6-Chloro-2-naphthoic acid

Synthesis of Compound 68 6-chloro-2-naphthoic acid686-chloro-2 -naphthoic acidA suspension of 6-bromo-2-naphthoic acid (3.0 g, 11.47 mmol), CuCI (1 1.7 g, 114.64 mmol) and CuI (2.19 g, 1 1.50 mmol) in degassed DMF (45 ml.) was heated to reflux under argon in dark for 4 hrs. After cooling to room temperature, the solution was decanted into HA suspension of 6-bromo-2-naphthoic acid (3.0 g, 11.47 mmol), CuCI (1 1.7 g, 114.64 mmol) and CuI (2.19 g, 1 1.50 mmol) in degassed DMF (45 ml.) was heated to reflux under argon in dark for 4 hrs. After cooling to room temperature, the solution was decanted into HA suspension of 6-bromo-2-naphthoic acid (3.0 g, 11.47 mmol), CuCl (11.7 g, 114.64 mmol) and CuI (2.19 g, 11.50 mmol) in degassed DMF (45 mL) was heated to reflux under argon in dark for 4 hrs.Step 1. Example 32 Example 66 - Synthesis of Compound 68 6-chloro-2-naphthoic acid686-chloro-2 -naphthoic acidA suspension of 6-bromo-2-naphthoic acid (3.0 g, 11.47 mmol), CuCI (1 1.7 g, 114.64 mmol) and CuI (2.19 g, 1 1.50 mmol) in degassed DMF (45 ml.) was heated to reflux under argon in dark for 4 hrs. After cooling to room temperature, the solution was decanted into HA suspension of 6-bromo-2-naphthoic acid (3.0 g, 11.47 mmol), CuCI (1 1.7 g, 114.64 mmol) and CuI (2.19 g, 1 1.50 mmol) in degassed DMF (45 ml.) was heated to reflux under argon in dark for 4 hrs. After cooling to room temperature, the solution was decanted into HA suspension of 6-bromo-2-naphthoic acid (3.0 g, 11.47 mmol), CuCl (11.7 g, 114.64 mmol) and CuI (2.19 g, 11.50 mmol) in degassed DMF (45 mL) was heated to reflux under argon in dark for 4 hrs.Step 1. Example 32 Synthesis of Compound 32 6-chloro-2-naphthoic acid A suspension of 6-bromo-2-naphthoic acid (3.0 g, 11.47 mmol), CuCl (11.7 g, 114.64 mmol) and CuI (2.19 g, 11.50 mmol) in degassed DMF (45 mL) was heated to reflux under argon in dark for 4 hrs. After cooling to room temperature, the solution was decanted into H2O (200 mL) and the resulting mixture was extracted with EtOAc (2*500 mL). The combined organic layers were then washed with H2O (4*500 mL) followed by brine (1*500 mL), dried over MgSO4, filtered and concentrated under reduced pressure to dryness. The residue was trituated with CH3CN and the solid obtained was then re-crystallized from EtOAc to give the pure product 32 (2.2 g, 93%) as an off-white solid. HPLC tR 6.47 min.Example 66 - Synthesis of Compound 68 6-chloro-2-naphthoic acid686-chloro-2 -naphthoic acidA suspension of 6-bromo-2-naphthoic acid (3.0 g, 11.47 mmol), CuCI (1 1.7 g, 114.64 mmol) and CuI (2.19 g, 1 1.50 mmol) in degassed DMF (45 ml.) was heated to reflux under argon in dark for 4 hrs. After cooling to room temperature, the solution was decanted into H2O (200 ml.) and the resulting mixture was extracted with EtOAc (2 x 500 mL). The combined organic layers were then washed with H2O (4 x 500 mL) followed by brine (1 x 500 mL), dried over MgSO4, filtered and concentrated under reduced pressure to dryness. The residue was trituated with CH3CN and the solid obtained was then re-crystallized from EtOAc to give the pure product 68 (2.2 g, 93%) as a off-white solid. HPLC fR 6.47 min.A suspension of 6-bromo-2-naphthoic acid (3.0 g, 11.47 mmol), CuCI (1 1.7 g, 114.64 mmol) and CuI (2.19 g, 1 1.50 mmol) in degassed DMF (45 ml.) was heated to reflux under argon in dark for 4 hrs. After cooling to room temperature, the solution was decanted into H2O (200 ml.) and the resulting mixture was extracted with EtOAc (2 x 500 ml_). The combined organic layers were then washed with H2O (4 x 500 ml.) followed by brine (1 x 500 ml_), dried over MgSO4, filtered and concentrated under reduced pressure to dryness. The residue was trituated with CH3CN and the solid obtained was then re-crystallized from EtOAc to give the pure product 70 (2.2 g, 93%) as a off-white solid. HPLC fe 6.47 minA suspension of 6-bromo-2-naphthoic acid (3.0 g, 11.47 mmol), CuCl (11.7 g, 114.64 mmol) and CuI (2.19 g, 11.50 mmol) in degassed DMF (45 mL) was heated to reflux under argon in dark for 4 hrs. After cooling to room temperature, the solution was decanted into H2O (200 mL) and the resulting mixture was extracted with EtOAc (2*500 mL). The combined organic layers were then washed with H2O (4*500 mL) followed by brine (1*500 mL), dried over MgSO4, filtered and concentrated under reduced pressure to dryness. The residue was trituated with CH3CN and the solid obtained was then re-crystallized from EtOAc to give the pure product 68 (2.2 g, 93%) as a off-white solid. HPLC tR 6.47 min.Step 1. To a solution of 6-bromo-2-naphthoic acid (4.4 g, 17.5 mmol) in 50 mL anhydrous DMF were added CuCl (8.7 g, 87.5 mmol) and CuI (0.2 g). The slurry was refluxed for 1 hour. At room temperature it was diluted with 300 mL EtOAc and stirred for 2 hours. It was filtered through celite. The filtrate was evaporated in vacuuo to afford 6-chloro-2-naphthoic acid (2.7 g, 75%). ES-MS: (M+H)+207.6-Bromo-2-naphthoic acid (9.00 g, 35.85 mmol) and DMF (140 mL) were combined, stirred, and degassed with subsurface N2 for 10 minutes before adding CuCl (35.49 g, 358.50 mmol) and Cul (6.96 g, 36.57 mmol). The reaction vessel was wrapped in aluminum foil and refluxed for 5 h under a nitrogen atmosphere. The mixture was allowed to cool to 60 C then filtered through celite. The filtrate was diluted with EtOAc and 1 M HCl. The organic phases were washed once more with 1 M HCl, water (2X) and concentrated in vacuo. The resulting crude solid was suspended in acetonitrile, stirred for 1 hr, and filtered to afford 6-chloro-2-naphthoic acid as a white solid.A mixture of 6-bromo-2-naphthoic acid (Compound 106A) (3.00 g, 11.47 mmol), Cul (2.19 g, 11.50 mmol), and CuCl (11.70 g, 114.64 mmol) in DMF (20 mL) was stirred at 150 C under nitrogen for 3 hours. The mixture was cooled down to room temperature and diluted with an aqueous HC1 solution (3 M, 100 mL). A solid was formed, filtered, and washed with water (100 mL). It was suspended in THF (100 mL), filtered, and washed with THF (100 mL). The combined filtrates were concentrated under reduced pressure. The residue was suspended in an aqueous HC1 solution (3 M, 100 mL), stirred at room temperature for 10 minutes, and filtered. The cake was washed with water (50 mL) and CH3CN (50 mL) and dried under vacuum to yield Compound 106B. LC-MS (ESI) m/z: 205 [M-H] ; 1H-NMR (DMSO-r/r, , 400 MHz): d (ppm) 7.61-7.64 (m, 1H), 7.99-8.05 (m, 2H), 8.15-8.19 (m, 2H), 8.65 (s, 1H), 13.18 (s, 1H).A mixture of Compound 106B (3.00 g, 14.56 mmol), N, O- dimethylhydroxylamine hydrochloride (1.71 g, 17.47 mmol), Et3N (4.41 g, 43.68 mmol), and HATU (8.30 g, 21.84 mmol) in dichloromethane (30 mL) was stirred at room temperature for 4 hours. The mixture was diluted with ethyl acetate (160 mL), washed with water (100 mL) and brine (100 mL), and concentrated. The residue was purified with flash column chromatography on silica gel (ethyl acetate in petroleum ether from 0% to 80% v/v) to yield Compound 106C. LC-MS (ESI) m/z: 250 [M+H]+; 1H-NMR (DMSO-4, 400 MHz): d (ppm) 3.31 (s, 3H), 3.56 (s, 3H), 7.59-7.62 (m, 1H), 7.71-7.74 (m, 1H), 7.97 (d, J= 8.8 Hz, 1H), 8.08-8.12 (m, 2H), 8.24 (s, 1H).

Molecular Weight:206.62
XLogP3:3.9
Hydrogen Bond Donor Count:1
Hydrogen Bond Acceptor Count:2
Rotatable Bond Count:1
Exact Mass:206.0134572
Monoisotopic Mass:206.0134572
Topological Polar Surface Area:37.3
Heavy Atom Count:14
Complexity:229
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes