3-Carboxyphenylboronic acid pinacol ester

almost white to light beige crystalline powder

To a degassed souDon of 1, 4-doxane (0.1 M), under an atmosphere of ntrogen, was addedthe benzoc acid (1 eq.), bs(pnacoato)dthoron (1 .5 eq.), and KOAc (4.4 eq.) sequenUafly.The mixture was degassed once again and then PdC2(dppf) (5 mopercent) was added. Theresutng souUon was heated to 110°C overnight. The sovent was removed in vacuo to givea dark gummy residue, which was taken up nto EtOAc and H20. The organic ayer was separated and the aqueous was further extracted with EtOAc (2x). The combined organic ayers were washed with 2 M HC, dried over MgSO4 and concentrated in vacuo to give a dark brown sohd. The resutng sohd was trtu rated wth petroeum benzne to afford the Uflecompound. The foHowng compounds were made by the 8uzuk couphng method E Bl, Os 0BCO2HFaint brown scUd (89percent). 1H NMR (400 MHz, CDC3) 68.57 (s, 1H), 8.19 (ddd, J= 21.9, 11.8, 10.1 Hz, 1 H), 8.09 7.98 (m, 1 H), 7.57 7.38(m, 1H), 1.37 (s, 12H). 13C NMR (101 MHz, CDC3)6 171.66, 139.98, 136.60, 132.84, 128.71, 127.93, 84.21, 24.89. LCM8 B rt 3.67mn, m/z249.2 [M + H].General procedure: The boronic acids 26 and 27 (0.667 mmol) were dissolved in 6 mL of ethyl acetate and, stirring the solution, pinacol (0.667 mmol) was added. After 4 h the reaction was stopped adding anhydrous NaA solution of 4-dimethyl-aminopyridine (0.3 g, 2.42 mmol), N-(3- dimethylaminopropyl)-N'-ethylcarbodiimide (4.3 g, 22.17 mmol), 3-(4, 4, 5, 5-tetramethyl-1, 3, 2- dioxaborolan-2-yl)benzoic acid (5.0 g, 20.15 mmol) and 4-isopropyl-3-methyl-aniline hydrochloride (4.1 g, 22.17 mmol) in DCM (100 mL) was stirred at room temperature overnight. 3% aqueous citric acid solution (100 mL) and ethyl acetate (100 mL) were added to the reaction mixture and the reaction mixture was stirred for 5 minutes. The organic layer was washed sequentially with 1% aqueous citric acid (100 mL) and brine (100 mL), dried over sodium sulfate and concentrated under reduced pressure to give N-(4-isopropyl-3-methyl-phenyl)-3-(4, 4, 5, 5- tetramethyl-1, 3, 2-dioxaborolan-2-yl)benzamide (5.4 g, 14.2 mmol, 70.6% yield) as a light grey solid. Data: LC-MS (Method A) Rt: 8.05 min; m/z 380.3 (M+H)+.A solution of 4-dimethyl-aminopyridine (0.3 g, 2.42 mmol), N-(3- dimethylaminopropyl)-N'-ethylcarbodiimide (4.3 g, 22.17 mmol), 3-(4, 4, 5, 5-tetramethyl-1, 3, 2- dioxaborolan-2-yl)benzoic acid (5.0 g, 20.15 mmol) and 4-isopropyl-3-methyl-aniline hydrochloride (4.1 g, 22.17 mmol) in DCM (100 mL) was stirred at room temperature overnight. 3% aqueous citric acid solution (100 mL) and ethyl acetate (100 mL) were added to the reaction mixture and the reaction mixture was stirred for 5 minutes. The organic layer was washed sequentially with 1% aqueous citric acid (100 mL) and brine (100 mL), dried over sodium sulfate and concentrated under reduced pressure to give N-(4-isopropyl-3-methyl-phenyl)-3-(4, 4, 5, 5- tetramethyl-1, 3, 2-dioxaborolan-2-yl)benzamide (5.4 g, 14.2 mmol, 70.6% yield) as a light grey solid. Data: LC-MS (Method A) Rt: 8.05 min; m/z 380.3 (M+H)+.11h (0.9 g, 3.7 mmol), 1-hydroxybenzotriazole (0.5 g, 3.7 mmol) and N, N-dimethylformamide (4.1 mL) were sequentially added to a 25 mL single-necked flask. After cooled to 0 C, 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (0.8 g, 4.4 mmol) and diisopropylethylamine (0.9 g, 7.4 mmol) were added, stirred for 20 minutes and warmed to 13 C. 11g (0.4 g, 3.7 mmol) was added and the reaction was continued to stirred. The reaction was monitored by thin layer chromatography (ethyl acetate: n-hexane = 1:1) until the starting material disappeared. After water (8.1 ml) was added to the reaction mixture, the mixture was extracted with ethyl acetate (10 mL x 3), the combined organic phase was washed with saturated sodium chloride solution (10.2 ml), and concentrated to dry under reduced pressure. The crude product was purified by silica gel column product (ethyl acetate: n-hexane = 4: 1) to give a white solid compound 11f (1.0 g, purity 74.4%, yield 79.9%). MS m/z 257.0 [M-pinacol + H]+.11e (3.0 g, 8.1 mmol), 11h (2.4 g, 9.6 mmol), 1, 4-dioxane (30 ml), water (6.1 ml), potassium carbonate (2.2 g, 16.1 mmol) and Pd(dppf) Cl2·DCM (164 mg, 0.2 mmol) were added successively into a 100 ml three-necked flask. The system was replaced with nitrogen gas for three times under stirring, and then warmed to 90 C to reflux for 16 hours. After filtration, the filter cake was soaked with methanol (20 ml x 3) and discarded. The combined organic phase was concentrated to dry under reduced pressure, and the resulting solid was washed pulped with n-hexane (3 mL) - dichloromethane (12 ml) under 21 C for 2 h. After filtration, the filter cake was washed with dichloromethane (12.3 mL) and dried in a blast oven for 16 hours under 40 C to give light green solid compound 13a (3.3 g, purity 94.2%, yield 98.8%). 1H NMR (400 MHz, DMSO-d6) delta 9.40 (s, 1H), 8.56 (s, 1H), 8.46 (t, J= 1.8 Hz, 1H), 8.08-7.99 (m, 3H), 7.97 -7.80 (m, 4H), 7.61 (s, 1H), 7.36 (t, J = 7.6 Hz, 1H), 7.27 -7.19 (m, 2H), 6.97 (d, J = 8.9 Hz, 2H), 3.75 (t, J = 4.7 Hz, 4H), 3.08 (t, J = 4.8 Hz, 4H).A mixture of 7-bromopyrrolo[2, 1-f][1, 2, 4]triazin-4-amine (0.200 g, 0.939 mmol),

Molecular Weight:248.08
Hydrogen Bond Donor Count:1
Hydrogen Bond Acceptor Count:4
Rotatable Bond Count:2
Exact Mass:248.1219892
Monoisotopic Mass:248.1219892
Topological Polar Surface Area:55.8
Heavy Atom Count:18
Complexity:324
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes