[(E)-oct-1-enyl]boronic acid

Conditions: temp:65.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To anhydrous THF (20 ml) containing 64 (0.49 g, 2.17 mmol) (see Scheme 13), were added 1.5 eq of (E)-octene-1-ylboronic acid (0.51 g). The resulting mixture was stirred for 2 hours under N2. Successively were added 2 eq of K3PO4 (0.92 g), 2 mol % of Pd(OAc)2 (10 mg) and 4 mol % of S-Phos (36 mg). After the addition, the resulting solution was warmed at 65° C. for 18 hours under N2. After cooling to room temperature, the mixture was diluted with ethyl acetate, washed with a saturated NaHCO3 solution, dried (Na2SO4), filtered and concentrated. The resulting residue was purified by flash chromatography (diethyl ether/PE 1/1) to afford 3-(4-Oct-1-enyl-isoxazol-3-yl)-pyridine (compound 67B) as an oil (0.19 g, 34%). 1H-NMR (400 MHz, CDCl3): δ 8.9 (d, J=2 Hz, 1H), 8.72 (dd, J=5 Hz, 2 Hz, 1H), 8.49 (s, 1H), 7.9 (dt, J=8 Hz, 2 Hz, 1H), 7.45-7.40 (m, 1H), 6.11-5.99 (m, 2H), 2.21-2.13 (m, 2H), 1.46-1.38 (m, 2H), 1.37-1.21 (m, 6H), 0.91 (t, J=7 Hz, 3H). After the addition After cooling to room temperature washed with a saturated NaHCO3 solution dried (Na2SO4) filtered concentrated The resulting residue was purified by flash chromatography (diethyl ether/PE 1/1)

Conditions: temp:90.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To toluene (20 ml) containing 36A (0.91 g, 2.5 mmol) (see Scheme 7), was added 1.5 eq (E)-octene-1-ylboronic acid (0.59 g). The resulting mixture was stirred for 2 hours under N2. Successively were added 2 eq of K3PO4 (1.06 g), 4 mol % of Pd(OAc)2 (22.4 mg) and 8 mol % of S-Phos (82 mg). After the addition, the resulting solution was warmed at 90° C. for 18 hours under N2. After cooling to room temperature, the mixture was diluted with ethyl acetate, washed three times with a saturated NaHCO3 solution, dried (Na2SO4), filtered and concentrated. The resulting residue was purified by flash chromatography (diethyl ether/PE 1/1) to afford 3-(1-phenylsulfonyl-4-oct-1-enyl-1H-pyrazol-3-yl)-pyridine (46C) as an oil (0.31 g, 32%). 1H-NMR (400 MHz, CDCl3): δ 8.85 (d, J=2 Hz, 1H), 8.65 (dd, J=5 Hz, 2 Hz, 1H), 8.15 (s, 1H), 8.08-8.05 (m, 2H), 7.93 (dt, J=8 Hz, 2 Hz, 1H), 7.69-7.64 (m, 1H), 7.59-7.52 (m, 2H), 7.37-7.33 (m, 1H), 6.19 (d, J=16 Hz, 1H), 6.10-6.03 (m, 1H), 2.19-2.12 (m, 2H), 1.45-1.37 (m, 2H), 1.36-1.23 (m, 6H), 0.90 (t, J=7 Hz, 3H). After the addition After cooling to room temperature washed three times with a saturated NaHCO3 solution dried (Na2SO4) filtered concentrated The resulting residue was purified by flash chromatography (diethyl ether/PE 1/1)

Conditions: temp:65.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To anhydrous THF (20 ml) containing 64 (0.49 g, 2.17 mmol) (see Scheme 13), were added 1.5 eq of (E)-octene-1-ylboronic acid (0.51 g). The resulting mixture was stirred for 2 hours under N2. Successively were added 2 eq of K3PO4 (0.92 g), 2 mol % of Pd(OAc)2 (10 mg) and 4 mol % of S-Phos (36 mg). After the addition, the resulting solution was warmed at 65° C. for 18 hours under N2. After cooling to room temperature, the mixture was diluted with ethyl acetate, washed with a saturated NaHCO3 solution, dried (Na2SO4), filtered and concentrated. The resulting residue was purified by flash chromatography (diethyl ether/PE 1/1) to afford 3-(4 Oct-1-enyl-isoxazol-3-yl)-pyridine (compound 67B) as an oil (0.19 g, 34%). 1H-NMR (400 MHz, CDCl3): δ 8.9 (d, J=2 Hz, 1H), 8.72 (dd, J=5 Hz, 2 Hz, 1H), 8.49 (s, 1H), 7.9 (dt, J=8 Hz, 2 Hz, 1H), 7.45-7.40 (m, 1H), 6.11-5.99 (m, 2H), 2.21-2.13 (m, 2H), 1.46-1.38 (m, 2H), 1.37-1.21 (m, 6H), 0.91 (t, J=7 Hz, 3H). After the addition After cooling to room temperature washed with a saturated NaHCO3 solution dried (Na2SO4) filtered concentrated The resulting residue was purified by flash chromatography (diethyl ether/PE 1/1)

Conditions: temp:65.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To anhydrous THF (20 ml) containing 64 (0.49 g, 2.17 mmol) (see Scheme 13), were added 1.5 eq of (E)-octene-1-ylboronic acid (0.51 g). The resulting mixture was stirred for 2 hours under N2. Successively were added 2 eq of K3PO4 (0.92 g), 2 mol % of Pd(OAc)2 (10 mg) and 4 mol % of S-Phos (36 mg). After the addition, the resulting solution was warmed at 65° C. for 18 hours under N2. After cooling to room temperature, the mixture was diluted with ethyl acetate, washed with a saturated NaHCO3 solution, dried (Na2SO4), filtered and concentrated. The resulting residue was purified by flash chromatography (diethyl ether/PE 1/1) to afford 3-(4 Oct-1-enyl-isoxazol-3-yl)-pyridine (compound 67B) as an oil (0.19 g, 34%). 1H-NMR (400 MHz, CDCl3): δ 8.9 (d, J=2 Hz, 1H), 8.72 (dd, J=5 Hz, 2 Hz, 1H), 8.49 (s, 1H), 7.9 (dt, J=8 Hz, 2 Hz, 1H), 7.45-7.40 (m, 1H), 6.11-5.99 (m, 2H), 2.21-2.13 (m, 2H), 1.46-1.38 (m, 2H), 1.37-1.21 (m, 6H), 0.91 (t, J=7 Hz, 3H). After the addition After cooling to room temperature washed with a saturated NaHCO3 solution dried (Na2SO4) filtered concentrated The resulting residue was purified by flash chromatography (diethyl ether/PE 1/1)

Conditions: temp:90.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To toluene (20 ml) containing 36A (0.91 g, 2.5 mmol) (see Scheme 7), was added 1.5 eq (E)-octene-1-ylboronic acid (0.59 g). The resulting mixture was stirred for 2 hours under N2. Successively were added 2 eq of K3PO4 (1.06 g), 4 mol % of Pd(OAc)2 (22.4 mg) and 8 mol % of S-Phos (82 mg). After the addition, the resulting solution was warmed at 90° C. for 18 hours under N2. After cooling to room temperature, the mixture was diluted with ethyl acetate, washed three times with a saturated NaHCO3 solution, dried (Na2SO4), filtered and concentrated. The resulting residue was purified by flash chromatography (diethyl ether/PE 1/1) to afford 3-(1-phenylsulfonyl-4-oct-1-enyl-1H-pyrazol-3-yl)-pyridine (46C) as an oil (0.31 g, 32%). 1H-NMR (400 MHz, CDCl3): δ 8.85 (d, J=2 Hz, 1H), 8.65 (dd, J=5 Hz, 2 Hz, 1H), 8.15 (s, 1H), 8.08-8.05 (m, 2H), 7.93 (dt, J=8 Hz, 2 Hz, 1H), 7.69-7.64 (m, 1H), 7.59-7.52 (m, 2H), 7.37-7.33 (m, 1H), 6.19 (d, J=16 Hz, 1H), 6.10-6.03 (m, 1H), 2.19-2.12 (m, 2H), 1.45-1.37 (m, 2H), 1.36-1.23 (m, 6H), 0.90 (t, J=7 Hz, 3H). After the addition After cooling to room temperature washed three times with a saturated NaHCO3 solution dried (Na2SO4) filtered concentrated The resulting residue was purified by flash chromatography (diethyl ether/PE 1/1)

Conditions: temp:90.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To toluene (20 ml) containing 36A (0.91 g, 2.5 mmol) (see Scheme 7), was added 1.5 eq (E)-octene-1-ylboronic acid (0.59 g). The resulting mixture was stirred for 2 hours under N2. Successively were added 2 eq of K3PO4 (1.06 g), 4 mol % of Pd(OAc)2 (22.4 mg) and 8 mol % of S-Phos (82 mg). After the addition, the resulting solution was warmed at 90° C. for 18 hours under N2. After cooling to room temperature, the mixture was diluted with ethyl acetate, washed three times with a saturated NaHCO3 solution, dried (Na2SO4), filtered and concentrated. The resulting residue was purified by flash chromatography (diethyl ether/PE 1/1) to afford 3-(1-phenylsulfonyl-4-oct-1-enyl-1H-pyrazol-3-yl)-pyridine (46C) as an oil (0.31 g, 32%). 1H-NMR (400 MHz, CDCl3): δ 8.85 (d, J=2 Hz, 1H), 8.65 (dd, J=5 Hz, 2 Hz, 1H), 8.15 (s, 1H), 8.08-8.05 (m, 2H), 7.93 (dt, J=8 Hz, 2 Hz, 1H), 7.69-7.64 (m, 1H), 7.59-7.52 (m, 2H), 7.37-7.33 (m, 1H), 6.19 (d, J=16 Hz, 1H), 6.10-6.03 (m, 1H), 2.19-2.12 (m, 2H), 1.45-1.37 (m, 2H), 1.36-1.23 (m, 6H), 0.90 (t, J=7 Hz, 3H). After the addition After cooling to room temperature washed three times with a saturated NaHCO3 solution dried (Na2SO4) filtered concentrated The resulting residue was purified by flash chromatography (diethyl ether/PE 1/1)

Conditions: temp:65.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To anhydrous THF (20 ml) containing 64 (0.49 g, 2.17 mmol) (see Scheme 13), were added 1.5 eq of (E)-octene-1-ylboronic acid (0.51 g). The resulting mixture was stirred for 2 hours under N2. Successively were added 2 eq of K3PO4 (0.92 g), 2 mol % of Pd(OAc)2 (10 mg) and 4 mol % of S-Phos (36 mg). After the addition, the resulting solution was warmed at 65° C. for 18 hours under N2. After cooling to room temperature, the mixture was diluted with ethyl acetate, washed with a saturated NaHCO3 solution, dried (Na2SO4), filtered and concentrated. The resulting residue was purified by flash chromatography (diethyl ether/PE 1/1) to afford 3-(4-Oct-1-enyl-isoxazol-3-yl)-pyridine (compound 67B) as an oil (0.19 g, 34%). 1H-NMR (400 MHz, CDCl3): δ 8.9 (d, J=2 Hz, 1H), 8.72 (dd, J=5 Hz, 2 Hz, 1H), 8.49 (s, 1H), 7.9 (dt, J=8 Hz, 2 Hz, 1H), 7.45-7.40 (m, 1H), 6.11-5.99 (m, 2H), 2.21-2.13 (m, 2H), 1.46-1.38 (m, 2H), 1.37-1.21 (m, 6H), 0.91 (t, J=7 Hz, 3H). After the addition After cooling to room temperature washed with a saturated NaHCO3 solution dried (Na2SO4) filtered concentrated The resulting residue was purified by flash chromatography (diethyl ether/PE 1/1)

Conditions: temp:90.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To toluene (20 ml) containing 36A (0.91 g, 2.5 mmol) (see Scheme 7), was added 1.5 eq (E)-octene-1-ylboronic acid (0.59 g). The resulting mixture was stirred for 2 hours under N2. Successively were added 2 eq of K3PO4 (1.06 g), 4 mol % of Pd(OAc)2 (22.4 mg) and 8 mol % of S-Phos (82 mg). After the addition, the resulting solution was warmed at 90° C. for 18 hours under N2. After cooling to room temperature, the mixture was diluted with ethyl acetate, washed three times with a saturated NaHCO3 solution, dried (Na2SO4), filtered and concentrated. The resulting residue was purified by flash chromatography (diethyl ether/PE 1/1) to afford 3-(1-phenylsulfonyl-4-oct-1-enyl-1H-pyrazol-3-yl)-pyridine (46C) as an oil (0.31 g, 32%). 1H-NMR (400 MHz, CDCl3): δ 8.85 (d, J=2 Hz, 1H), 8.65 (dd, J=5 Hz, 2 Hz, 1H), 8.15 (s, 1H), 8.08-8.05 (m, 2H), 7.93 (dt, J=8 Hz, 2 Hz, 1H), 7.69-7.64 (m, 1H), 7.59-7.52 (m, 2H), 7.37-7.33 (m, 1H), 6.19 (d, J=16 Hz, 1H), 6.10-6.03 (m, 1H), 2.19-2.12 (m, 2H), 1.45-1.37 (m, 2H), 1.36-1.23 (m, 6H), 0.90 (t, J=7 Hz, 3H). After the addition After cooling to room temperature washed three times with a saturated NaHCO3 solution dried (Na2SO4) filtered concentrated The resulting residue was purified by flash chromatography (diethyl ether/PE 1/1)

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

Procedure: 5-{3-[2-(4-Bromo-benzyl)-4-(2,4-dichloro-phenyl)-imidazol-1-yl]-phenyl}-1,2,5-thiadiazolidine-3-one-1,1-dioxide (59 mg, 0.1 mmol) was treated as described in general procedure G using trans-1-octen-1-ylboronic acid (47 mg, 0.3 mmol) to give 5-{3-[4-(2,4-dichloro-phenyl)-2-(4-oct-1-enyl-benzyl)-imidazol-1-yl]-phenyl}-1,2,5-thiadiazolidine-3-one-1,1-dioxide.

Conditions: temp:65.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To anhydrous THF (20 ml) containing 64 (0.49 g, 2.17 mmol) (see Scheme 13), were added 1.5 eq of (E)-octene-1-ylboronic acid (0.51 g). The resulting mixture was stirred for 2 hours under N2. Successively were added 2 eq of K3PO4 (0.92 g), 2 mol % of Pd(OAc)2 (10 mg) and 4 mol % of S-Phos (36 mg). After the addition, the resulting solution was warmed at 65° C. for 18 hours under N2. After cooling to room temperature, the mixture was diluted with ethyl acetate, washed with a saturated NaHCO3 solution, dried (Na2SO4), filtered and concentrated. The resulting residue was purified by flash chromatography (diethyl ether/PE 1/1) to afford 3-(4-Oct-1-enyl-isoxazol-3-yl)-pyridine (compound 67B) as an oil (0.19 g, 34%). 1H-NMR (400 MHz, CDCl3): δ 8.9 (d, J=2 Hz, 1H), 8.72 (dd, J=5 Hz, 2 Hz, 1H), 8.49 (s, 1H), 7.9 (dt, J=8 Hz, 2 Hz, 1H), 7.45-7.40 (m, 1H), 6.11-5.99 (m, 2H), 2.21-2.13 (m, 2H), 1.46-1.38 (m, 2H), 1.37-1.21 (m, 6H), 0.91 (t, J=7 Hz, 3H). After the addition After cooling to room temperature washed with a saturated NaHCO3 solution dried (Na2SO4) filtered concentrated The resulting residue was purified by flash chromatography (diethyl ether/PE 1/1)

Conditions: temp:90.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To toluene (20 ml) containing 36A (0.91 g, 2.5 mmol) (see Scheme 7), was added 1.5 eq (E)-octene-1-ylboronic acid (0.59 g). The resulting mixture was stirred for 2 hours under N2. Successively were added 2 eq of K3PO4 (1.06 g), 4 mol % of Pd(OAc)2 (22.4 mg) and 8 mol % of S-Phos (82 mg). After the addition, the resulting solution was warmed at 90° C. for 18 hours under N2. After cooling to room temperature, the mixture was diluted with ethyl acetate, washed three times with a saturated NaHCO3 solution, dried (Na2SO4), filtered and concentrated. The resulting residue was purified by flash chromatography (diethyl ether/PE 1/1) to afford 3-(1-phenylsulfonyl-4-oct-1-enyl-1H-pyrazol-3-yl)-pyridine (46C) as an oil (0.31 g, 32%). 1H-NMR (400 MHz, CDCl3): δ 8.85 (d, J=2 Hz, 1H), 8.65 (dd, J=5 Hz, 2 Hz, 1H), 8.15 (s, 1H), 8.08-8.05 (m, 2H), 7.93 (dt, J=8 Hz, 2 Hz, 1H), 7.69-7.64 (m, 1H), 7.59-7.52 (m, 2H), 7.37-7.33 (m, 1H), 6.19 (d, J=16 Hz, 1H), 6.10-6.03 (m, 1H), 2.19-2.12 (m, 2H), 1.45-1.37 (m, 2H), 1.36-1.23 (m, 6H), 0.90 (t, J=7 Hz, 3H). After the addition After cooling to room temperature washed three times with a saturated NaHCO3 solution dried (Na2SO4) filtered concentrated The resulting residue was purified by flash chromatography (diethyl ether/PE 1/1)

Conditions: temp:65.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To anhydrous THF (20 ml) containing 64 (0.49 g, 2.17 mmol) (see Scheme 13), were added 1.5 eq of (E)-octene-1-ylboronic acid (0.51 g). The resulting mixture was stirred for 2 hours under N2. Successively were added 2 eq of K3PO4 (0.92 g), 2 mol % of Pd(OAc)2 (10 mg) and 4 mol % of S-Phos (36 mg). After the addition, the resulting solution was warmed at 65° C. for 18 hours under N2. After cooling to room temperature, the mixture was diluted with ethyl acetate, washed with a saturated NaHCO3 solution, dried (Na2SO4), filtered and concentrated. The resulting residue was purified by flash chromatography (diethyl ether/PE 1/1) to afford 3-(4 Oct-1-enyl-isoxazol-3-yl)-pyridine (compound 67B) as an oil (0.19 g, 34%). 1H-NMR (400 MHz, CDCl3): δ 8.9 (d, J=2 Hz, 1H), 8.72 (dd, J=5 Hz, 2 Hz, 1H), 8.49 (s, 1H), 7.9 (dt, J=8 Hz, 2 Hz, 1H), 7.45-7.40 (m, 1H), 6.11-5.99 (m, 2H), 2.21-2.13 (m, 2H), 1.46-1.38 (m, 2H), 1.37-1.21 (m, 6H), 0.91 (t, J=7 Hz, 3H). After the addition After cooling to room temperature washed with a saturated NaHCO3 solution dried (Na2SO4) filtered concentrated The resulting residue was purified by flash chromatography (diethyl ether/PE 1/1)