3-Bromo-6-(cyclopropyl)pyridine

2-Cyclopropyl-5-('4, 4, 5, 5-tetramethyl-L3.2-dioxaborolan-2-vDpyridine0.5M Zinc chloride in THF (5.5 mL, 2.8 mmol) was added to a solution of 0.5M cyclopropylmagnesium bromide in THF (5.5 mL, 2.8 mmol) under argon. The solution was stirred at RT for 2 h at which time a slurry had formed. To this slurry was added in one portion 2, 5-dibromopyridine (0.65 g, 2.8 mmol) and PdClTo a solution 2, 5-dibromopyridine[CAS 624-28-2, commercially available](5 g, 21 mmol) and Pd(PPh2-Cyclopropyl-5-('4, 4, 5, 5-tetramethyl-L3.2-dioxaborolan-2-vDpyridine0.5M Zinc chloride in THF (5.5 mL, 2.8 mmol) was added to a solution of 0.5M cyclopropylmagnesium bromide in THF (5.5 mL, 2.8 mmol) under argon. The solution was stirred at RT for 2 h at which time a slurry had formed. To this slurry was added in one portion 2, 5-dibromopyridine (0.65 g, 2.8 mmol) and PdClTo a solution 2, 5-dibromopyridine[CAS 624-28-2, commercially available](5 g, 21 mmol) and Pd(PPhGeneral procedure: EXAMPLES 74 TO 119 (GENERAL METHOD 4) The appropriate aniline and the appropriate aryl halide were dissolved in a solvent, and a base (3 equiv.) was added. The solution was degassed, then a transition metal catalyst (0.05 equiv.) and a phosphine ligand (0.10 equiv.) were added. The reaction mixture was heated at 80C for 3 h, or until the reaction was complete. The solution was filtered, and the material was isolated using silica gel chromatography or reverse phase HPLC, then deprotected in accordance with General Method 2, to afford the title compounds. As necessary, final products were further purified by preparative reverse phase HPLC and isolated as the TFA salt. EXAMPLES 120 TO 158 (0688) The compounds identified in the following Table were prepared from the appropriate aniline and the appropriate aryl halide in accordance with General Method 4. (0689) The solvent employed for Examples 120-158 was l, 4-dioxane. (0690) The base employed for Examples 120-141 and 143-158 was K3PO4. The base employed for Example 142 was sodium te/t-butoxidc. The transition metal catalyst employed for Examples 120-125, 127-132 and 134- 158 was BrettPhos Pd G3. The transition metal catalyst employed for Example 126 was BrettPhos Pd Gl . The transition metal catalyst employed for Example 133 was Pd2(dba)3. (0691) The phosphine ligand employed for Examples 120-132, 134-149 and 151-158 was BrettPhos. The phosphine ligand employed for Example 133 was XPhos. The phosphine ligand employed for Example 150 was XantPhos. (0692) (0693) * Method 4General procedure: The appropriate aryl halide and the appropriate aniline were dissolved in 1, 4 dioxane, and K3PO4 (3 equiv.) was added. The solution was degassed, then a transition metal catalyst (0.05 equiv.) and a phosphine ligand (0.10 equiv.) were added. The reaction mixture was heated at 80C for 3 h or until the reaction was complete. The solution was filtered. The material was isolated using silica gel chromatography or reverse phase HPLC, then deprotected in accordance with General Method 2. As necessary, the material was further purified by preparative reverse phase HPLC. The resulting solid was dissolved in DCM, and 4M HC1 in l, 4-dioxane (6 equiv.) was added. The mixture was stirred for 30 minutes. The solvent was removed under reduced pressure, and the title compound (HC1 salt) was isolated after trituration with diethyl ether or DCM/pentane.To a 5-L, 4-necked round-bottom flask purged and maintained with an inert atmosphere of 42 nitrogen was charged with a solution of 81 Mg (200 g, 8.33 mol, 10.00 eq.) in 45 tetrahydrofuran (1500 mL), 82 I2 (1 g) and 83 bromocyclopropane (400 g, 3.33 mol, 4.00 eq.). The reaction mixture was stirred for 3 h at 65 C. and then was added to a solution of 84 ZnCl2 (560 g, 4.12 mol, 5.00 equiv.) in tetrahydrofuran (2000 mL) at 10 C. The resulting solution was stirred for 2 h at RT and then Pd(dppf)Cl2 (20 g), 85 2, 5-dibromopyridine (200 g, 843.88 mmol, 1.00 equiv) was added. The reaction mixture was allowed to stir overnight at RT and was quenched by the addition of 500 mL of 86 water. The resulting mixture was concentrated under vacuum and then extracted with 3×5 L of ethyl acetate. The combined organic layer was dried over anhydrous sodium sulfate and concentrated under vacuum. The residue was purified by a silica gel column with EtOAc/petroleum ether (1/2) to give 87 To a solution of urea compound with hydrogen petroleum etherroxide (1:1) (1140 mg, 12.12 mmol) in DCM (10 mL) was added TFAA (2545 mg, 12.12 mmol). The reaction mixture was stirred at 0 C for 20 mi To a 3-L, 4-necked round-bottom flask was charged with a solution of 87 2-Cyclopropyl-5-('4, 4, 5, 5-tetramethyl-L3.2-dioxaborolan-2-vDpyridine0.5M Zinc chloride in THF (5.5 mL, 2.8 mmol) was added to a solution of 0.5M cyclopropylmagnesium bromide in THF (5.5 mL, 2.8 mmol) under argon. The solution was stirred at RT for 2 h at which time a slurry had formed. To this slurry was added in one portion 2, 5-dibromopyridine (0.65 g, 2.8 mmol) and PdCl2 x dppf (0.041 g, 0.050 mmol). After a few minutes an exotherm was seen and the slurry became thicker, the exotherm subsided and the slurry was stirred at RT overnight. The reaction mixture was poured into saturated sodium bicarbonate solution and extracted with ether. The ether phase was dried, filtered and concentrated, then re-dissolved in DCM and applied to a short plug of silica gel. The gel was washed with DCM and the washings were concentrated. The residue was taken up in ether and washed with 1.0M hydrochloric acid. The acidic water phase was made basic with 2.0M sodium hydroxide and the product was extracted back into ether. The combined ether phases were washed with brine, dried, filtered and concentrated to give 0.28 g (50%) of

Molecular Weight:198.06
XLogP3:2.1
Hydrogen Bond Acceptor Count:1
Rotatable Bond Count:1
Exact Mass:196.98401
Monoisotopic Mass:196.98401
Topological Polar Surface Area:12.9
Heavy Atom Count:10
Complexity:122
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes