N-ethylbutan-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:

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

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

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

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

Conditions: temp:177.51; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A mixture of 4-chloro-3,6-dimethyl-1-(2,4,6-trimethylphenyl)-1H-pyrazolo[3,4-b]pyridine (98 mg, 0.33 mmol), N-butylethylamine (1 ml) in DMSO (2 ml) was heated in an oil bath at 175-180° C. for 20 hours. The reaction mixture was quenched with saturated ammonium chloride and extracted with EtOAc. The organic layer was washed with brine, dried, and concentrated to give a brown oil. The oil residue was purified through silica gel column chromatography using EtOAc/Hexane in a ratio of 1/9 as eluent to give a colorless oil. 1H NMR (CDCl3) 6.92 (s, 2H), 6.29 (s, 1H), 3.42 (q, 2H), 3.27 (t, 2H), 2.65 (s, 3H), 2.44 (s, 3H), 2.30 (s, 3H), 1.91 (s, 6H), 1.57 (m, 2H), 1.33 (m, 2H), 1.13 (t, 3H), 0.90 (t, 3H) ppm. IR (neat) 2960, 2920, 1570 cm−1. High MS, calc. 364.2627, found 364.26306. The reaction mixture was quenched with saturated ammonium chloride extracted with EtOAc The organic layer was washed with brine dried concentrated to give a brown oil The oil residue was purified through silica gel column chromatography to give a colorless oil

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

Procedure: Part A. A solution of 4,6-dichloro-2-methyl-5-nitropyrimidine (prepared using the methods of Albert, et al., J. Chem. Soc. 1954, p. 3832) (2.77 g, 13.3 mmol) in absolute ethanol (25 mL) was cooled to 0° C., and treated with triethylamine (2.00 mL, 14.3 mmol). Then, a solution of ethylbutylamine (1.80 mL, 13.2 mmol) in ethanol (3 mL) was added dropwise with stirring. The mixture was allowed to stir and warm to ambient temperature overnight, then was partitioned between water and ethyl acetate (100 mL each). The organic phase was seperated, washed with satd. aq. brine (100 mL), dried over anhydrous sodium sulfate, filtered and evaporated. The residue was separated by column chromatography (silica gel, dichloromethane) to afford 4-chloro-6-(ethylbutylamino)-2-methyl-5-nitropyrimidine as an oil (3.34 g, 12.2 mmol, 92%). Spectral data: TLC RF 0.59 (dichloromethane). 1H NMR (300 MHz, CDCl3): δ3.45 (2H, q, J=7.0 Hz), 3.38 (2H, t, J=7.7 Hz), 2.50 (3H, s), 1.62-1.52 (2H, m), 1.38-1.26 (2H, m), 1.20 (3H, t, J=7.0 Hz), 0.94 (3H, t, J=7.3 Hz). MS (NH3—CI): m/e 276 (4), 275 (40), 274 (16), 273 (100). to stir was partitioned between water and ethyl acetate (100 mL each) The organic phase was seperated washed with satd aq. brine (100 mL), dried over anhydrous sodium sulfate filtered evaporated The residue was separated by column chromatography (silica gel, dichloromethane)

Conditions: temp:135.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A mixture of [(6-chloro-2-methylpyrimidin-4-yl)-(2,4,6-trimethylphenyl)-amino]-acetic acid ethyl ester (85 mg, 0.244 mmol) and N-butyl-ethylamine (0.17 ml, 1.1 mmol) in 4 ml DMSO was heated at 135° C. for 15 hours. An additional 1 ml of N-butyl-ethylamine was added and the reaction was heated at that temperature for an additional 15 hours (tlc showed no starting material). The mixture was quenched with water and extracted with ethyl acetate. The organic layer was separated, dried and concentrated to give 123 mg of a light amber oil. The oil was purified through silica gel chromatotron using 5% ethyl acetate in hexane as eluent to give 92 mg (91%) of the title compound as a white glass. 1H NMR (CDCl3) δ 6.94 (s, 2H), 4.69 (s, 1H), 4.23 (s, 2H), 4.22 (q, 2H), 3.35 (q, 2H), 3.15 (t, 2H), 2.36 (s, 3H), 2.31 (s, 3H), 2.21 (s, 6H), 1.3-1.5 (m, 2H), 1.34 (t, 3H), 1.1-1.3 (m, 2H), 1.01 (t, 3H), 0.80 (t, 3H) ppm. the reaction was heated at that temperature for an additional 15 hours (tlc The mixture was quenched with water extracted with ethyl acetate The organic layer was separated dried concentrated

Conditions: temp:160.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A mixture of (6-chloro-2,5-dimethyl-pyrimidin-4-yl)-methyl-(2,4,6-trimethylphenyl)-amine (200 mg) and N-butyl-ethylamine (0.3 ml) in 1 ml of DMSO was heated in oil bath of 160° C. for 15 hours. The mixture was quenched with water and extracted with ethyl acetate. The organic layer was separated, dried and concentrated to give the crude material. After silica gel column purification using chloroform as eluent, the title compound was obtained as an oil. 1H NMR (CDCl3) δ 6.83 (s, 2H), 3.22 (s, 3H), 3.12 (m, 4H), 2.44 (s, 3H), 2.26 (s, 3H), 2.01 (s, 6H), 1.35-1.42 (m, 2H), 1.1-1.25 (m, 2H), 1.00 (t, 3H), 0.90 (t, 3H) ppm. The mixture was quenched with water extracted with ethyl acetate The organic layer was separated dried concentrated to give the crude material After silica gel column purification

Conditions: temp:160.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A mixture of (6-chloro-2,5-dimethyl-pyrimidin-4-yl)-methyl-(2,4,6-trimethylphenyl)-amine (200 mg) and N-butyl-ethylamine (0.3 ml) in 1 ml of DMSO was heated in oil bath of 160° C. for 15 hours. The mixture was quenched with water and extracted with ethyl acetate. The organic layer was separated, dried and concentrated to give the crude material. After silica gel column purification using chloroform as eluent, the title compound was obtained as an oil. 1H NMR (CDCl3) δ 6.83 (s, 2H), 3.22 (s, 3H), 3.12 (m, 4H), 2.44 (s, 3H), 2.26 (s, 3H), 2.01 (s, 6H), 1.35-1.42 (m, 2H), 1.1-1.25 (m, 2H), 1.00 (t, 3H), 0.90 (t, 3H) ppm. The mixture was quenched with water extracted with ethyl acetate The organic layer was separated dried concentrated to give the crude material After silica gel column purification