6-Bromo-1H-pyrrolo[3,2-c]pyridine

6-Bromo-1H-pyrrolo[2, 3-b]pyridine (4 g, 20.3 mmol) was dissolved in 1, 4-dioxane (100 mL) and DIPEA (11 mL, 63.1 mmol) added followed by triisopropylsilyl trifluromethanesulfonate (6.5 mL, 24 mmol). The reaction mixture was then stirred at r.t. for 30 min. before it was heated at 80C overnight. Triisopropylsilyl trifluromethanesulfonate (1.2 equiv., 24.4 mmol) was added and stirred at 80C for an additional 3 hours. The reaction was cooled down to ambient temperature and NH4Cl aq. solution and EtOAc were added. The layers were separated and the aq. phase was extracted with EtOAc. The combined organic layers were dried over MgSO4 and the solvent was removed under vacuum. The residue was purified by flash chromatography using gradient elution from hexane to a 1:1 mixture hexane:EtOAc to yield Intermediate 8 (5.2 g, 72% yield).General procedure: The appropriate heterocycle (1 equiv.) was dissolved in a mixture of DMF and THF (1:1 or 1:1.5 respectively, 0.2 M). The solution was cooled to 0 C and sodium hydride (1.2 or 2.2 equiv.) carefully added portion wise. After approximately 5 min the alkyl halide (1.2 equiv.) was carefully added portion-wise. The reaction mixture was stirred at 0 C or at RT for 15 min. to an hour then heated at 80 C for a period ranging between 30 min to 6 h. The reaction mixture was cooled to 0 C and quenched with water and treated with EtOAc and the organic layer separated. The organic solvent was dried (using either MgSO4, Na2SO4 or a phase separator) and subsequently removed under vacuum. The residue was purified by flash silica column chromatography or reverse phase column chromatography to give the product.General procedure: To a stirred solution of 6-bromo-1 H-pyrrolo[3, 2-c]pyridine (1 g, 5.07 mmol) in DMF (25 mL), CS2CO3 (4.95 g, 15.21 mmol) and 4-(bromomethyl)pyridine hydrobromide (1 .92 g, 7.60 mmol) were added. The resulting suspension was allowed to stir at rt, and then heated to 50C for 16 h. The reaction mixture was poured into ice water and extracted with EtOAc (2 x 120 mL). The organic layer was washed with water and brine solution, dried over anhydrous Na2S04, and filtered. The resulting solution was concentrated under reduced pressure to get a crude residue that was purified by flash column chromatography in 230-400 silica gel 70 % EtOAc/ pet ether as an eluent to afford the title compound (800 mg, 57.7 %) of the title compound as a light brown solid.General procedure: To a stirred solution of 6-bromo-1 H-pyrrolo[3, 2-c]pyridine (1 g, 5.07 mmol) in DMF (25 mL), CS2CO3 (4.95 g, 15.21 mmol) and 4-(bromomethyl)pyridine hydrobromide (1 .92 g, 7.60 mmol) were added. The resulting suspension was allowed to stir at rt, and then heated to 50C for 16 h. The reaction mixture was poured into ice water and extracted with EtOAc (2 x 120 mL). The organic layer was washed with water and brine solution, dried over anhydrous Na2S04, and filtered. The resulting solution was concentrated under reduced pressure to get a crude residue that was purified by flash column chromatography in 230-400 silica gel 70 % EtOAc/ pet ether as an eluent to afford the title compound (800 mg, 57.7 %) of the title compound as a light brown solid.General procedure: To a stirred solution of 6-bromo-1 H-pyrrolo[3, 2-c]pyridine (1 g, 5.07 mmol) in DMF (25 mL), CS2CO3 (4.95 g, 15.21 mmol) and 4-(bromomethyl)pyridine hydrobromide (1 .92 g, 7.60 mmol) were added. The resulting suspension was allowed to stir at rt, and then heated to 50C for 16 h. The reaction mixture was poured into ice water and extracted with EtOAc (2 x 120 mL). The organic layer was washed with water and brine solution, dried over anhydrous Na2S04, and filtered. The resulting solution was concentrated under reduced pressure to get a crude residue that was purified by flash column chromatography in 230-400 silica gel 70 % EtOAc/ pet ether as an eluent to afford the title compound (800 mg, 57.7 %) of the title compound as a light brown solid.To a stirred solution of tert-butyl 4-(methylsulfonyloxy)piperidine-1-carboxylate in DMF (30 mL), CS2CO3 (3.08 g. 9.5 mmol) and To a stirred solution of 6-bromo-1 H-pyrrolo[3, 2-c]pyridine (1 g, 5.07 mmol) in DMF (25 mL), CS2CO3 (4.95 g, 15.21 mmol) and 4-(bromomethyl)pyridine hydrobromide (1 .92 g, 7.60 mmol) were added. The resulting suspension was allowed to stir at rt, and then heated to 50C for 16 h. The reaction mixture was poured into ice water and extracted with EtOAc (2 x 120 mL). The organic layer was washed with water and brine solution, dried over anhydrous Na2S04, and filtered. The resulting solution was concentrated under reduced pressure to get a crude residue that was purified by flash column chromatography in 230-400 silica gel 70 % EtOAc/ pet ether as an eluent to afford the title compound (800 mg, 57.7 %) of the title compound as a light brown solid. LC-MS (method 15): Rt = 2.33 min; m/z = 288.27 (M+H*).To a stirred 40% NaOH aqueous solution (15 mL), 6-bromo-1 H-pyrrolo[3, 2-c]pyridine (1 g, 5.07 mmol), TBAB (163 mg, 0.50 mmol) and 1 , 2-dibromoethane (15 mL) were added. The resulting mixture was stirred at 80C for 12 h. The reaction mixture was quenched with water and extracted EtOAc. The organic layer was dried over anhydrous Na2S04, concentrated under reduced pressure to get a crude compound that was used for the next step without any further purification (1.8 g).LC-MS (method 6): R, = 1.77 min; m/z = 304.80 (M+H+)To a stirred solution of 6-bromo-1W-pyrrolo[3, 2-c]pyridine (1 g, 3.36 mmol) in DMF (20 mL), tetrahydro-2H- pyran-4-yl methanesulfonate (1.51 g, 8.38 mmol), and CS2CO3 (5.46g, 16.8 mmol) were added at 0C. The resulting mixture was stirrd at 100C for 16 h. The reaction mixture was diluted with EtOAc and washed with water. The the organic layer was dried over anhydrous a2S04, filtered and concentrate under reduced pressure. The crude residue was purified by column chromatography and eluted at 10%MeOH in DCM to afford the title compound (0.33 g, 35 %) as an off white solid. LC-MS (method 6): Rt = 1 .73 min; m/z = 281.07 (M+H+).

Molecular Weight:197.03
XLogP3:2
Hydrogen Bond Donor Count:1
Hydrogen Bond Acceptor Count:1
Exact Mass:195.96361
Monoisotopic Mass:195.96361
Topological Polar Surface Area:28.7
Heavy Atom Count:10
Complexity:129
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes