(1S)-1-(4-fluorophenyl)ethanamine

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

Procedure: A mixture of 5-cyclopropyl-N-(2,3,4-trifluoro-6-nitrophenyl)-1H-pyrazol-3-amine (Method 103, 0.300 g, 1.01 mmol), (S)-1-(4-fluorophenyl)ethylamine (0.154 g, 1.11 mmol) and DIEA (0.263 ml, 1.51 mmol) in n-BuOH (2 ml) was heated in a sealed tube placed in an oil bath set at 135° C. for 8 hours. The solvent was removed under reduced pressure and the residue was purified by chromatography (hexane-EtOAc=3:1) to give the title compound as an orange solid (0.30 g, 71%). 1H NMR (400 MHz) 11.89 (s, 1H), 8.57 (s, 1H), 7.69 (d, 1H, J=13.6 Hz), 7.35 (m, 2H), 7.14 (t, J=8.8 Hz, 2H), 6.81 (d, 1H, 7.6 Hz), 5.39 (s, 1H), 5.00 (m, 1H), 1.80 (m, 1H), 1.49 (d, J=6.8 Hz, 3H), 0.90 (m, 2H), 0.62 (m, 2H). MS: Calcd.: 417; Found: [M+H]+ 418. was heated in a sealed tube placed in an oil bath The solvent was removed under reduced pressure the residue was purified by chromatography (hexane-EtOAc=3:1)

Conditions: temp:230.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A mixture of 3-(5-cyclopropyl-1H-pyrazol-3-ylamino)-5-fluoro-2-nitrobenzonitrile (Method 98, 3.50 g, 12.2 mmol), (S)-1-(4-fluoro-phenyl)ethylamine (1.87 g, 13.4 mmol), and DIEA (2.6 ml, 14.6 mmol) in n-BuOH (20 ml) was heated in a sealed tube at 230° C. for 2 hours. The solvent was removed under reduced pressure and the residue was purified by column chromatography (hexane-EtOAc=1:2) to give the title compound as a yellow solid (4.4 g, 89%). 1H NMR (400 MHz) 12.38 (s, 1H), 10.12 (b, 1H), 8.07 (d, J=6.4 Hz, 1H), 7.34 (m, 2H), 7.16 (m, 2H), 6.89 (b, 1H), 6.77 (s, 1H), 5.63 (m, 1H), 4.55 (m, 1H), 1.90 (m, 1H), 1.45 (d, J=6.8 Hz, 3H), 0.97 (m, 2H), 0.70 (m 2H). MS: Calcd.: 406; Found: [M+H]+ 407. The solvent was removed under reduced pressure the residue was purified by column chromatography (hexane-EtOAc=1:2)

Conditions: temp:230.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A mixture of 3-(5-cyclopropyl-1H-pyrazol-3-ylamino)-5-fluoro-2-nitrobenzonitrile (Method 98, 3.50 g, 12.2 mmol), (S)-1-(4-fluoro-phenyl)ethylamine (1.87 g, 13.4 mmol), and DIEA (2.6 ml, 14.6 mmol) in n-BuOH (20 ml) was heated in a sealed tube at 230° C. for 2 hours. The solvent was removed under reduced pressure and the residue was purified by column chromatography (hexane-EtOAc=1:2) to give the title compound as a yellow solid (4.4 g, 89%). 1H NMR (400 MHz) 12.38 (s, 1H), 10.12 (b, 1H), 8.07 (d, J=6.4 Hz, 1H), 7.34 (m, 2H), 7.16 (m, 2H), 6.89 (b, 1H), 6.77 (s, 1H), 5.63 (m, 1H), 4.55 (m, 1H), 1.90 (m, 1H), 1.45 (d, J=6.8 Hz, 3H), 0.97 (m, 2H), 0.70 (m 2H). MS: Calcd.: 406; Found: [M+H]+ 407. The solvent was removed under reduced pressure the residue was purified by column chromatography (hexane-EtOAc=1:2)

Conditions: temp:180.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A mixture of 2-chloro-N-(5-cyclopropyl-1H-pyrazol-3-yl)-5-nitropyridin-4-amine (Method 90, 0.15 g, 0.54 mmol), (S)-1-(4-fluoro-phenyl)-ethylamine (0.093 g, 0.67 mmol), and DIEA (0.12 ml, 0.67 mmol) in n-BuOH (5 ml) was heated in a sealed tube at 180° C. for 32 hours. The solvent was removed under reduced pressure and the residue was purified by column chromatography (hexane-EtOAc=1:1) to give the title compound as a yellow solid (0.168 g, 82%). 1H NMR (400 MHz) 12.37 (s, 1H), 9.59 (b, 1H), 8.83 (s, 1H), 8.20 (b, 1H), 7.37 (m, 2H), 7.13 (m, 2H), 6.69 (b, 1H), 5.88 (b, 1H), 5.29 (m, 1H), 1.91 (m, 1H), 1.43 (d, J=6.4 Hz, 3H), 0.97 (m, 2H), 0.71 (m 2H). MS: Calcd.: 382; Found: [M+H]+ 383. The solvent was removed under reduced pressure the residue was purified by column chromatography (hexane-EtOAc=1:1)

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

Procedure: A mixture of 5-cyclopropyl-N-(4,5-difluoro-2-nitrophenyl)-1H-pyrazol-3-amine (Method 86; 0.300 g, 1.07 mmol), (S)-1-(4-fluoro-phenyl)ethylamine (0.164 g, 1.18 mmol), and DIEA (0.280 ml, 1.61 mmol) in n-BuOH (2 ml) was heated in a sealed tube at 160° C. for 16 hrs. The solvent was removed under reduced pressure and the residue was purified by column chromatography (hexane:EtOAc=3:1) to give the title compound as an orange solid (0.360 g, 84%). NMR (400 MHz) 12.29 (s, 1H), 10.14 (s, 1H), 7.75 (d, J=12.8 Hz, 1H), 7.63 (d, J=6.4 Hz, 1H), 7.41 (m, 2H), 7.14 (t, J=8.8 Hz, 2H), 7.00 (d, J=8.0 Hz, 1H), 5.63 (s, 1H), 4.55 (m, 1H), 1.90 (m, 1H), 1.52 (d, J=6.8 Hz, 3H), 0.98 (m, 2H), 0.71 (m, 2H). MS: Calcd.: 399; Found: [M+H]+ 400. The solvent was removed under reduced pressure the residue was purified by column chromatography (hexane:EtOAc=3:1)

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

Procedure: A mixture of 5-cyclopropyl-N-(4,5-difluoro-2-nitrophenyl)-1H-pyrazol-3-amine (Method 86; 0.300 g, 1.07 mmol), (S)-1-(4-fluoro-phenyl)ethylamine (0.164 g, 1.18 mmol), and DIEA (0.280 ml, 1.61 mmol) in n-BuOH (2 ml) was heated in a sealed tube at 160° C. for 16 hrs. The solvent was removed under reduced pressure and the residue was purified by column chromatography (hexane:EtOAc=3:1) to give the title compound as an orange solid (0.360 g, 84%). NMR (400 MHz) 12.29 (s, 1H), 10.14 (s, 1H), 7.75 (d, J=12.8 Hz, 1H), 7.63 (d, J=6.4 Hz, 1H), 7.41 (m, 2H), 7.14 (t, J=8.8 Hz, 2H), 7.00 (d, J=8.0 Hz, 1H), 5.63 (s, 1H), 4.55 (m, 1H), 1.90 (m, 1H), 1.52 (d, J=6.8 Hz, 3H), 0.98 (m, 2H), 0.71 (m, 2H). MS: Calcd.: 399; Found: [M+H]+ 400. The solvent was removed under reduced pressure the residue was purified by column chromatography (hexane:EtOAc=3:1)

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

Procedure: A mixture of 5-cyclopropyl-N-(2,3-difluoro-6-nitrophenyl)-1H-pyrazol-3-amine (Method 85; 0.400 g, 1.43 mmol), (S)-1-(4-fluoro-phenyl)ethylamine (0.209 g, 1.50 mmol, and DIEA (0.373 ml, 2.14 mmol) in n-BuOH (3 ml) was heated in a sealed tube at 160° C. for 8 hours. The solvent was removed under reduced pressure and the residue was purified by column chromatography (hexane:EtOAc=4:1) to give the title compound as an orange solid (0.40 g, 70%). NMR (400 MHz) 11.95 (s, 1H), 8.74 (s, 1H), 7.72 (d, J=9.2 Hz, 1H), 7.43 (t, J=7.0 Hz, 2H), 7.25 (d, J=6.4 Hz, 1H), 7.15 (t, J=8.8 Hz, 2H), 6.26 (t, J=8.6 Hz, 1H), 5.63 (s, 1H), 4.78 (m, 1H), 1.84 (m, 1H), 1.48 (d, J=6.8 Hz, 3H), 0.91 (m, 2H), 0.66 (m, 2H). MS: Calcd.: 399; Found: [M+H]+ 400. The solvent was removed under reduced pressure the residue was purified by column chromatography (hexane:EtOAc=4:1)

Conditions: temp:230.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A mixture of 5-cyclopropyl-N-(5-fluoro-2-nitrophenyl)-1H-pyrazol-3-amine (Method 82; 0.27 g, 1.03 mmol), (S)-1-(4-fluoro-phenyl)-ethylamine (0.72 g, 5.15 mmol), and DIEA (0.27 ml, 1.54 mmol) in n-BuOH (5 ml) was heated in a sealed tube at 230° C. for 23 hours. The solvent was removed under reduced pressure and the residue was purified by column chromatography (hexane:EtOAc=1:2) to give the title compound as a yellow solid (0.38 g, 97%). NMR (400 MHz) 12.25 (s, 1H), 10.14 (s, 1H), 7.87 (d, J=9.6 Hz, 1H), 7.76 (d, J=6.4 Hz, 1H), 7.36 (m, 2H), 7.15 (m, 2H), 6.68 (s, 1H), 6.22 (d, J=8.4 Hz, 1H), 5.60 (br, 1H), 4.57 (m, 1H), 1.87 (m, 1H), 1.44 (d, J=6.8 Hz, 3H), 0.98 (m, 2H), 0.70 (m 2H). MS: Calcd.: 381; Found: [M+H]+ 382. The solvent was removed under reduced pressure the residue was purified by column chromatography (hexane:EtOAc=1:2)

Conditions: temp:165.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A mixture of 6-chloro-N-(5-cyclopropyl-1H-pyrazol-3-yl)-3-nitropyridin-2-amine (Method 77; 0.30 g, 1.07 mmol), (S)-1-(4-fluoro-phenyl)ethylamine (0.23 g, 1.61 mmol), and DIEA (0.23 ml, 1.34 mmol) in n-BuOH (5 ml) was heated in a sealed tube at 165° C. for 18 hours. The solvent was removed under reduced pressure and the residue was purified by column chromatography (hexane:EtOAc=1:1) to give the title compound as a yellow solid (0.41 g, 99%). NMR (400 MHz) 12.22 (s, 1H), 10.98 (s, 1H), 8.70 (d, J=7.2 Hz, 1H), 8.10 (d, J=9.2 Hz, 1H), 7.39 (m, 2H), 7.18 (m, 2H), 6.22 (d, J=9.2 Hz, 1H), 6.17 (s, 1H), 5.27 (m, 1H), 1.89 (m, 1H), 1.52 (d, J=6.4 Hz, 3H), 0.95 (m, 2H), 0.64 (m 2H). MS: Calcd.: 382; Found: [M+H]+ 383. The solvent was removed under reduced pressure the residue was purified by column chromatography (hexane:EtOAc=1:1)

Conditions: temp:165.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A mixture of 6-chloro-N-(5-cyclopropyl-1H-pyrazol-3-yl)-3-nitropyridin-2-amine (Method 77; 0.30 g, 1.07 mmol), (S)-1-(4-fluoro-phenyl)ethylamine (0.23 g, 1.61 mmol), and DIEA (0.23 ml, 1.34 mmol) in n-BuOH (5 ml) was heated in a sealed tube at 165° C. for 18 hours. The solvent was removed under reduced pressure and the residue was purified by column chromatography (hexane:EtOAc=1:1) to give the title compound as a yellow solid (0.41 g, 99%). NMR (400 MHz) 12.22 (s, 1H), 10.98 (s, 1H), 8.70 (d, J=7.2 Hz, 1H), 8.10 (d, J=9.2 Hz, 1H), 7.39 (m, 2H), 7.18 (m, 2H), 6.22 (d, J=9.2 Hz, 1H), 6.17 (s, 1H), 5.27 (m, 1H), 1.89 (m, 1H), 1.52 (d, J=6.4 Hz, 3H), 0.95 (m, 2H), 0.64 (m 2H). MS: Calcd.: 382; Found: [M+H]+ 383. The solvent was removed under reduced pressure the residue was purified by column chromatography (hexane:EtOAc=1:1)

Conditions: temp:25.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A mixture of 2-chloro-N-(5-cyclopropyl-1H-pyrazol-3-yl)-5-nitropyrimidin-4-amine (Method 76; 1.0 g, 3.6 mmol), (S)-1-(4-fluorophenyl)ethanamine (0.5 g, 3.6 mmol), and DIEA (0.6 g, 4.6 mmol) in n-BuOH (15 ml) was stirred at 25° C. for 1 hour and then concentrated. The resulting oil was purified by column chromatography (DCM:MeOH=50:1) to give the title compound (0.8 g, 60%). MS: Calcd.: 383; Found: [M+H]+ 384. concentrated The resulting oil was purified by column chromatography (DCM:MeOH=50:1)

Conditions: temp:25.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A mixture of 2-chloro-N-(5-cyclopropyl-1H-pyrazol-3-yl)-5-nitropyrimidin-4-amine (Method 76; 1.0 g, 3.6 mmol), (S)-1-(4-fluorophenyl)ethanamine (0.5 g, 3.6 mmol), and DIEA (0.6 g, 4.6 mmol) in n-BuOH (15 ml) was stirred at 25° C. for 1 hour and then concentrated. The resulting oil was purified by column chromatography (DCM:MeOH=50:1) to give the title compound (0.8 g, 60%). MS: Calcd.: 383; Found: [M+H]+ 384. concentrated The resulting oil was purified by column chromatography (DCM:MeOH=50:1)