4-CYCLOPROPOXYPHENYLBORONIC ACID

General procedure: To a solution of 3-bromo-6-[4-(propan-2-yloxy)phenyl]imidazo[1 , 2-a]pyridine (20 mg, 0.06 mmol) in 2 mL THF:Water 3:1 was added 4-cyclopropylboronic acid (12 mg, 0.072 mmol), potassium carbonate (5 mg, 0.18 mmol), and Pd(dppt)C12 dichloromethane complex (5mg, .006 mmol). The mixture was capped tightly and degassed by bubbling nitrogen through the septum for 5 minutes. The resultingsolution was heated to 100C for 15 minutes in a microwave reactor and allowed to cool. The mixture was then diluted with ethyl acetate, washed with water (2x) and brine (lx), dried over sodium sulfate, and evaporated. The crude oil was purified by flash chromatography on silica (3:7hexanes:ethyl acetate, isocratic) to provide 13 mg of the title compound as a light yellow oil.Dissolve 2-bromo-5H-thiazolo[5, 4-c]pyridin-4-one (0.218 g, 0.934 mmol) in dimethoxy ethane (5 mL) followed by addition of EtOH (1 mL) and water (1 mL). Add A- cylcopropoxyphenylboronic acid (prepare as described in Olofsson, K. et al, WO 2005123673) (0.185 g, 1.04 mmol) followed by 2M Na2CO3 (1 mL, 2 mmol). Allow dry argon gas to bubble through the reaction mixture for 15-20 min. Add Pd(P Ph3 )4 (33 mg, 0.27 mumol) and then warm to 85 0C under an argon atmosphere. After 18 h, evaporate the mixture to a slurry. Dilute the mixture with water and stir for one hour. Filter and wash the solids with diethyl ether, then water, and then diethyl ether again. Dry the solids at room temperature overnight to give the desired material as a brown solid (0.214 g, 80%). 1H NMR (300 MHz, DMSO-d6) delta 11.7 (bs, IH), 8.01 (d, 2H, J= 8.8 Hz), 7.42 (d, IH, J = 6.9 Hz), 7.18 (d, 2H, J= 8.8 Hz), 6.81 (d, IH, J= 6.9 Hz), 3.93 (m, IH), 0.80 (m, 2H), 0.67 (m, 2H).7?-BuLi (2. 5 M in hexane, 9.76 mL, 24.4 mmol) was added over 17 min to a solution of l-bromo-4-cyclopropoxybenzene (5.0 g, 23.4 mmol) in THF (80 mL) at -78 0C. After 40 min, B(OEt)3 (5.9 mL, 34.3 mmol) was added and the mixture was allowed to reach rt and was stirred at rt for 18 h. The mixture was cooled to 0 0C and HCl (aq, 1 M, 70 mL) was added. After 30 min the mixture was extracted with f-BuOMe (3x50 mL) and the combined extracts were washed with brine, dried (Na2SO4) and concentrated. The residue was washed with petroleum ether to yield the sub-title compound (1.5 g, 34 %).To a solution of 4-bromo-4-cyclopropoxybenzene (5.0 g, 23.4 mmol, see Example 39 (c)) THF (80 mL) at-78C was added n-BuLi (2.5 M solution in hexane; 9.76 mL, 24.4 mmol) over 17 min. After 40 min, B(OEt)3 (5.9 mL, 34.3 mmol) was added and the reaction was warmed to room temperature and stirred at ambient temperature for 18 h. After re-cooling to 0C, HCl (1M solution; 70 mL, aq. ) was added. After 30 min the mixture was extracted with t-BuOMe (3x50 mL), the combined organic extracts were washed with brine, dried (Na(at)S04) and concentrated. The residue was washed with light petrol and filtered yielding the sub-title compound (1.5 g, 34 %).

Molecular Weight:177.99
Hydrogen Bond Donor Count:2
Hydrogen Bond Acceptor Count:3
Rotatable Bond Count:3
Exact Mass:178.0801244
Monoisotopic Mass:178.0801244
Topological Polar Surface Area:49.7
Heavy Atom Count:13
Complexity:162
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes