1-bromo-2,3-dimethylbenzene

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: The acetylated thiol 17 (500 mg, 1.4 mmol) was dissolved in methanol (2 mL) and NaOH was added (1.6 mL, 1M aqueous), followed by bromoxilene (300 mg, 1.62 mmol). After 20 min most of the starting material has disappeared (monitored by TLC). The solution was carefully neutralized with dilute HCl. The volatiles were removed in vacuo and the residue was extracted with Cl2CH2 (3×) The organic layer was washed with brine and dried over Na2SO4. The crude product was purified by flash column chromatography (silica, 5% to 20% ethyl acetate/hexane) to give the desired ester 18 (480 mg, 79%) as a white solid, which crystallized. mp 97°-98° C. (ether-hexane); [α]20D =-171.8° (c=1.05, CHCl3); 1H NMR (CDCl3).δ1.384 (s, 9H), 2.326 (s, 3H), 3.393 (d, J=13 Hz, 1H), 3.551 (d, J=13 Hz, 1H), 3.572 (s, 3H, OCH3), 4.126 (d,J=5.4 Hz, H-3), 4.630 (dd, J=8.8, 5.8 Hz, 1H, H-2), 5.220 (bd, J=8.8 Hz, 1H, H--N), 7.028-7.107 (m, 4H), 7.291-7.362 (m, 5H); 13C NMR (CDCl3).δ21.0, 28.3, 35.5, 51.6, 52.1, 57.5, 80.1, 127.8, 128.5, 128.7, 128.9, 129.2, 134.3, 136.9, 138.4, 154.7, 170.8; MS m/z 316 [M+H]+ ; Anal. Calcd for C23H29O4NS.1/4H2O: C, 65.76; H, 7.08; N, 3.33. Found: C, 65.59; H, 7.03; N, 3.36. The volatiles were removed in vacuo the residue was extracted with Cl2CH2 (3×) The organic layer was washed with brine dried over Na2SO4 The crude product was purified by flash column chromatography (silica, 5% to 20% ethyl acetate/hexane)

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: The acetylated thiol 17 (500 mg, 1.4 mmol) was dissolved in methanol (2 mL) and NaOH was added (1.6 mL, 1M aqueous), followed by bromoxilene (300 mg, 1.62 mmol). After 20 min most of the starting material has disappeared (monitored by TLC). The solution was carefully neutralized with dilute HCl. The volatiles were removed in vacuo and the residue was extracted with Cl2CH2 (3×) The organic layer was washed with brine and dried over Na2SO4. The crude product was purified by flash column chromatography (silica, 5% to 20% ethyl acetate/hexane) to give the desired ester 18 (480 mg, 79%) as a white solid, which crystallized. mp 97°-98° C. (ether-hexane); [α]20D =-171.8° (c=1.05, CHCl3); 1H NMR (CDCl3).δ1.384 (s, 9H), 2.326 (s, 3H), 3.393 (d, J=13 Hz, 1H), 3.551 (d, J=13 Hz, 1H), 3.572 (s, 3H, OCH3), 4.126 (d,J=5.4 Hz, H-3), 4.630 (dd, J=8.8, 5.8 Hz, 1H, H-2), 5.220 (bd, J=8.8 Hz, 1H, H--N), 7.028-7.107 (m, 4H), 7.291-7.362 (m, 5H); 13C NMR (CDCl3).δ21.0, 28.3, 35.5, 51.6, 52.1, 57.5, 80.1, 127.8, 128.5, 128.7, 128.9, 129.2, 134.3, 136.9, 138.4, 154.7, 170.8; MS m/z 316 [M+H]+ ; Anal. Calcd for C23H29O4NS.1/4H2O: C, 65.76; H, 7.08; N, 3.33. Found: C, 65.59; H, 7.03; N, 3.36. The volatiles were removed in vacuo the residue was extracted with Cl2CH2 (3×) The organic layer was washed with brine dried over Na2SO4 The crude product was purified by flash column chromatography (silica, 5% to 20% ethyl acetate/hexane)

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A mixture of 2-chloro-5-methylpyrimidin-4-amine (143.6 mg, 1 mmol), 1-bromo-2,3-dimethylbenzene (222 mg, 1.2 mmol), Pd2(dba)3 (92 mg, 0.1 mmol), Xantphos (174 mg, 0.3 mmol) and cesium carbonate (1.3 g, 4 mmol) were suspended in dioxane (150 mL) and heated at reflux under the argon atmosphere for 20 h. The mixture was filtered and the filtrate concentrated in vacuo. The residue was dissolved in EtOAc (10 mL) and added hexanes (100 mL). The solid was collected by filtration and washed with hexanes to afford the crude title compound as a yellow solid. heated at reflux under the argon atmosphere for 20 h The mixture was filtered the filtrate concentrated in vacuo The residue was dissolved in EtOAc (10 mL) added hexanes (100 mL) The solid was collected by filtration washed with hexanes

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A mixture of 2-chloro-5-methylpyrimidin-4-amine (143.6 mg, 1 mmol), 1-bromo-2,3-dimethylbenzene (222 mg, 1.2 mmol), Pd2(dba)3 (92 mg, 0.1 mmol), Xantphos (174 mg, 0.3 mmol) and cesium carbonate (1.3 g, 4 mmol) were suspended in dioxane (150 mL) and heated at reflux under the argon atmosphere for 20 h. The mixture was filtered and the filtrate concentrated in vacuo. The residue was dissolved in EtOAc (10 mL) and added hexanes (100 mL). The solid was collected by filtration and washed with hexanes to afford the crude title compound as a yellow solid. heated at reflux under the argon atmosphere for 20 h The mixture was filtered the filtrate concentrated in vacuo The residue was dissolved in EtOAc (10 mL) added hexanes (100 mL) The solid was collected by filtration washed with hexanes

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A mixture of 2-chloro-5-methylpyrimidin-4-amine (143.6 mg, 1 mmol), 1-bromo-2,3-dimethylbenzene (222 mg, 1.2 mmol), Pd2(dba)3 (92 mg, 0.1 mmol), Xantphos (174 mg, 0.3 mmol) and cesium carbonate (1.3 g, 4 mmol) were suspended in dioxane (150 mL) and heated at reflux under the argon atmosphere for 20 h. The mixture was filtered and the filtrate concentrated in vacuo. The residue was dissolved in EtOAc (10 mL) and added hexanes (100 mL). The solid was collected by filtration and washed with hexanes to afford the crude title compound as a yellow solid. heated at reflux under the argon atmosphere for 20 h The mixture was filtered the filtrate concentrated in vacuo The residue was dissolved in EtOAc (10 mL) added hexanes (100 mL) The solid was collected by filtration washed with hexanes

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A mixture of 3-bromo-o-xylene (15 g, 81 mmol), N-bromo succinimid (15.1 g, 85.1 mmol), dibenzoylperoxid (0.65 g) and tetrachloromethane (150 ml) was refluxed for 5 hours. After filtration the filtrate was washed with sodium hydrogensulfite and water. The organic layer was dried over sodium sulfate and evaporated in vacuo. Chromatography (SiO2) (petroleum ether:ethyl acetate, 100:4) gave a 16.8 g fraction of a mixture containing 45% of the title compound. This mixture was used without further purification. was refluxed for 5 hours After filtration the filtrate was washed with sodium hydrogensulfite and water The organic layer was dried over sodium sulfate evaporated in vacuo Chromatography (SiO2) (petroleum ether:ethyl acetate, 100:4) gave a 16.8 g fraction of a mixture

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: The acetylated thiol 17 (500 mg, 1.4 mmol) was dissolved in methanol (2 mL) and NaOH was added (1.6 mL, 1M aqueous), followed by bromoxilene (300 mg, 1.62 mmol). After 20 min most of the starting material has disappeared (monitored by TLC). The solution was carefully neutralized with dilute HCl. The volatiles were removed in vacuo and the residue was extracted with Cl2CH2 (3×) The organic layer was washed with brine and dried over Na2SO4. The crude product was purified by flash column chromatography (silica, 5% to 20% ethyl acetate/hexane) to give the desired ester 18 (480 mg, 79%) as a white solid, which crystallized. mp 97°-98° C. (ether-hexane); [α]20D =-171.8° (c=1.05, CHCl3); 1H NMR (CDCl3).δ1.384 (s, 9H), 2.326 (s, 3H), 3.393 (d, J=13 Hz, 1H), 3.551 (d, J=13 Hz, 1H), 3.572 (s, 3H, OCH3), 4.126 (d,J=5.4 Hz, H-3), 4.630 (dd, J=8.8, 5.8 Hz, 1H, H-2), 5.220 (bd, J=8.8 Hz, 1H, H--N), 7.028-7.107 (m, 4H), 7.291-7.362 (m, 5H); 13C NMR (CDCl3).δ21.0, 28.3, 35.5, 51.6, 52.1, 57.5, 80.1, 127.8, 128.5, 128.7, 128.9, 129.2, 134.3, 136.9, 138.4, 154.7, 170.8; MS m/z 316 [M+H]+ ; Anal. Calcd for C23H29O4NS.1/4H2O: C, 65.76; H, 7.08; N, 3.33. Found: C, 65.59; H, 7.03; N, 3.36. The volatiles were removed in vacuo the residue was extracted with Cl2CH2 (3×) The organic layer was washed with brine dried over Na2SO4 The crude product was purified by flash column chromatography (silica, 5% to 20% ethyl acetate/hexane)

Conditions: temp:-78.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of 3-bromo-o-xylene (500 mg, 2.7 mmol) in THF (15 mL) at −78° C. under N2 was slowly added 1.7 M tert-butyl lithium in pentane (1.77 mL, 3.0 mmol). This was stirred at −78° C. for 30 m. To the reaction mixture was added B(OiPr)3 (2.05 g, 11 mmol), and the reaction mixture was raised to 20° C. and stirred for 2 h. 3 N HCl (10 mL) was added to the reaction mixture and the acidic solution was stirred for 90 m. The reaction mixture was extracted using EtOAc (4×50 mL), and the organic solution was extracted using a 1 N solution of NaOH (100 mL). The aqueous solution was washed with Et2O (2×50 mL), acidified to pH 1 using concentrated HCl, and then extracted using EtOAc (4×50 mL). The organic solution was then washed with brine (100 mL), dried over MgSO4 and concentrated in vacuo to afford 2,3-dimethylphenylboronic acid compound (750 mg, 45%) as a white solid. at −78° C. the reaction mixture was raised to 20° C. stirred for 2 h the acidic solution was stirred for 90 m The reaction mixture was extracted the organic solution was extracted The aqueous solution was washed with Et2O (2×50 mL) extracted The organic solution was then washed with brine (100 mL) dried over MgSO4 concentrated in vacuo

Conditions: temp:-78.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of 3-bromo-o-xylene (500 mg, 2.7 mmol) in THF (15 mL) at −78° C. under N2 was slowly added 1.7 M tert-butyl lithium in pentane (1.77 mL, 3.0 mmol). This was stirred at −78° C. for 30 m. To the reaction mixture was added B(OiPr)3 (2.05 g, 11 mmol), and the reaction mixture was raised to 20° C. and stirred for 2 h. 3 N HCl (10 mL) was added to the reaction mixture and the acidic solution was stirred for 90 m. The reaction mixture was extracted using EtOAc (4×50 mL), and the organic solution was extracted using a 1 N solution of NaOH (100 mL). The aqueous solution was washed with Et2O (2×50 mL), acidified to pH 1 using concentrated HCl, and then extracted using EtOAc (4×50 mL). The organic solution was then washed with brine (100 mL), dried over MgSO4 and concentrated in vacuo to afford 2,3-dimethylphenylboronic acid compound (750 mg, 45%) as a white solid. at −78° C. the reaction mixture was raised to 20° C. stirred for 2 h the acidic solution was stirred for 90 m The reaction mixture was extracted the organic solution was extracted The aqueous solution was washed with Et2O (2×50 mL) extracted The organic solution was then washed with brine (100 mL) dried over MgSO4 concentrated in vacuo