(2S)-2-amino-2-(4-chloro-3-fluorophenyl)ethanol;hydrochloride

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

Procedure: 3-((3S,4S)-3-Fluoro-tetrahydro-pyran-4-ylamino)-isoquinoline-6-carboxylic acid [(S)-1-(4-chloro-3-fluoro-phenyl)-2-hydroxy-ethyl]-amide (II-54) was prepared analogously except in step 2, (S)-2-aminopropan-1-ol was replaced with (3S,4S)-3-fluorotetrahydro-2H-pyran-4-amine (71c) and in step 5, 50c was replaced with (S)-2-amino-2-(4-chloro-3-fluoro-phenyl)ethanol hydrochloride (62e). 1H NMR (500 MHz, MeOH-d4): δ 8.90 (s, 1H), 8.09 (s, 1H), 7.92-7.88 (m, 1H), 7.61-7.59 (m, 1H), 7.47-7.45 (m, 1H), 7.38-7.33 (m, 1H), 7.28-7.24 (m, 1H), 6.91 (d, J=9.0 Hz, 1H), 5.21 (t, J=6.5 Hz, 1H), 4.84-4.73 (m, 1H), 4.27-4.11 (m, 2H), 4.05-4.02 (m, 1H), 3.92-3.80 (m, 2H), 3.75-3.60 (m, 2H), 2.06-1.96 (m, 1H), 1.93-1.88 (m, 1H).

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

Procedure: 3-((3S,4S)-3-Fluoro-tetrahydro-pyran-4-ylamino)-isoquinoline-6-carboxylic acid [(S)-1-(4-chloro-3-fluoro-phenyl)-2-hydroxy-ethyl]-amide (II-54) was prepared analogously except in step 2, (S)-2-aminopropan-1-ol was replaced with (3S,4S)-3-fluorotetrahydro-2H-pyran-4-amine (71c) and in step 5, 50c was replaced with (S)-2-amino-2-(4-chloro-3-fluoro-phenyl)ethanol hydrochloride (62e). 1H NMR (500 MHz, MeOH-d4): δ 8.90 (s, 1H), 8.09 (s, 1H), 7.92-7.88 (m, 1H), 7.61-7.59 (m, 1H), 7.47-7.45 (m, 1H), 7.38-7.33 (m, 1H), 7.28-7.24 (m, 1H), 6.91 (d, J=9.0 Hz, 1H), 5.21 (t, J=6.5 Hz, 1H), 4.84-4.73 (m, 1H), 4.27-4.11 (m, 2H), 4.05-4.02 (m, 1H), 3.92-3.80 (m, 2H), 3.75-3.60 (m, 2H), 2.06-1.96 (m, 1H), 1.93-1.88 (m, 1H).

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

Procedure: 3-(Tetrahydro-pyran-4-ylamino)-isoquinoline-6-carboxylic acid [(S)-1-(4-chloro-3-fluoro-phenyl)-2-hydroxy-ethyl]-amide (II-12) was prepared analogously except in step 2, (S)-2-aminopropan-1-ol was replaced with 4-amino-tetrahydropyran and in step 5, 50c was replaced with (S)-2-amino-2-(4-chloro-3-fluoro-phenyl)ethanol hydrochloride (62e). 1H NMR (400 MHz, DMSO-d6) δ 8.91 (s, 1H), 8.83 (d, J=7.9 Hz, 1H), 8.10 (s, 1H), 7.85 (d, J=8.6 Hz, 1H), 7.55 (t, J=8.1 Hz, 1H), 7.53 (dd, J=8.6, 1.6 Hz, 1H), 7.47 (dd, J=10.6, 1.8 Hz, 1H), 7.29 (dd, J=8.3, 1.7 Hz, 1H), 6.74 (s, 1H), 6.53 (d, J=7.9 Hz, 1H), 5.10 (q, J=7.1 Hz, 1H), 5.03 (t, J=5.8 Hz, 1H), 3.94-3.87 (m, 2H), 3.87-3.78 (m, 1H), 3.78-3.64 (m, 2H), 3.45 (td, J=11.5, 2.0 Hz, 2H), 1.92 (d, J=12.4 Hz, 2H), 1.56-1.43 (m, 2H).

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

Procedure: 3-((3S,4S)-3-Fluoro-tetrahydro-pyran-4-ylamino)-isoquinoline-6-carboxylic acid [(S)-1-(4-chloro-3-fluoro-phenyl)-2-hydroxy-ethyl]-amide (II-54) was prepared analogously except in step 2, (S)-2-aminopropan-1-ol was replaced with (3S,4S)-3-fluorotetrahydro-2H-pyran-4-amine (71c) and in step 5, 50c was replaced with (S)-2-amino-2-(4-chloro-3-fluoro-phenyl)ethanol hydrochloride (62e). 1H NMR (500 MHz, MeOH-d4): δ 8.90 (s, 1H), 8.09 (s, 1H), 7.92-7.88 (m, 1H), 7.61-7.59 (m, 1H), 7.47-7.45 (m, 1H), 7.38-7.33 (m, 1H), 7.28-7.24 (m, 1H), 6.91 (d, J=9.0 Hz, 1H), 5.21 (t, J=6.5 Hz, 1H), 4.84-4.73 (m, 1H), 4.27-4.11 (m, 2H), 4.05-4.02 (m, 1H), 3.92-3.80 (m, 2H), 3.75-3.60 (m, 2H), 2.06-1.96 (m, 1H), 1.93-1.88 (m, 1H).

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

Procedure: 3-(Tetrahydro-pyran-4-ylamino)-isoquinoline-6-carboxylic acid [(S)-1-(4-chloro-3-fluoro-phenyl)-2-hydroxy-ethyl]-amide (II-12) was prepared analogously except in step 2, (S)-2-aminopropan-1-ol was replaced with 4-amino-tetrahydropyran and in step 5, 50c was replaced with (S)-2-amino-2-(4-chloro-3-fluoro-phenyl)ethanol hydrochloride (62e). 1H NMR (400 MHz, DMSO-d6) δ 8.91 (s, 1H), 8.83 (d, J=7.9 Hz, 1H), 8.10 (s, 1H), 7.85 (d, J=8.6 Hz, 1H), 7.55 (t, J=8.1 Hz, 1H), 7.53 (dd, J=8.6, 1.6 Hz, 1H), 7.47 (dd, J=10.6, 1.8 Hz, 1H), 7.29 (dd, J=8.3, 1.7 Hz, 1H), 6.74 (s, 1H), 6.53 (d, J=7.9 Hz, 1H), 5.10 (q, J=7.1 Hz, 1H), 5.03 (t, J=5.8 Hz, 1H), 3.94-3.87 (m, 2H), 3.87-3.78 (m, 1H), 3.78-3.64 (m, 2H), 3.45 (td, J=11.5, 2.0 Hz, 2H), 1.92 (d, J=12.4 Hz, 2H), 1.56-1.43 (m, 2H).