(3-fluoro-4-methoxyphenyl)methanamine

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of 3-fluoro-4-(methyloxy)benzamide (100 mg, 0.60 mmol) in tetrahydrofuran (5 mL) was added sodium borohydride (115 mg, 3.0 mmol) followed by the drop-wise addition of a solution of borontrifluoride etherate (48% BF3 ca., 475 μl, 3.8 mmol) in tetrahydrofuran (3 mL). The mixture was stirred at reflux for 15 hours, then was cooled to room temperature and diluted with ethyl acetate. The organic portion was extracted with 20% aqueous citric acid. The aqueous portion was brought to pH 8 using solid sodium bicarbonate, then was extracted several times using ethyl acetate. The combined organic portion was washed with brine then dried over anhydrous sodium sulfate. Filtration and concentration afforded a yellow residue, which was purified by silica gel column chromatography using 10% methanol in dichloromethane as eluent. Purified fractions were pooled and concentrated to afford 56 mg, 0.36 mmol (61%) of 3-fluoro-4-methoxybenzylamine as a colorless residue. MS (EI) for C8H10FNO: 156 (MH+). at reflux for 15 hours The organic portion was extracted with 20% aqueous citric acid was extracted several times The combined organic portion was washed with brine then dried over anhydrous sodium sulfate Filtration and concentration afforded a yellow residue, which was purified by silica gel column chromatography concentrated

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: In DCM (50 mL) were dissolved ethyl 4-chloro-2-(methylthio)pyrimidine-5-carboxylate (1.5 g, 6.46 mmol), 3-fluoro-4-methoxybenzylamine (1.0 g, 6.45 mmol) and triethylamine (1.3 g, 12.9 mmol). The reaction mixture was stirred at ambient temperature for 30 min, and washed with water. The organic phase was dried over sodium sulfate and concentrated to give ethyl 4-((3-fluoro-4-methoxybenzyl)amino)-2-(methylthio)pyrimidine-5-carboxylate as a yellow oil (2.2 g, yield: 97%). washed with water The organic phase was dried over sodium sulfate concentrated

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: The title compound was prepared following the same general protocol as described in Steps 8-9, Example 1, using 3-fluoro-4-methoxybenzylamine and 1-((2′-(tert-butoxycarbonyl)biphenyl-4-yl)methyl)-2,3-dimethyl-1H-indole-5-carboxylic acid. LC-MS 537 (M+H).

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of 3-fluoro-4-(methyloxy)benzamide (100 mg, 0.60 mmol) in tetrahydrofuran (5 mL) was added sodium borohydride (115 mg, 3.0 mmol) followed by the drop-wise addition of a solution of borontrifluoride etherate (48% BF3 ca., 475 μl, 3.8 mmol) in tetrahydrofuran (3 mL). The mixture was stirred at reflux for 15 hours, then was cooled to room temperature and diluted with ethyl acetate. The organic portion was extracted with 20% aqueous citric acid. The aqueous portion was brought to pH 8 using solid sodium bicarbonate, then was extracted several times using ethyl acetate. The combined organic portion was washed with brine then dried over anhydrous sodium sulfate. Filtration and concentration afforded a yellow residue, which was purified by silica gel column chromatography using 10% methanol in dichloromethane as eluent. Purified fractions were pooled and concentrated to afford 56 mg, 0.36 mmol (61%) of 3-fluoro-4-methoxybenzylamine as a colorless residue. MS (EI) for C8H10FNO: 156 (MH+). at reflux for 15 hours The organic portion was extracted with 20% aqueous citric acid was extracted several times The combined organic portion was washed with brine then dried over anhydrous sodium sulfate Filtration and concentration afforded a yellow residue, which was purified by silica gel column chromatography concentrated