4-phenoxybutan-1-amine

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

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

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

Procedure: In a three-necked flask of 25 ml provided with a magnetic bar, a calcium chloride tube and a dropping funnel, 1.99 gr (0.012 mol) of phenoxybutylamine, 1 gr (0.012 mol) of n-butylisonitrile and 0.72 gr of acetic acid were mixed in 5 ml of methanol. A precipitate of phenoxybutylamine acetate formed. This suspension cooled in an ice bath was added under good agitation with 0.87 gr (0.012 mol) of isobutyraldehyde. In a three-necked flask of 25 ml provided with a magnetic bar, a calcium chloride tube and a dropping funnel

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

Procedure: In a three-necked flask of 25 ml provided with a magnetic bar, a calcium chloride tube and a dropping funnel, 1.99 gr (0.012 mol) of phenoxybutylamine, 1 gr (0.012 mol) of n-butylisonitrile and 0.72 gr of acetic acid were mixed in 5 ml of methanol. A precipitate of phenoxybutylamine acetate formed. This suspension cooled in an ice bath was added under good agitation with 0.87 gr (0.012 mol) of isobutyraldehyde. In a three-necked flask of 25 ml provided with a magnetic bar, a calcium chloride tube and a dropping funnel

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

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

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

Procedure: The title compound was prepared as described for Example 24 from 1 equivalent of (4-phenoxybutyl)amine, 2-tert-butyl-4-chloro-5-phenylisothiazol-3(2H)-one 1,1-dioxide and 1 equivalent TEA at 100° C. The residue was purified by silica gel column chromatography (Horizons Biotage) using 10-20% EtOAc in hexane as eluent giving the title compound (0.172 g, 80%) as a solid. 1H NMR (500 MHz CDCl3): 1H NMR (500 MHz CDCl3): δ 7.54-7.50 (m, 2H), 7.44-7.38 (m, 3H), 7.32-7.25 (m, 2H), 6.96 (t, 1H), 6.83 (d, 2H), 5.34 (t, 1H), 3.81 (t, 2H), 2.98-2.90 (m, 2H), 1.75 (s, 9H), 1.64-1.53 (m, 4H); 13C NMR (125 MHz CDCl3): δ 159.9, 158.9, 135.2, 131.8, 129.8, 129.7, 128.8, 125.3, 121.0, 114.6, 107.2, 67.1, 61.7, 43.9, 27.9, 26.6, 26.4; Mass Spectrum: M+H+ 429. The title compound was prepared The residue was purified by silica gel column chromatography (Horizons Biotage)

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

Procedure: A mixture of 2-(4-phenoxybutyl)1H-isoindole-1,3(2H)-dione (10.10 g, 3.27 mmol) and 25% hydrazine solution in water (2.88 ml, 13.10 mmol) in EtOH (30 ml) was warmed at reflux. After 1.5 h, EtOAc was added and the mixture was extracted with brine. The combined aqueous phases were then re-extracted with EtOAc and all the organic phases combined. These were then extracted with 1N HCl, the acidic aqueous phases combined, basified with 2N NaOH and re-extracted into EtOAc before evaporating to dryness to give the title compound (0.411 mg, 67%) as an oil. 1H NMR (500 MHz CDCl3): δ 7.32-2.26 (m, 2H), 6.95 (t, 1H), 4.00 (t, 2H), 2.80 (t, 2H), 1.90-1.82 (m, 2H), 1.68-1.62 (m, 2H). was warmed at reflux the mixture was extracted with brine The combined aqueous phases were then re-extracted with EtOAc and all the organic phases These were then extracted with 1N HCl re-extracted into EtOAc before evaporating to dryness

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

Procedure: A mixture of 2-(4-phenoxybutyl)1H-isoindole-1,3(2H)-dione (10.10 g, 3.27 mmol) and 25% hydrazine solution in water (2.88 ml, 13.10 mmol) in EtOH (30 ml) was warmed at reflux. After 1.5 h, EtOAc was added and the mixture was extracted with brine. The combined aqueous phases were then re-extracted with EtOAc and all the organic phases combined. These were then extracted with 1N HCl, the acidic aqueous phases combined, basified with 2N NaOH and re-extracted into EtOAc before evaporating to dryness to give the title compound (0.411 mg, 67%) as an oil. 1H NMR (500 MHz CDCl3): δ 7.32-2.26 (m, 2H), 6.95 (t, 1H), 4.00 (t, 2H), 2.80 (t, 2H), 1.90-1.82 (m, 2H), 1.68-1.62 (m, 2H). was warmed at reflux the mixture was extracted with brine The combined aqueous phases were then re-extracted with EtOAc and all the organic phases These were then extracted with 1N HCl re-extracted into EtOAc before evaporating to dryness

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

Procedure: The title compound was prepared as described for Example 24 from 1 equivalent of (4-phenoxybutyl)amine, 2-tert-butyl-4-chloro-5-phenylisothiazol-3(2H)-one 1,1-dioxide and 1 equivalent TEA at 100° C. The residue was purified by silica gel column chromatography (Horizons Biotage) using 10-20% EtOAc in hexane as eluent giving the title compound (0.172 g, 80%) as a solid. 1H NMR (500 MHz CDCl3): 1H NMR (500 MHz CDCl3): δ 7.54-7.50 (m, 2H), 7.44-7.38 (m, 3H), 7.32-7.25 (m, 2H), 6.96 (t, 1H), 6.83 (d, 2H), 5.34 (t, 1H), 3.81 (t, 2H), 2.98-2.90 (m, 2H), 1.75 (s, 9H), 1.64-1.53 (m, 4H); 13C NMR (125 MHz CDCl3): δ 159.9, 158.9, 135.2, 131.8, 129.8, 129.7, 128.8, 125.3, 121.0, 114.6, 107.2, 67.1, 61.7, 43.9, 27.9, 26.6, 26.4; Mass Spectrum: M+H+ 429. The title compound was prepared The residue was purified by silica gel column chromatography (Horizons Biotage)

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

Procedure: A mixture of 2-(4-phenoxybutyl)1H-isoindole-1,3(2H)-dione (10.10 g, 3.27 mmol) and 25% hydrazine solution in water (2.88 ml, 13.10 mmol) in EtOH (30 ml) was warmed at reflux. After 1.5 h, EtOAc was added and the mixture was extracted with brine. The combined aqueous phases were then re-extracted with EtOAc and all the organic phases combined. These were then extracted with 1N HCl, the acidic aqueous phases combined, basified with 2N NaOH and re-extracted into EtOAc before evaporating to dryness to give the title compound (0.411 mg, 67%) as an oil. 1H NMR (500 MHz CDCl3): δ 7.32-2.26 (m, 2H), 6.95 (t, 1H), 4.00 (t, 2H), 2.80 (t, 2H), 1.90-1.82 (m, 2H), 1.68-1.62 (m, 2H). was warmed at reflux the mixture was extracted with brine The combined aqueous phases were then re-extracted with EtOAc and all the organic phases These were then extracted with 1N HCl re-extracted into EtOAc before evaporating to dryness

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

Procedure: 4-(4,6-Dimethoxy-1,3,5-triazin-2-yl)-4-methylmorpholin-4-ium chloride (DMT-MM) (69 mg, 0.25 mmol) was added to a solution of N-(2-{[3-chloro-4-(2-methylbenzoyl)phenyl]amino}phenyl)-succinamic acid (100 mg, 0.23 mmol) (disclosed in WO 01/05746) and 4-phenoxybutylamine (30 mg, 0.25 mmol) in methanol (2.0 mL). The reaction mixture was stirred at room temperature for 18 h. The reaction mixture was poured into 1 N HCl (aq.) and was extracted with EtOAc (×2). The combined organic phases were washed with water, dried (MgSO4), filtered and concentrated in vacuo. The crude product was purified by flash chromatography using DCM/MeOH/NH3(aq.) 95:5:0.5 as the eluent to afford the title compound as a yellow solid. was extracted with EtOAc (×2) The combined organic phases were washed with water dried (MgSO4) filtered concentrated in vacuo The crude product was purified by flash chromatography