B-(4-Cyano-3-methoxyphenyl)boronic acid

A 3-necked 1L round-bottomed flask was equipped with an overhead stirrer, and a nitrogen line. The flask was charged with 45.56 g (215 mmol) of 4-bromo-2-methoxybenzonitrile, 64 mL (277 mmol) of tri-isopropylborate and 500 mL of THF. The solution was cooled to -78°C in a dry-ice/acetone bath. n-Butyllithium (2.5M, 110 mL, 275 mmol) was added dropwise via addition funnel. The mixture was stirred for 30 minutes and 2N HCl was added. The mixture was stirred for an hour and poured into water. The mixture was extracted with Et20. The organic solution was backextracted with 1N NaOH. The aqueous layer was washed with Et2O and acidified with conc. HCl. The mixture was extracted with Et20. The organic extract was dried (MgSO4) and evaporated in vacuo to afford 20.77 g (55percent) of the product as a white solid. 1H NMR (500 MHz, d6-DMSO) δ 7.68 (d, 1H), 7.59 (s, 1H), 7.47 (d, 1H), 3.95 (s, 3H).General procedure: A mixture of the respective pyrimidine halide derivative (II) (0.15 mmol), the respective boronic acid derivative (III) (0.18 mmol), and K2003 2M (0.3 mL, 0.6 mmol) in ethanol (3 mL) is purged with argon, tetrakis5 (triphenylphosphine)-palladium (0.0075 mmol) is added, and the RM is heated at 9000 overnight. Alternatively, thereaction can be performed in a microwave apparatus, at 120C for 15- 30 mm. The RM is filtered through a 0.45 um Glass MicroFiber filter, washed with EtOH/MeCN and DMF. The filtrate is purified either by preparative HPLC or FC. Alternatively, it is diluted with water, if needed the pH is adjusted, and extracted with EtOAc (3x). The combined organic extracts are dried (MgSO4) and concentrated under reduced pressure. The residue is purified by preparative HPLC or by FC.The title compound is prepared according to the general procedure A described above, using the building block A.1.1. and A stirred mixture of 5-bromo-2-morpholinopyridin-4-amine (0.21 g, 0.82 mmol), dichlorobis(triphenylphosphine)palladium(II) (30.3 mg, 0.043 mmol), 4-cyano-3- methoxyphenylboronic acid (29.2 mg, 1.65 mmol), and 2.0M sodium carbonate (1.3 mL, 2.6 mmol) in 1, 4-dioxane (4.0 mL) was heated to 90 C. After 19 h, the reaction was cond under reduced pressure. The black solid was diluted with water. After three extractions with EtOAc, the organic extractions were dried over anhydrous sodium sulfate. After filtration and concentration, the residue was purified on silica gel (0-60 % EtOAc in hexanes) to afford a white solid as mostly or 4-(4-amino-6-morpholinopyridin-3-yl)-2-methoxybenzonitrile that was used without further purification.In a screw cap vial compound 311 (8-Bromo-2-cyclopropyl-5-methoxy-[l, 2, 4]triazolo[l, 5-a]pyridine) (0.025g, 0.093 mmol) was dissolved in DME (0.6 mL) and 1 M K2CO3 (0.2 mL) under argon. 4-CN-3-methoxyphenyl boronic acid (0.033g, 0.19 mmol) and Pd(PPh3J4 (0.005g, 0.005 mmol) were added. The suspension was shaken at 800C for 5 h after which brine was added, and the aqueous phase was extracted with DCM (x 3). The combined organic phases were dried, filtered and concentrated. The crude product was purified by flash chromatography, eluent DCM : EtOAc 9 : 1. This afforded the title compound as a solid. IH NMR (300 MHz, DMSO) delta 8.14 (d, J = 8.3 Hz, IH), 8.11 (d, J = 1.3 Hz, IH), 7.87 (dd, J = 8.1, 1.5 Hz, IH), 7.80 (d, J = 8.2 Hz, IH), 6.74 (d, J = 8.4 Hz, IH), 4.18 (s, 3H), 4.01 (s, 3H), 2.21 (tt, J = 8.0, 5.0 Hz, IH), 1.13 - 0.97 (m, 4H).In a tube was placed boronic acid 28 (35.4 mg, 200 mol), and tosyl protected azaindole 3 (65.5mg, 194 mumol), with sodium carbonate (61.8mg, 583mumol) and tetrakis(triphenylphosphine)palladium(0) (8.3mg, 7.2, mol). Water (323mg) and Ethylene glycol dimethyl ether (848mg) were added and the mixture was deoxygenated. The tube was sealed and heated to 160C for 10 minutes with magnetic stirring, utilizing microwave irradiation. The crude product was extracted with ethyl acetate and water. The organic were washed with brine, dried over sodium sulfate, filtered and concentrated to give crude product (83mg). The crude was purified via flash chromatography and eluted with a gradient from 1 : 1 ethyl acetate/hexane to 100% ethyl acetate to 4/4/1 ethyl acetate/hexane/7N ammonia in methanol to give 29 (42mg, 54%) and 30 (7.7 mg, 15%).A 3-necked 1L round-bottomed flask was equipped with an overhead stirrer, and a nitrogen line. The flask was charged with 45.56 g (215 mmol) of 4-bromo-2-methoxybenzonitrile, 64 mL (277 mmol) of tri-isopropylborate and 500 mL of THF. The solution was cooled to -78°C in a dry-ice/acetone bath. n-Butyllithium (2.5M, 110 mL, 275 mmol) was added dropwise via addition funnel. The mixture was stirred for 30 minutes and 2N HCl was added. The mixture was stirred for an hour and poured into water. The mixture was extracted with Et20. The organic solution was backextracted with 1N NaOH. The aqueous layer was washed with Et2O and acidified with conc. HCl. The mixture was extracted with Et20. The organic extract was dried (MgSO4) and evaporated in vacuo to afford 20.77 g (55percent) of the product as a white solid. 1H NMR (500 MHz, d6-DMSO) delta 7.68 (d, 1H), 7.59 (s, 1H), 7.47 (d, 1H), 3.95 (s, 3H).

Molecular Weight:176.97
Hydrogen Bond Donor Count:2
Hydrogen Bond Acceptor Count:4
Rotatable Bond Count:2
Exact Mass:177.0597233
Monoisotopic Mass:177.0597233
Topological Polar Surface Area:73.5
Heavy Atom Count:13
Complexity:213
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes