Ammonium Chloride → HCID 21101416, compound

Temperature

80 °C

This acid (0.14 g, 0.5 mmol) was dissolved in dichloromethane (2 ml) and oxalyl chloride added (87 μl, 1 mmol). The mixture was stirred for 60 min at room temperature under argon. The solvent was evaporated and the residue added to a solution of 3-methoxy-4-(2-pyrrolidin-1-ylethoxy)phenylamine [Example A4] (0.10 g, 0.44 mmol) and triethylamine (70 μl, 0.5 mmol) in dichloromethane (4 ml). The mixture was stirred for 90 mins at room temperature under argon and then washed with a saturated aqueous solution of NaHCO3 (5 ml) and brine (5 ml). The organic layer was dried over MgSO4, the solvent evaporated and the residue purified by flash chromatography on silica gel (eluting with methanol-dichloromethane-aq. ammonia). 4′-Chloro-4-nitrobiphenyl-3-carboxylic acid [3-methoxy-4-(2-pyrrolidin-1-ylethoxy)phenyl]amide was obtained in 54% yield; m/z [APCI+] 496 (100%, M+H+). Iron powder (45 mg, 0.81 mmol) and ammonium chloride (72 mg, 1.35 mmol) were mixed in water (2 ml) and 4′-chloro-4-nitrobiphenyl-3-carboxylic acid [3-methoxy-4-(2-pyrrolidin-1-ylethoxy)phenyl]amide (0.13 g, 0.27 mmol) added, dissolved in MeOH (2 ml). The mixture was heated at 80° C. for 90 min and then filtered while hot. Dichloromethane (30 ml) was added to the cooled filtrate. The organic layer was washed with water (10 ml), saturated aqueous NaHCO3 (10 ml) and brine (10 ml), then dried and the solvent evaporated to give a yellow gum. This was dissolved in 1,2-dichloroethane (10 ml) and triethylorthoformate (4 ml). The mixture was refluxed for 16 h under argon, then after cooling DBU (0.2 ml) was added and the mixture was stirred for 10 mins at room temperature. The solvent was evaporated and the residue purified by flash chromatography on silica gel (eluting with methanol-dichloromethane-aqueous ammonia) to yield the title compound as an orange gum;

1. filtrationfiltered while hot
2. additionDichloromethane (30 ml) was added to the cooled filtrate
3. washThe organic layer was washed with water (10 ml), saturated aqueous NaHCO3 (10 ml) and brine (10 ml)
4. customdried
5. customthe solvent evaporated
6. customto give a yellow gum
7. temperatureThe mixture was refluxed for 16 h under argon
8. additionwas added
9. customThe solvent was evaporated
10. customthe residue purified by flash chromatography on silica gel (eluting with methanol-dichloromethane-aqueous ammonia)

ORD record

ord-60f185bbb5214257908ea1a5aaf74443

Source dataset

uspto-grants-2007_05

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07220777B2