3-bromo-2-methylbenzamide

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: 3-bromo-2-methylbenzamide (12.5 mg, 0.0584 mmol), N-(6-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)naphthalen-2-yl)thiophene-3-carboxamide (45.8 mg, 0.121 mmol), Fibercat palladium catalyst (Johnson-Matthey, 31.9 mg), and K2CO3 (2 M in water, 0.15 ml, 0.30 mmol) were combined in a microwave reaction vessel and 1,4-dioxane (0.7 ml) was added. The reaction tube was sealed and heated in the microwave (CEM microwave) at 60 Watts and 80 C for 10 minutes and then cooled to room temperature. The reaction was diluted with water (5 ml) and extracted with dichloromethane (3×10 ml) and EtOAc (10 ml). The organic extracts were combined, dried over magnesium sulfate, filtered, concentrated, and purified on HPLC (10%->95% MeCN/water with 0.1% TFA) to afford title compound (6.6 mg, 29%). MS (ESI pos. ion) m/z: 387 (M+H). Calc'd Exact Mass for C23H18N2O2S: 386. was added The reaction tube was sealed heated in the microwave (CEM microwave) at 60 Watts and 80 C for 10 minutes extracted with dichloromethane (3×10 ml) and EtOAc (10 ml) dried over magnesium sulfate filtered concentrated purified on HPLC (10%->95% MeCN/water with 0.1% TFA)

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

Procedure: 3-bromo-2-methylbenzamide (12.5 mg, 0.0584 mmol), N-(6-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)naphthalen-2-yl)thiophene-3-carboxamide (45.8 mg, 0.121 mmol), Fibercat palladium catalyst (Johnson-Matthey, 31.9 mg), and K2CO3 (2 M in water, 0.15 ml, 0.30 mmol) were combined in a microwave reaction vessel and 1,4-dioxane (0.7 ml) was added. The reaction tube was sealed and heated in the microwave (CEM microwave) at 60 Watts and 80 C for 10 minutes and then cooled to room temperature. The reaction was diluted with water (5 ml) and extracted with dichloromethane (3×10 ml) and EtOAc (10 ml). The organic extracts were combined, dried over magnesium sulfate, filtered, concentrated, and purified on HPLC (10%->95% MeCN/water with 0.1% TFA) to afford title compound (6.6 mg, 29%). MS (ESI pos. ion) m/z: 387 (M+H). Calc'd Exact Mass for C23H18N2O2S: 386. was added The reaction tube was sealed heated in the microwave (CEM microwave) at 60 Watts and 80 C for 10 minutes extracted with dichloromethane (3×10 ml) and EtOAc (10 ml) dried over magnesium sulfate filtered concentrated purified on HPLC (10%->95% MeCN/water with 0.1% TFA)

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

Procedure: 3-bromo-2-methylbenzoic acid (5.00 g, 23.3 mmol) was dissolved in DMF (41.6 ml) and EDC (5.46 g, 28.5 mmol), HOAt (3.97 g, 29.2 mmol), ammonium chloride (4.90 g, 90.9 mmol), and diisopropylethylamine (12.5 ml, 71.8 mmol) were added. The reaction was stirred at room temperature over the weekend, and then poured into water (100 ml). The resultant precipitate was filtered, washed with water, collected, and dried under vacuum to give the title compound (4.63 g, 93%). MS (ESI pos. ion) m/z: 214 (M+H). Calc'd Exact Mass for C8H8BrNO: 213. The resultant precipitate was filtered washed with water collected dried under vacuum

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

Procedure: 3-Bromo-2-methylbenzamide (1.4 g) was dissolved in dry THF (15 mL) under nitrogen, then Me2S.BH3 (94%, 1.34 mL) was added slowly. After stirred at room temperature for 1 h, the mixture was heated to 50° C. overnight. When 3-bromo-2-methylbenzamide disappeared, methanol was added dropwise until there was no more air bubble formed. Then 10 min later, 10% HCl was added dropwise, the mixture stirred for 1 h, and then solvent was removed. The white residual was recrystallized with iPrOH to obtain 1.1 g of the product. Yield: 35%. 1H NMR (400 MHz, DMSO-d6) δ 2.42 (s, 3H), 4.09 (s, 2H), 7.20 (t, J=7.8 Hz, 1H), 7.44 (d, J1=8.0 Hz, 1H), 7.63 (d, J1=7.6 Hz, 1H), 8.49 (br, 3H); 13C NMR (100 MHz, DMSO-d6) δ 18.8, 19.0, 46.1, 125.2, 127.4, 127.5, 129.0, 129.1, 132.1, 132.5, 134.7, 135.9, 136.1, 136.5; HPLC: retention time: 4.696 min; purity: 96.0%. BH3 (94%, 1.34 mL) was added slowly the mixture was heated to 50° C. overnight bubble formed the mixture stirred for 1 h solvent was removed The white residual was recrystallized with iPrOH

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

Procedure: 3-Bromo-2-methylbenzamide (1.4 g) was dissolved in dry THF (15 mL) under nitrogen, then Me2S.BH3 (94%, 1.34 mL) was added slowly. After stirred at room temperature for 1 h, the mixture was heated to 50° C. overnight. When 3-bromo-2-methylbenzamide disappeared, methanol was added dropwise until there was no more air bubble formed. Then 10 min later, 10% HCl was added dropwise, the mixture stirred for 1 h, and then solvent was removed. The white residual was recrystallized with iPrOH to obtain 1.1 g of the product. Yield: 35%. 1H NMR (400 MHz, DMSO-d6) δ 2.42 (s, 3H), 4.09 (s, 2H), 7.20 (t, J=7.8 Hz, 1H), 7.44 (d, J1=8.0 Hz, 1H), 7.63 (d, J1=7.6 Hz, 1H), 8.49 (br, 3H); 13C NMR (100 MHz, DMSO-d6) δ 18.8, 19.0, 46.1, 125.2, 127.4, 127.5, 129.0, 129.1, 132.1, 132.5, 134.7, 135.9, 136.1, 136.5; HPLC: retention time: 4.696 min; purity: 96.0%. BH3 (94%, 1.34 mL) was added slowly the mixture was heated to 50° C. overnight bubble formed the mixture stirred for 1 h solvent was removed The white residual was recrystallized with iPrOH

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

Procedure: 3-Bromo-2-methylbenzamide (1.4 g) was dissolved in dry THF (15 mL) under nitrogen, then Me2S.BH3 (94%, 1.34 mL) was added slowly. After stirred at room temperature for 1 h, the mixture was heated to 50° C. overnight. When 3-bromo-2-methylbenzamide disappeared, methanol was added dropwise until there was no more air bubble formed. Then 10 min later, 10% HCl was added dropwise, the mixture stirred for 1 h, and then solvent was removed. The white residual was recrystallized with iPrOH to obtain 1.1 g of the product. Yield: 35%. 1H NMR (400 MHz, DMSO-d6) δ 2.42 (s, 3H), 4.09 (s, 2H), 7.20 (t, J=7.8 Hz, 1H), 7.44 (d, J1=8.0 Hz, 1H), 7.63 (d, J1=7.6 Hz, 1H), 8.49 (br, 3H); 13C NMR (100 MHz, DMSO-d6) δ 18.8, 19.0, 46.1, 125.2, 127.4, 127.5, 129.0, 129.1, 132.1, 132.5, 134.7, 135.9, 136.1, 136.5; HPLC: retention time: 4.696 min; purity: 96.0%. BH3 (94%, 1.34 mL) was added slowly the mixture was heated to 50° C. overnight bubble formed the mixture stirred for 1 h solvent was removed The white residual was recrystallized with iPrOH

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

Procedure: 3-Bromo-2-methylbenzamide (1.4 g) was dissolved with dry THF (15 mL) under nitrogen, then Me2S.BH3 (94%, 1.34 mL) was added slowly. After being stirred at room temperature for 1 h, the mixture was heated to 50° C. overnight. When the 3-bromo-2-methylbenzamide disappeared, methanol was added dropwise until there no more air bubble formed. 10 min later, 10% HCl was added dropwise, stirred for 1 h, and then solvent was removed. The white residue was recrystallized with iPrOH to obtain 1.1 g of the product. Yield: 35%. 1H NMR (400 MHz, DMSO-d6): δ 2.42 (s, 3 H), 4.09 (s, 2 H), 7.20 (t, J=7.8 Hz, 1 H), 7.44 (d, J1=8.0 Hz, 1 H), 7.63 (d, J1=7.6 Hz, 1 H), 8.49 (br, 3 H); 13C NMR (100 MHz, DMSO-d6): δ 18.8, 19.0, 46.1, 125.2, 127.4, 127.5, 129.0, 129.1, 132.1, 132.5, 134.7, 135.9, 136.1, 136.5; HPLC: retention time: 4.696 min; purity: 96.0%. BH3 (94%, 1.34 mL) was added slowly the mixture was heated to 50° C. overnight bubble formed stirred for 1 h solvent was removed The white residue was recrystallized with iPrOH

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

Procedure: The title compound was prepared from 3-bromo-2-methylbenzamide (Ex IV-2) and 4-(1,3-dioxolan-2-yl)-3-(trifluoromethyl)phenylboronic acid (I-IX-8) according to the procedure described in Example IX-10, using PhMe/EtOH (4:1) as organic cosolvent. LC/MS (method A) 2.36 min; m/z 351 (M+H). LC/MS (method A) 2.36 min

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

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

Procedure: The title compound was prepared from 3-bromo-2-methylbenzamide (Ex IV-2) and 4-(1,3-dioxolan-2-yl)-3-(trifluoromethyl)phenylboronic acid (I-IX-8) according to the procedure described in Example IX-10, using PhMe/EtOH (4:1) as organic colsovent. LC/MS (method A) 2.36 min; m/z 351 (M+H). LC/MS (method A) 2.36 min