8-isoquinolinyl-boronic acid

Yellow to beige solid

To a solution of 8-bromoisoquinoline (2.0 g, 9.6 mmol) in THE (40 mL) was added dropwise n-BuLi (2.5 M, 4.2 mL, 10.6 mmol) at -78 °C under nitrogen. After 1 hour, B(OMe)3 (2.0 g, 19.2 mmol) was added to the reaction and the mixture was warmed to 0 °C for 1 hour. The reaction was quenched by aqueous NaHCO3 andextracted with EtOAc 3 times. The combined organic layers were washed with brine, dried over Na2SO4 and concentrated. The residue was purified by silica gel column chromatography to give 75 (680 mg, 41percent) as a slightly yellow solid. LCMS (m/z: m+1):174.1.General procedure: Benzyl bromide 3 (1.0 eq), the appropriate boronic acid (1.5 eq), Pd(dppf)Cl2 (0.1 eq), and K2CO3(3.0 eq) were combined in a microwave vessel equipped with a teflon stirbar. The system was flushedwith argon. A degassed mixture of 3:1 acetone:water (3 mL) was added, and the reaction was heated ina microwave to 100 C for 30 min. The product was purified via silica gel chromatography in ethylacetate/hexanes.A mixture of 75 (680 mg, 3.93 mmol), 43 (1306 mg, 7.86 mmol), Cu(OAc)2 (2142mg, 11 .8 mmol), Et3N (2387 mg, 23.6 mmol) and 4A MS (5.0 g) in CH2CI2 (50 mL) wasstirred at room temperature under air for 3 days. The reaction was filtered and washed with CH2CI2. The filtrate was concentrated and purified by silica gel column chromatography (CH2CI2/MeOH) and then silica gel prep-TLC (petroleum ether/EtOAc) to give 76 (230 mg, 20%) as a slightly yellow solid. LCMS (m/z: m+1): 294.2.To a solution of 8-bromoisoquinoline (2.0 g, 9.6 mmol) in THF (40 mL) was added n-BuLi (2.5 M, 4.2 mL, 10.6 mmol) dropwise at -78C under nitrogen. After 1 h, B(OMe)3 (2.0g, 19.2 mmol) was added to the reaction and the mixture was warmed to 0C for 1 h. Thereaction was quenched by aqueous NaHCO3 and extracted with EtOAc three times. Thecombined organic layers were washed with brine, dried over Na2SO4 and concentrated. Theresidue was purified by silica gel column chromatography to give 59 (680 mg, 41%) as aslightly yellow solid LCMS (m/z: m+1): 174.1. A mixture of 59 (680 mg, 3.93 mmol), 56 (1306mg, 7.86 mmol), Cu(OAc)2 (2142 mg, 11.8 mmol), Et3N (2387 mg, 23.6 mmol) and 4A MS(5.0 g) in CH2Cl2 (50 mL) was stirred at room temperature under air for 3 days. The reactionwas filtered and washed with CH2Cl2. The filtrate was concentrated and purified by silica gelcolumn chromatography (CH2Cl2/MeOH) and then silica gel prep-TLC (petroleumether/EtOAc) to give 60 (230 mg, 20%) as a slightly yellow solid. LCMS (m/z: m+1): 294.2.To a solution of this material (230 mg, 0.784 mmol) in MeOH/H2O (3/0.5 mL) was addedNaOH (63 mg, 1.57 mmol). The reaction was stirred at room temperature for 2 days. Water (3mL) was added to the reaction and then acidified by 1M HCl. The resulting solution wasconcentrated under reduced pressure to give 61 as a slightly yellow solid that was used in nextstep without further purification. LCMS (m/z: m+1): 280.1. A mixture of this material (218mg, 0.784 mmol theoretical amount from previous step), 17 (255 mg, 0.941 mmol), HATU(596 mg, 1.57 mmol) and DIEA (607 mg, 4.70 mmol) in DMF (3 mL) was heated at 70C overnight. After cooling, the reaction mixture was directly purified by reverse prep-HPLC andsilica gel prep-TLC to give 3d (113 mg, 27% over two steps) as a yellow solid.To a solution of 8-bromoisoquinoline (2.0 g, 9.6 mmol) in THE (40 mL) was added dropwise n-BuLi (2.5 M, 4.2 mL, 10.6 mmol) at -78 °C under nitrogen. After 1 hour, B(OMe)3 (2.0 g, 19.2 mmol) was added to the reaction and the mixture was warmed to 0 °C for 1 hour. The reaction was quenched by aqueous NaHCO3 andextracted with EtOAc 3 times. The combined organic layers were washed with brine, dried over Na2SO4 and concentrated. The residue was purified by silica gel column chromatography to give 75 (680 mg, 41percent) as a slightly yellow solid. LCMS (m/z: m+1):174.1.General procedure: All reagents were purchased from Aldrich and Frontier Scientific. For thermodynamic binding experiments, an RF-1501 Shimadzu fluorometer was used. For stopped-flow experiments, an Applied Photophysics RX2000 Rapid Mixing stopped-flow unit with FluoromaxIIII fluorometer (Horiba) was used. The dead time for this instrument is 0.05 s. All kinetic experiments were conducted in phosphate buffer (0.1 M) at pH 7.4 and at room temperature. Kinetic measurements were performed under pseudo first-order conditions. In a fixed concentration of IQBAs, different concentrations of sugars were mixed within a short time period. All the reaction curves were fitted using formula (1) in Origin 8. Using formula (2), Kobs can be calculated. Values for kon and koff were calculated using formula (3) by varying [S], the substrate concentration.General procedure: All reagents were purchased from Aldrich and Frontier Scientific. For thermodynamic binding experiments, an RF-1501 Shimadzu fluorometer was used. For stopped-flow experiments, an Applied Photophysics RX2000 Rapid Mixing stopped-flow unit with FluoromaxIIII fluorometer (Horiba) was used. The dead time for this instrument is 0.05 s. All kinetic experiments were conducted in phosphate buffer (0.1 M) at pH 7.4 and at room temperature. Kinetic measurements were performed under pseudo first-order conditions. In a fixed concentration of IQBAs, different concentrations of sugars were mixed within a short time period. All the reaction curves were fitted using formula (1) in Origin 8. Using formula (2), Kobs can be calculated. Values for kon and koff were calculated using formula (3) by varying [S], the substrate concentration.General procedure: All reagents were purchased from Aldrich and Frontier Scientific. For thermodynamic binding experiments, an RF-1501 Shimadzu fluorometer was used. For stopped-flow experiments, an Applied Photophysics RX2000 Rapid Mixing stopped-flow unit with FluoromaxIIII fluorometer (Horiba) was used. The dead time for this instrument is 0.05 s. All kinetic experiments were conducted in phosphate buffer (0.1 M) at pH 7.4 and at room temperature. Kinetic measurements were performed under pseudo first-order conditions. In a fixed concentration of IQBAs, different concentrations of sugars were mixed within a short time period. All the reaction curves were fitted using formula (1) in Origin 8. Using formula (2), Kobs can be calculated. Values for kon and koff were calculated using formula (3) by varying [S], the substrate concentration.

Molecular Weight:172.98
Hydrogen Bond Donor Count:2
Hydrogen Bond Acceptor Count:3
Rotatable Bond Count:1
Exact Mass:173.0648087
Monoisotopic Mass:173.0648087
Topological Polar Surface Area:53.4
Heavy Atom Count:13
Complexity:177
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes