(2,3-dichlorophenyl)boronic 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:

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 title compound was prepared as described in Example 76, STEP B, substituting 4-iodoaniline and 2,3-dichlorophenylboronic acid for 4-bromo-3-methylaniline and 4-chlorophenylboronic acid.

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

Procedure: A mixture of 2,3-dichlorophenylboronic acid (279 mg, 1.464 mmol), methyl 2-(5-bromopyridin-3-yl)cyclopropanecarboxylate (357 mg, 1.394 mmol), PdCl2(dppf).CH2Cl2 adduct (114 mg, 0.139 mmol) and Na2CO3 (2 M in water, 1.743 ml, 3.49 mmol) in DMF (7 ml) was heated at 100° C. under nitrogen atmosphere. After 1 h, the solvent was removed under vacuo. The residue was purified by flash column (EtOAc/Heptane=0-25%, v/v) to give methyl 2-(5-(2,3-dichlorophenyl)pyridin-3-yl)cyclopropanecarboxylate (335 mg, 1.040 mmol, 74% yield). ESI-MS m/z: 322 [M+1]+; 1H NMR (CDCl3, 400 MHz) 1.38-1.41 (m, 1H), 1.68-1.73 (m, 1H), 1.97-2.01 (m, 1H), 2.58-2.63 (m, 1H), 3.75 (s, 3H), 7.21 (dd, J=7.6, 1.2 Hz, 1H), 7.30 (t, J=7.6 Hz, 1H), 7.43 (bs, 1H), 7.53 (dd, J=7.6, 1.2 Hz, 1H), 8.48 (d, J=1.6 Hz, 1H), 8.50 (d, J=1.6 Hz, 1H), the solvent was removed under vacuo The residue was purified by flash column (EtOAc/Heptane=0-25%, v/v)

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

Procedure: A mixture of 3-(5-bromo-pyridin-3-yl)-propionic acid methyl ester (155 mg), 2,3-dichlorobenzeneboronic acid (142 mg, 0.744 mmol), PdCl2(dppf).CH2Cl2 adduct (48.6 mg, 0.059 mmol) and Na2CO3 (2 M, 0.929 ml, 1.859 mmol) in DMF (5 ml) was heated at 100° C. After 40 min, solvent was removed in vacuo. The residue was purified via flash column (EtOAc/Heptane=0-20-25%, v/v) to give 3-[5-(2,3-Dichloro-phenyl)-pyridin-3-yl]-propionic acid methyl ester (101 mg, 0.326 mmol, 43% yield). ESI-MS m/z: 310[M+1]+; 1H NMR (CDCl3, 400 MHz) δ 2.71 (t, J=7.6 Hz, 2H), 3.05 (t, J=7.6 Hz, 2H), 3.70 (s, 3H), 7.23 (dd, J=7.6, 1.6 Hz, 1H), 7.30 (t, J=7.6 Hz, 1H), 7.53 (dd, J=7.6, 1.6 Hz, 1H), 7.63 (s, 1H), 8.52 (s, 2H). solvent was removed in vacuo The residue was purified via flash column (EtOAc/Heptane=0-20-25%, v/v)

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

Procedure: A solution of 3,5-dibromo-4-amino-pyridine 1 (4.0 g, 15.87 mmol), Pd(PPh3)4 (0.91 g, 0.78 mmol) and aqueous solution of Na2CO3 (23.8 ml, 2M ) in toluene (80 ml ) is added to a solution of dichlorobenzene boronic acid (6.23 g, 46.4 mmole) in ethanol (24 ml). The mixture is refluxed for 14 h., diluted with ethyl acetate and washed with saturated NH4Cl solution. The organic layer is dried over sodium sulfate and concentrated in vacuo. The residue is chromatographed on silica gel to give 2. The mixture is refluxed for 14 h. washed with saturated NH4Cl solution The organic layer is dried over sodium sulfate concentrated in vacuo The residue is chromatographed on silica gel to give 2

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

Procedure: A solution of 3,5-dibromo-4-amino-pyridine 1 (4.0 g, 15.87 mmol), Pd(PPh3)4 (0.91 g, 0.78 mmol) and aqueous solution of Na2CO3 (23.8 ml, 2M ) in toluene (80 ml ) is added to a solution of dichlorobenzene boronic acid (6.23 g, 46.4 mmole) in ethanol (24 ml). The mixture is refluxed for 14 h., diluted with ethyl acetate and washed with saturated NH4Cl solution. The organic layer is dried over sodium sulfate and concentrated in vacuo. The residue is chromatographed on silica gel to give 2. The mixture is refluxed for 14 h. washed with saturated NH4Cl solution The organic layer is dried over sodium sulfate concentrated in vacuo The residue is chromatographed on silica gel to give 2

Conditions: temp:80.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a suspension of 3-bromopyridine-2,6-diamine (0.376 g, 2.00 mmol) in 1,4-dioxane (12 ml) and water (6 ml) was added 2,3-dichlorophenyl boronic acid (0.573 g, 3.00 mmol), potassium carbonate (0.552 g, 4.00 mmol) and palladium tetrakis(triphenylphosphine) (0.115 g, 0.01 mmol). The reaction was purged with nitrogen and heated at 80° C. for 18 hours. Further palladium tetrakis(triphenylphosphine) (0.115 g, 0.01 mmol) and 2,3-dichlorophenyl boronic acid (0.573 g, 3.00 mmol) were added and the reaction heated at 80° C. for a further 18 hours before concentrating in vacuo. The residue was taken up in ethyl acetate (20 ml) and washed with a saturated aqueous solution of K2CO3 before drying over MgSO4 and concentrating in vacuo. The residue was purified by silica gel column chromatography, eluting with 99:1 dichloromethane:methanol, then recrystallised from toluene to afford the title compound (0.180 g, 35% yield). The reaction was purged with nitrogen the reaction heated at 80° C. for a further 18 hours before concentrating in vacuo washed with a saturated aqueous solution of K2CO3 before drying over MgSO4 concentrating in vacuo The residue was purified by silica gel column chromatography eluting with 99:1 dichloromethane methanol, then recrystallised from toluene

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

Procedure: A 15 mL round bottom flask was charged with (+)-(4aR)-(10bR)-4-methyl-8-bromo-10b-methyl-1,2,3,4,4a,5,6,10b-octahydrobenzo[f]quinolin-3-one (200 mg, 0.65 mmol), tetrakis (triphenylphosphine) palladium (0) (23 mg, 0.02 mmol), 2,3-dichlorophenylboronic acid (187 mg, 0.98 mmol), 0.65 mL of 2M sodium carbonate solution and 2 mL of THF, fitted with a reflux condenser, and the stirred mixture was heated at 80°, under nitrogen, for 16 h. The mixture was cooled, diluted with chloroform (50 mL) and washed with brine (2×50 mL). The combined organic extracts were dried over sodium sulfate, concentrated, and purified by silica gel chromatography (ethyl acetate eluent), to give 193 mg (79%) of the title compound as an off-white solid. mp 131°-134° FDMS: m/e=373 α[D]589 =+81.02 (c=1.05, chloroform). fitted with a reflux condenser the stirred mixture was heated at 80°, under nitrogen, for 16 h The mixture was cooled washed with brine (2×50 mL) The combined organic extracts were dried over sodium sulfate concentrated purified by silica gel chromatography (ethyl acetate eluent)