) under inert atmosphere was added dropwise at 0°C zSynthesis of Intermediate 1)Molecular Weight: 293.98 [00528] In a 3-neck 100 mL round-bottomed flask, 3, 5-dibromo phenol (5 g, 1 eq.) and KTo a stirred solution of 3, 5- dibromophenol (3 g, 11.91 mmol) in DMF (15 mL) was added potassium carbonate (3.29 g, 23.82 mmol, 1.44 mL) at room temperature and the reaction was stirred for 30 minutes. To this reaction mixture, 2-iodopropane (2.43 g, 14.29 mmol, 1.43 mL) was added dropwise and the resulting reaction mixture was stirred at 80-90C. TLC (mobile phase of ethyl acetate: n-hexane (1 :9)) confirmed that the starting material was consumed after 5 hours and which point the reaction was quenched with an ice-water slurry and the organics were extracted by ethyl acetate (50 mL x 3) The combined organic layers were dried over anhydrous sodium sulfate and concentrated under reduced pressure to obtain crude reaction mass that was subjected to column chromatography using combi-flash (eluted in 2-3% ethyl acetate in hexane to afford l, 3-dibromo-5-isopropoxy-benzene (3.2 g, 10.88 mmol, 91.40% yield) as clear liquid. m/z= 293.To a stirred solution of l, 3-dibromo-5-isopropoxy-benzene (500 mg, 1.70 mmol) in toluene (15 mL) w'ere added lH-pyrazole-4-carbaldehyde (179.77 mg, 1 87 mmol) and potassium phosphate tribasic anhydrous (722.05 mg, 3.40 mmol) and the reaction was degassed with N?. for 10 minutes. Copper (1) iodide (64.78 mg, 340.16 umol, 1 1.53 uL) and N, N'-dimethyl cyclohexane- 1 , 2-diamine (48.38 mg, 340.16 umol) were added to the reaction and the reaction was again degassed for 10 minutes. The reaction was heated to 130 C for 16 hours in a sealed tube at which point TLC confirmed the formation of product. The reaction was cooled and diluted with water and EtOAc. The organics was separated and aqueous part was extracted with EtOAc. The combined organics was washed with water and brine, dried over Na2S04, and concentrated to afford crude compound that was purified by combi-flash using 20-50% EtOAc in hexane to afford l-(3-bromo-5- isopropoxy-phenyl)-lH-pyrazole-4-carbaldehyde (190 mg, 583.84 umol, 34 33% yield, 95% purity, 000) as brown solid m/z = 309.Synthesis of intermediate I-b: 3-bromo-5-isopropoxy-benzaldehydeTo a solution of I-a (4.630 g, 15.75 mmol) in dry Et20 (60 mL) under inert atmosphere was added dropwise at -78C a solution of n-butyl lithium in dry Et20 (6.3 mL, 15.75 mmol). The reaction mixture was stirred at -78C for 0.5 h. Then, dry DMF (1.35 mL) was added dropwise at -78C and the temperature was allowed to reach -40C over 1.5 h. A solution of HC1 (3N) was added and the crude product was extracted with Et20 (2 times), the organic layer was washed with water, then with a saturated solution of NaCl, dried over MgS04 and concentrated to give I-b as yellow oil in 82% yield. 1H RMN (300 MHz, CDC13) delta 9.89 (s, 1H), 7.54 (m, 1H), 7.29 (m, 2H), 4.60 (dt, J = 12.1, 6.0 Hz, 1H), 1.36 (t, J= 6.0 Hz, 6H).

Molecular Weight:293.98
XLogP3:4.1
Hydrogen Bond Acceptor Count:1
Rotatable Bond Count:2
Exact Mass:293.90779
Monoisotopic Mass:291.90984
Topological Polar Surface Area:9.2
Heavy Atom Count:12
Complexity:129
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes