Reaction SMILES: [N+:1]([C:4]1[CH:5]=[C:6]([C:14]([OH:16])=[O:15])[C:7]2[C:12]([CH:13]=1)=[CH:11][CH:10]=[CH:9][CH:8]=2)([O-:3])=[O:2].[C:17](Cl)(=O)C(Cl)=O.CN(C)C=O.CO>ClCCl>[N+:1]([C:4]1[CH:5]=[C:6]([C:14]([O:16][CH3:17])=[O:15])[C:7]2[C:12]([CH:13]=1)=[CH:11][CH:10]=[CH:9][CH:8]=2)([O-:3])=[O:2]
Reactant: O=C(Cl)C(=O)Cl
Reactant: O=C(O)c1cc([N+](=O)[O-])cc2ccccc12
Solvent: ClCCl
Solvent: CO
Solvent: CN(C)C=O
Product: COC(=O)c1cc([N+](=O)[O-])cc2ccccc12
Temperature: 25 °C
Reaction time: 1 h

Procedure:
To a suspension of 22.0 g (0.101 mol) of 3-nitro-1-napthalene-carboxylic acid (prepared according to procedures in Duffy, K. J., et al., in J. Med. Chem. 2001, 44, 3730-3745) in 1 L of anhydrous dichloromethane at 0° C. under an atmosphere of nitrogen was added 9.8 mL (0.11 mol) of oxalyl chloride followed by 0.80 mL (10 mmol) of anhydrous N,N-dimethylformamide. The reaction mixture was allowed to gradually warm to ambient temperature for 3 h until gas evolution ceased. The resulting homogeneous solution was concentrated in vacuo to remove all volatiles. The residue was then dissolved in 1 L of anhydrous dichloromethane and 20 mL (0.51 mol) of anhydrous methanol was added. After stirring for 1 h, the reaction was carefully quenched with a saturated aqueous sodium bicarbonate solution (500 mL). The organic layer was separated and the aqueous layer was extracted with dichloromethane (2×250 mL). The combined organic layers were washed with brine (300 mL), dried over magnesium sulfate, filtered and concentrated in vacuo to yield the title compound as a pale yellow solid, which was used without further purification. LC/MS 232.2 (M+1). Step B: Methyl 3-amino-1-naphthoate. To 1.15 g (1.08 mmol) of 10% palladium on carbon was added a suspension of 11.6 g (50.0 mmol) of the above methyl 3-nitro-1-naphthoate in 150 mL of anhydrous ethanol and 40 mL of anhydrous dichloromethane. The resulting suspension was agitated under an atmosphere of hydrogen at 40 psi for 3 h during which time all solids dissolved. The reaction mixture was filtered through a plug of Celite®, which was subsequently washed with dichloromethane (300 mL). The combined filtrates were concentrated in vacuo to yield the title compound as a pale green gum which was used without further purification. LC/MS 202.1 (M+1). Step C: Methyl 3-bromo-1-naphthoate. A solution of 4.34 g (62.9 mmol) of sodium nitrite in 40 mL of water was added dropwise to a 0° C. solution of 11.5 g (57.2 mmol) of the above methyl 3-amino-1-naphthoate in 300 mL of ethanol and 60 mL of 48% aqueous hydrobromic acid while maintaining an internal reaction temperature below 10° C. After complete addition of the aqueous solution the resulting dark red reaction mixture was stirred at 0° C. for an additional 30 min. The cooled (0° C.) reaction mixture was then added over 20 min. to a suspension of 8.21 g (57.2 mmol) of cuprous bromide in 60 mL of ethanol and 60 mL of 48% aqueous hydrobromic acid heated to 95° C. After stirring for 30 min. the reaction mixture was cooled to 0° C. and carefully partitioned between ethyl ether (250 mL) and water (600 mL). The organic layer was separated and the aqueous layer was extracted with ethyl ether (2×300 mL). The combined organic layers were washed with brine (100 mL), dried over magnesium sulfate, filtered and concentrated in vacuo. The residue was passed through a plug of silica gel eluting with 30% dichloromethane in hexanes and the filtrate concentrated in vacuo. Flash chromatography on a Biotage® purification apparatus (silica gel, 7% dichloromethane/hexanes) yielded the title compound as a colorless solid. 1H NMR (DMSO-d6): δ 8.67 (d, J=8.4 Hz, 1H), 8.50 (s, 1H), 8.15 (s, 1H), 8.02 (d, J=8.0 Hz, 1H), 7.68-7.71 (m, 1H), 7.63-7.66 (t, J=7.6 Hz, 1H), 3.94 (s, 3H). LC/MS 265.0 (M+1) and 267.0 (M+3). Step D: tert-Butyl 4-[4-(methoxycarbonyl-2-naphthyl]-1-piperazinecarboxylate. To 670 mg (2.53 mmol) of the compound from Step C and 517 mg (2.78 mmol) of tert-butyl 1-piperazinecarboxylate in a dry 50 mL flask was added 20 mL anhydrous dioxane. The system was purged for 5 min., and then flushed with nitrogen. 1.23 g (3.80 mmol) of cesium carbonate was added to the flask, and the system was again purged for 5 min with nitrogen, then flushed with nitrogen. Next, 60 mg (0.1 5 mmol) of 2-dicyclohexylphosphino-2′(N,N-dimethylamino)biphenyl, and 73 mg (0.13 mmol) of bis(dibenzylideneacetone)palladium were added, and the system was purged with nitrogen one last time. The reaction mixture was heated at 85° C. under nitrogen for 24 h. After cooling to room temperature, the solution was filtered through Celite® and concentrated in vacuo to yield an orange oil, which was purified using a Biotage Horizon® system (10%-25% ethyl acetate in hexanes gradient) to give the title compound. LC/MS: 371.2 (M+1) Step E: Methyl 3-(1-piperazinyl)-1-naphthoate trifluoroacetic acid salt. To 120 mg (0.324 mmol) of the compound from Step D was added 5 mL dichloromethane and 0.5 mL trifluoroacetic acid. When the reaction was complete by LC-MS (1 h), the solution was concentrated in vacuo. The resulting oil was triturated with ethyl ether (3 mL) and filtered to give the title compound as a pale green solid. 1H NMR (CD3OD): δ 8.64 (d, J=8.2 Hz, 1H), 7.99 (d, J=2.5 Hz, 1H), 7.81 (d, J=8.0 Hz, 1H), 7.46 (m, 3H), 3.98 (s, 3H), 3.54 (t, J=4.8 Hz, 4H), 3.43 (t, J=5.5 Hz, 4H). LC/MS 271.0 (M+1).