2-[(3-chlorophenyl)Methyl]-4,4,5,5-tetraMethyl-1,3,2-dioxaborolane

Under the condition that magnesium turnings are added in situ, The boron esterification of p-chlorobenzyl chloride and pinacol diboron catalyzed by Fe(acac)3 was carried out by adding catalyst (3.5 mg, 0.010 mmol, 2 molpercent) in succession under argon atmosphere.Bis(pinacolato)boronic acid ester (127.0 mg, 0.5 mmol), Magnesium turnings (16.8 mg, 0.7 mmol), Tetrahydrofuran (1 ml) was added after the addition of p-chlorobenzyl chloride (157 μl, 1.35 mmol) at -10°C.The reaction was carried out for 5 hours, and the reaction was terminated by adding water. The reaction product was extracted with ethyl acetate and the yield was 81percent by gas chromatography.Example 8Preparation of pinacol ester of 4-chlorobenzylboronic acid Magnesium turnings (2.4 mg, 0.1 mmol, 10 mol percent) are introduced into a 2 necks Schlenk-type flask, provided with a magnetic stirring bar and topped by a coolant, then 10 ml of distilled THF are added. Triethylamine (59 mg, 1 mmol) and pinacolborane (0.384 g, 3 mmol) are introduced therein. 4-chlorobenzyl bromide (0.207 g, 1 mmol) dissolved into 10 ml of distilled THF is then added drop by drop in the solution using a dropping funnel. Thereafter, the reactive mixture is stirred for approximately 15 hours at THF reflux (65° C.).At the end of the reaction, the crude reaction product is hydrolyzed by 20 ml of water neutral and extracted by diethyl ether (3.x.40 ml). The joined organic phases are washed by 2.x.ml of neutral water then dried on MgSOTo a 10 mL reaction tube equipped with a magnet was added 0.4 mg (0.8 mmol) of 4-chlorophenylboronic acid, 0.4 mL (0.8 mmol) of trimethylsilyl diazomethane (2 M n-hexane solution), 1 mL of toluene was added to the system, The stopper was stoppered and reacted on an electromagnetic heating stirrer at 40 ° C for 2 hours.Followed by addition of 71 mg (0.6 mmol) of pinacol (dissolved in 1 mL of 1, 4-dioxane), 0.3 mL of tetrabutylammonium fluoride (1 M tetrahydrofuran solution) and 200 uL of water at 40 ° C, To continue for 2 hours.After completion of the reaction, the organic solvent was removed by a rotary evaporator and purified by column chromatography4-chlorobenzyl boronic acid pinacol ester, its structure is as follows:The compound was a colorless liquid in a yield of 85percent with the following NMR data:4-Chlorobenzyl bromide (640 mg, 3.12 mmol), boronic acid pinacol ester (1.2 mg, 10 mmol), CuI (97 mg, 0.5 mmol), LiOMe (365 mg, 4.68 mmol), PPh3 (106 mg, 0.41 mmol) and DMF (15 mL) were added to a 100 mL reaction flask. After replacing three times with nitrogen, the reaction was carried out at room temperature for 14 h, and TLC was monitored until the starting material was completely reacted. The reaction solution was poured into 100 mL of water, and the CuI was removed by filtration and washed three times with EA. The filtrate was collected and separated, and the aqueous phase was extracted with EA (60 mL*3). The title compound 30b (250 mg, 31percent) was obtained. Under the condition that magnesium turnings are added in situ, The boron esterification of p-chlorobenzyl chloride and pinacol diboron catalyzed by Fe(acac)3 was carried out by adding catalyst (3.5 mg, 0.010 mmol, 2 mol%) in succession under argon atmosphere.Bis(pinacolato)boronic acid ester (127.0 mg, 0.5 mmol), Magnesium turnings (16.8 mg, 0.7 mmol), Tetrahydrofuran (1 ml) was added after the addition of p-chlorobenzyl chloride (157 mul, 1.35 mmol) at -10C.The reaction was carried out for 5 hours, and the reaction was terminated by adding water. The reaction product was extracted with ethyl acetate and the yield was 81% by gas chromatography.Intermediate 3g (E)-N'-(6-lodo-5-methyl-[1 , 2, 5]oxadiazolo[3, 4-b]pyridin-7-yl)-N, N- dimethylmethanimidannide (50 mg; 0.151 mmol), 2-(4-Chloro-benzyl)-4, 4, 5, 5- tetramethyl-[1 , 3, 2]dioxaborolane (0.076 mg; 0.302 mmol), cesium carbonate (147 mg; 0.453 mmol) are dissolved in 2 ml_ tetrahydrofurane/water (9/1 ). Argon is bubbled into the mixture and [1 , 1?-bis(di-tert-butylphosphino)-ferrocene]palladium (II) dichloride (147 mg; 0.453 mmol) is added and the mixture is stirred at 80C for 18 h. It is purified by silica gel chromatography (eluent: cyclohexane/ethyl acetate 0% -> 80%).Yield: 18 mg (37 % of theory)Mass spectrometry (ESI+): m/z = 330 [M+H]+HPLC (Method 1 ): Retention time = 1 .101 min.General procedure: General Procedure: A glass test tube, which was equipped with a magnetic stir bar and fitted with a stopper, was charged with Pd(COD)Cl2 (14.3 mg, 0.05 mmol) and RuPhos (46.7 mg, 0.10 mmol). Cs2CO3 (488.7 mg, 1.5 mmol, 3.0 equiv.), benzylboronic acid pinacol ester (1.0 mmol, 2.0 equiv.), N-Boc-3-iodo-azetidine (283.1 mg, 0.5 mmol, 1.0 equiv.) and 3 mL 1, 4-dioxane/H2O (1:1). The reaction mixture was purged with argon gas three times. Under argon, the reaction mixture was allowed to stir at 80 oC for 24 h. The progress of the reaction was monitored by GC-MS. After cooling to room temperature, the reaction mixture was diluted with ethyl acetate (15 mL) and washed with saturated brine (3×10 mL). The aqueous layer was extracted with ethyl acetate (2×15 mL). The combined organic layers were dried over MgSO4, concentrated in vacuo, and purified by silica gel flash chromatography.Compound 30b (190 mg, 0.50 mmol), p-chlorobenzylboronic acid pinacol ester (250 mg, 0.99 mmol), NaHCO3 (166 mg, 1.98 mmol), DMF (4 mL), H2O (1 mL) was added to a reaction flask, and Pd(dppf)Cl2 (104 mg, 0.14 mmol) was added after nitrogen substitution.After nitrogen substitution, the temperature was raised to 90 C, and TLC was monitored until the reaction of the crude material was complete. After cooling to room temperature, the reaction solution was poured into water and extracted with DCM.The title compound 30d (80 mg, 38%) was obtained.General procedure: Procedure1: An oven-dried three-neck round bottom flask was fitted with a condenser. Pd(OAc)2 (145.7 mg, 0.649 mmol), dppf (359.5 mg, 0.649 mmol) bis(pinacolato)diboron (4.120 g, 16.22 mmol) and potassium acetate (1.592 g, 16.22 mmol) were added to the flask. The flask was evacuated and backfilled with argon (this process was repeated a total of 3 times). Benzyl bromide (2.000 g, 11.69 mmol) was added followed by the addition of 1, 4-dioxane (30 mL). The reaction mixture was heated to 100 for 4 h and 65 for 15 h and then cooled to room temperature. The reaction mixture was passed through a plug of silica gel eluting with EtOAc and washed with saturated brine (3×50 mL). The organic layers were dried over MgSO4, concentrated in vacuo, and the residue was purified by silica gel flash chromatography.4-Chlorobenzyl bromide (640 mg, 3.12 mmol), boronic acid pinacol ester (1.2 mg, 10 mmol), CuI (97 mg, 0.5 mmol), LiOMe (365 mg, 4.68 mmol), PPh3 (106 mg, 0.41 mmol) and DMF (15 mL) were added to a 100 mL reaction flask. After replacing three times with nitrogen, the reaction was carried out at room temperature for 14 h, and TLC was monitored until the starting material was completely reacted. The reaction solution was poured into 100 mL of water, and the CuI was removed by filtration and washed three times with EA. The filtrate was collected and separated, and the aqueous phase was extracted with EA (60 mL*3). The title compound 30b (250 mg, 31%) was obtained.

Molecular Weight:252.55
Hydrogen Bond Acceptor Count:2
Rotatable Bond Count:2
Exact Mass:252.1088377
Monoisotopic Mass:252.1088377
Topological Polar Surface Area:18.5
Heavy Atom Count:17
Complexity:265
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes