propylboronic acid

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: To a solution of 0.086 g (0.202 mmol) N-[(S)-(4-bromophenyl)(1-methyl-1H-1,2,3-triazol-4-yl)methyl]-2-(4-cyclopropylphenyl)acetamide in 1.0 ml THF was added 0.021 g (0.243 mmol) n-propylboronic acid, 0.017 g (0.020 mmol) PdCl2(dppf)-CH2Cl2 adduct, 0.084 g (0.607 mmol) solid potassium carbonate, and 0.117 g (0.607 mmol) Silver(I) oxide. The reaction mixture was irradiated in the microwave at 150° C. for 30 mins. The resulting solution was diluted with CH2Cl2, washed twice with water, dried over sodium sulfate, filtered, and concentrated in vacuo. Purification by preparative HPLC (5->95% CH3CN/H2O over 15 min, 0.05% added TFA, C18) to afford 0.024 g (30.6%) 2-(4-cyclopropylphenyl)-N-[(S)-(1-methyl-1H-1,2,3-triazol-4-yl)(4-propylphenyl)methyl]acetamide. 1H NMR (CDCl3, 400 MHz) 7.25 (m, 1H); 7.17-7.02 (m, 8H); 6.68 (d, J=8.24 Hz, 1H); 6.25 (d, J=7.78 Hz, 1H); 4.03 (s, 3H); 3.56 (s, 2H); 2.54 (t, J=7.42 Hz, 2H); 1.90-1.84 (m, 1H); 1.65-1.55-(m, 2H); 0.97-0.90 (m, 5H); 0.69-0.65 (m, 2H). HRMS (ES) [M+1]+ calcd for C24H28N4O: 389.2341. Found: 389.2343. The reaction mixture was irradiated in the microwave at 150° C. for 30 mins washed twice with water dried over sodium sulfate filtered concentrated in vacuo Purification by preparative HPLC (5->95% CH3CN/H2O over 15 min, 0.05% added TFA, C18)

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

Procedure: N-[(S)-(5-bromopyridin-2-yl)(1-methyl-1H-1,2,3-triazol-4-yl)methyl]-2-(4-isopropylphenyl)acetamide (0.075 g, 0.18 mmol) was mixed with n-propylboronic acid (0.04 g, 0.44 mmol), PdCl2(dppf)2 (0.014 g, 0.019 mmol), Ag2O (0.10 g, 0.44 mmol) and K2CO3 (0.073 g, 0.53 mmol) and degassed. THF (3 mL) was added and the mixture was heated in microwave at 130 C for 30 min. The reaction mixture was diluted with EtOAc and filtered through Celite. The solvent was removed and the residue was purified by reverse HPLC to give 2-(4-isopropylphenyl)-N-[(S)-(1-methyl-1H-1,2,3-triazol-4-yl)(5-propylpyridin-2-yl)methyl]acetamide (0.035 g, 51%). ES-MS [M+1]+: 430.1. 1H NMR (CDCl3, 400 MHz) δ 1H NMR (CDCl3, 400 MHz) δ 8.29 (d, J=2.0 Hz, 1H), 7.58 (d, J=6.4 Hz, 1H), 7.45 (dd, J=2.4, 8.0 Hz, 1H), 7.40 (s, 1H), 7.27 (d, J=8.0 Hz, 1H), 7.24-7.19 (ABq, 4H), 6.27 (d, J=7.2 Hz, 1H), 3.98 (s, 3H), 3.62 (s, 2H), 2.94-2.85 (m, J=6.8 Hz, 1H), 2.54 (t, J=7.6 Hz, 2 H), 1.66-1.56 (m, 2H), 1.24 (d, J=6.4 Hz, 6H), 0.93 (t, J=7.2 Hz, 3H). HRMS (ES) [M+1]+ calcd for C23H29N5O: 392.2445. Found: 392.2446. degassed THF (3 mL) was added the mixture was heated in microwave at 130 C for 30 min The reaction mixture was diluted with EtOAc filtered through Celite The solvent was removed the residue was purified by reverse HPLC

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

Procedure: N-[(S)-(5-bromopyridin-2-yl)(1-methyl-1H-1,2,3-triazol-4-yl)methyl]-2-(4-isopropylphenyl)acetamide (0.075 g, 0.18 mmol) was mixed with n-propylboronic acid (0.04 g, 0.44 mmol), PdCl2(dppf)2 (0.014 g, 0.019 mmol), Ag2O (0.10 g, 0.44 mmol) and K2CO3 (0.073 g, 0.53 mmol) and degassed. THF (3 mL) was added and the mixture was heated in microwave at 130 C for 30 min. The reaction mixture was diluted with EtOAc and filtered through Celite. The solvent was removed and the residue was purified by reverse HPLC to give 2-(4-isopropylphenyl)-N-[(S)-(1-methyl-1H-1,2,3-triazol-4-yl)(5-propylpyridin-2-yl)methyl]acetamide (0.035 g, 51%). ES-MS [M+1]+: 430.1. 1H NMR (CDCl3, 400 MHz) δ 1H NMR (CDCl3, 400 MHz) δ 8.29 (d, J=2.0 Hz, 1H), 7.58 (d, J=6.4 Hz, 1H), 7.45 (dd, J=2.4, 8.0 Hz, 1H), 7.40 (s, 1H), 7.27 (d, J=8.0 Hz, 1H), 7.24-7.19 (ABq, 4H), 6.27 (d, J=7.2 Hz, 1H), 3.98 (s, 3H), 3.62 (s, 2H), 2.94-2.85 (m, J=6.8 Hz, 1H), 2.54 (t, J=7.6 Hz, 2 H), 1.66-1.56 (m, 2H), 1.24 (d, J=6.4 Hz, 6H), 0.93 (t, J=7.2 Hz, 3H). HRMS (ES) [M+1]+ calcd for C23H29N5O: 392.2445. Found: 392.2446. degassed THF (3 mL) was added the mixture was heated in microwave at 130 C for 30 min The reaction mixture was diluted with EtOAc filtered through Celite The solvent was removed the residue was purified by reverse HPLC

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

Procedure: The preparation was performed in a similar manner as Reference Example 1.13 (d) from ethyl 6-chloro-3-methylpyrazine-2-carboxylate (Reference Example 1.13 (c)) (1.50 g, 7.48 mmol) and n-propylboronic acid (1.32 g, 15.0 mmol) to give ethyl 3-methyl-6-propylpyrazine-2-carboxylate. MS (APCI): m/z 209 (M+H).

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

Procedure: The preparation was performed in a similar manner as Reference Example 1.13 (d) from ethyl 6-chloro-3-methylpyrazine-2-carboxylate (Reference Example 1.13 (c)) (1.50 g, 7.48 mmol) and n-propylboronic acid (1.32 g, 15.0 mmol) to give ethyl 3-methyl-6-propylpyrazine-2-carboxylate. MS (APCI): m/z 209 (M+H).

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

Procedure: The compound was synthesized as in Example 3.1 using 4-bromobenzaldehyde (250 mg, 1.35 mmol) in place of 5-bromo-2-formylfuran and propylboronic acid (196 mg, 2.23 mmol) in place of hexylboronic acid to give 4-propylbenzaldehyde (58 mg, 29%). Used without further characterization.

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

Procedure: The compound was synthesized as in Example 3.1 using 4-bromobenzaldehyde (250 mg, 1.35 mmol) in place of 5-bromo-2-formylfuran and propylboronic acid (196 mg, 2.23 mmol) in place of hexylboronic acid to give 4-propylbenzaldehyde (58 mg, 29%). Used without further characterization.

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

Procedure: The compound was synthesized as in Example 3.1 using 5-bromothiophene-2-carbaldehyde (250 mg, 1.31 mmol) in place of 5-bromo-2-formylfuran and propylboronic acid (190 mg, 2.16 mmol) in place of hexylboronic acid to give 5-propylthiophene-2-carbaldehyde (58 mg, 29%). Used without further characterization.

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

Procedure: The title compound was prepared in analogy to example 3, using N-[2-(3-bromo-4-fluoro-phenyl)-ethyl]-N-(4-tert-butyl-benzyl)-3-chloro-2-fluoro-5-trifluoromethyl-benzamide (Example B178) and n-propylboronic acid. 552.2 [ISP (M+H)+]

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

Procedure: The title compound was prepared in analogy to example 3, using 3-bromo-N-(4-tert-butyl-benzyl)-5-chloro-N-[2-(3-fluoro-5-trifluoromethyl-phenyl)-ethyl]-benzamide (Example B177) and n-propylboronic acid. 534.3 [ISP (M+H)+]