7-Bromo-5-fluoro-1,4-benzodiazine

4.00 g (19.509 mmol) of the compound from example 89A was dissolved in 100 ml ethanol and 2.42 g (19.509 mmol) of 2, 3-dihydroxy-l, 4-dioxane was added. The mixture was stirred for 4 h at room temperature and a further 2.42 g (19.509 mmol) of 2, 3-dihydroxy-l, 4-dioxane was added. After stirring for 24 h at room temperature, the mixture was concentrated in a rotary evaporator and the residue was purified by silica-gel chromatography (eluent: dichloromethane/methanol = 30:1). We obtained 3.60 g (80percent of theor.) of the target compound.LC-MS (method 1): R, = 1.79 min; MS (EIpos): m/z = 227 [M+H]EXAMPLE 365-Fluoro-7-[3-(piperidin-l-ylmethyl)phenyllquinoxalineGlyoxal (10 drops of a 40% solution in water) was added to a solution of 5- bromo-2, 3-diaminofluorobenzene (82 mg, 0.4 mmol) in ethanol (3 mL). The mixture was stirred and left to stand at r.t. for 1 h. The mixture was partitioned between water and EtOAc (20 mL each), and the organic phase was dried (MgSO4) and concentrated in vacuo. The residue was dissolved in DME (1.2 mL), and 3-(piperidin-l-ylmethyl)phenyl- boronic acid pinacol ester hydrochloride (135 mg, 0.4 mmol), 2M aqueous sodium carbonate solution (0.6 mL, 0.9 mmol) and Pd(PPh3)4 (14 mg, 0.012 mmol) were added. The mixture was heated to 12O0C in a sealed tube, under microwave irradiation, for 20 minutes. The mixture was partitioned between water and EtOAc (2 mL each), and the organic phase was concentrated in vacuo. The residue was purified by preparative HPLC to give the title compound (23 mg, 18% over the two steps) as a pale yellow-brown gum. deltaH (CDCl3) 8.94 (d, IH), 8.89 (d, IH), 8.17 (s, IH), 7.80 (d, IH), 7.72 (s, IH), 7.64 (d, IH), 7.48 (t, IH), 7.43 (d, IH), 3.64 (s, 2H), 2.40-2.60 (m, 4H), 1.55-1.70 (m, 4H), 1.39- 1.54 (m, 2H). LCMS (ES+) 322 (M+H)+, RT 2.25 minutes.EXAMPLE 365-Fluoro-7-[3-(piperidin-l-ylmethyl)phenyllquinoxalineGlyoxal (10 drops of a 40percent solution in water) was added to a solution of 5- bromo-2, 3-diaminofluorobenzene (82 mg, 0.4 mmol) in ethanol (3 mL). The mixture was stirred and left to stand at r.t. for 1 h. The mixture was partitioned between water and EtOAc (20 mL each), and the organic phase was dried (MgSO4) and concentrated in vacuo. The residue was dissolved in DME (1.2 mL), and 3-(piperidin-l-ylmethyl)phenyl- boronic acid pinacol ester hydrochloride (135 mg, 0.4 mmol), 2M aqueous sodium carbonate solution (0.6 mL, 0.9 mmol) and Pd(PPh3)4 (14 mg, 0.012 mmol) were added. The mixture was heated to 12O0C in a sealed tube, under microwave irradiation, for 20 minutes. The mixture was partitioned between water and EtOAc (2 mL each), and the organic phase was concentrated in vacuo. The residue was purified by preparative HPLC to give the title compound (23 mg, 18percent over the two steps) as a pale yellow-brown gum. deltaH (CDCl3) 8.94 (d, IH), 8.89 (d, IH), 8.17 (s, IH), 7.80 (d, IH), 7.72 (s, IH), 7.64 (d, IH), 7.48 (t, IH), 7.43 (d, IH), 3.64 (s, 2H), 2.40-2.60 (m, 4H), 1.55-1.70 (m, 4H), 1.39- 1.54 (m, 2H). LCMS (ES+) 322 (M+H)+, RT 2.25 minutes.Under an argon atmosphere, 750 mg (0.819 mmol) of tris-(dibenzylidene-acetone)-dipalladium(0) and 551 mg (1.966 mmol) of tricyclohexylphosphine were dissolved in 80 ml dioxane. |814 mg - -(15.019 mmol) of 4, 4, 414'5, 5, 5'5'-octamethyl-2, 2t-bi-l, 3, 2-dioxaborolan, 3100 mg (13.654 mmol) of the compound from example 9OA and 2010 mg (20.4813 mmol) potassium acetate were added and the mixture was stirred overnight at 800C. After cooling, dioxane was added to the reaction mixture and it was filtered on Celite. The filtrate was concentrated in a rotary evaporator at reduced pressure and dried under high vacuum. We obtained 7.08 g of the raw product (purity 69% according to GC-MS), which was reacted further without further purification.GC-MS (method 6): R, = 6.78 min; MS (EIpos): m/z = 274 [M]+.4.00 g (19.509 mmol) of the compound from example 89A was dissolved in 100 ml ethanol and 2.42 g (19.509 mmol) of 2, 3-dihydroxy-l, 4-dioxane was added. The mixture was stirred for 4 h at room temperature and a further 2.42 g (19.509 mmol) of 2, 3-dihydroxy-l, 4-dioxane was added. After stirring for 24 h at room temperature, the mixture was concentrated in a rotary evaporator and the residue was purified by silica-gel chromatography (eluent: dichloromethane/methanol = 30:1). We obtained 3.60 g (80percent of theor.) of the target compound.LC-MS (method 1): R, = 1.79 min; MS (EIpos): m/z = 227 [M+H]+.1H-NMR (400 MHz, DMSO-D5): delta [ppm] = 8.06 (dd, IH), 8.24 (t, IH), 9.05 (d, IH), 9.07 (d, IH).

Molecular Weight:227.03
XLogP3:2
Hydrogen Bond Acceptor Count:3
Exact Mass:225.95419
Monoisotopic Mass:225.95419
Topological Polar Surface Area:25.8
Heavy Atom Count:12
Complexity:167
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes