(2S)-2-amino-2-cyclohexylethanol

Conditions: temp:50.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Diphosgene (0.704 mL, 6.05 mmol) was added dropwise to a stirred suspension of (S)-2-amino-2-cyclohexylethanol (1.02 g, 7.12 mmol), Et3N (6.95 mL, 49.9 mmol) and activated charcoal (40 mg) in THF (20 mL) at 0° C. under N2. The reaction mixture was heated at 50° C. overnight. After cooling, the suspension was filtered through Celite. To the filtrate was added sat. aq. NaHCO3 solution. The mixture was extracted with EtOAc. The combined organic layers were washed with brine, dried and concentrated. The residue was purified by silica gel flash column chromatography (1:1 hexane/EtOAc) to give (S)-4-cyclohexyloxazolidin-2-one (0.900 g, 75%) as a white solid. After cooling the suspension was filtered through Celite To the filtrate was added sat. aq. NaHCO3 solution The mixture was extracted with EtOAc The combined organic layers were washed with brine dried concentrated The residue was purified by silica gel flash column chromatography (1:1 hexane/EtOAc)

Conditions: temp:50.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Diphosgene (0.704 mL, 6.05 mmol) was added dropwise to a stirred suspension of (S)-2-amino-2-cyclohexylethanol (1.02 g, 7.12 mmol), Et3N (6.95 mL, 49.9 mmol) and activated charcoal (40 mg) in THF (20 mL) at 0° C. under N2. The reaction mixture was heated at 50° C. overnight. After cooling, the suspension was filtered through Celite. To the filtrate was added sat. aq. NaHCO3 solution. The mixture was extracted with EtOAc. The combined organic layers were washed with brine, dried and concentrated. The residue was purified by silica gel flash column chromatography (1:1 hexane/EtOAc) to give (S)-4-cyclohexyloxazolidin-2-one (0.900 g, 75%) as a white solid. After cooling the suspension was filtered through Celite To the filtrate was added sat. aq. NaHCO3 solution The mixture was extracted with EtOAc The combined organic layers were washed with brine dried concentrated The residue was purified by silica gel flash column chromatography (1:1 hexane/EtOAc)

Conditions: temp:150.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A 4:1 mixture of 6-((3H-imidazo[4,5-b]pyridin-3-yl)methyl)-2-(methylsulfinyl)benzo[d]thiazole and 6-((3H-imidazo[4,5-b]pyridin-3-yl)methyl)-2-(methylsulfonyl)benzo[d]thiazole (60 mg) from Step 2 of this Example was dissolved in anhydrous DMA (1.5 mL) and to this solution were added (S)-2-amino-2-cyclohexylethanol (52 mg, 0.366 mmol) from Step 3 of this Example and DIEA (94 mg, 0.732 mmol). The reaction vessel was sealed and the mixture was heated in a Biotage microwave synthesizer at 150° C. for 30 min. LCMS analysis indicated that the reaction was not complete. To the reaction mixture was added additional (S)-2-amino-2-cyclohexylethanol (52 mg, 0.366 mmol). The reaction vessel was sealed and the mixture was heated in a Biotage microwave synthesizer at 150° C. for 40 min. After cooling to rt, the mixture was purified directly by reverse-phase HPLC using a mixture of water (5% CH3CN, 0.05% HCOOH) and CH3CN (0.05% HCOOH) as the mobile phase and Varian Pursuit XRs C-18 column as the stationary phase to afford (S)-2-((6-((3H-imidazo[4,5-b]pyridin-3-yl)methyl)benzo[d]thiazol-2-yl)amino)-2-cyclohexylethanol (4 mg) as a white solid. 1H NMR (500 MHz, DMSO-d6) δ 8.58 (s, 1H), 8.37 (m, 1H), 8.08 (m, 1H), 7.84 (d, J=8.9 Hz, 1H), 7.66 (s, 1H), 7.18-7.31 (m, 3H), 5.48 (s, 2H), 3.71 (m, 1H), 3.50 (m, 1H), 1.54-1.77 (m, 7H), 0.95-1.24 (m, 6H). LCMS (ESI) m/z 408 (M+H)+. The reaction vessel was sealed The reaction vessel was sealed the mixture was heated in a Biotage microwave synthesizer at 150° C. for 40 min After cooling to rt the mixture was purified directly by reverse-phase a mixture of water (5% CH3CN, 0.05% HCOOH) and CH3CN (0.05% HCOOH) as the mobile phase and Varian Pursuit XRs C-18 column as the stationary phase

Conditions: temp:80.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a stirred mixture of LiAlH4 (724 mg, 19.08 mmol) in anhydrous THF (20 mL) at rt was added portionwise L-(+)-2-cyclohexylglycine (1 g, 6.36 mmol). The mixture was heated at 80° C. for 4 h. The mixture was cooled to 0° C. and then water (1 mL), 1M aq NaOH (1 mL), and water (3 mL) were added sequentially. The mixture was filtered and the filtrate was partitioned between a mixture of DCM, 1M aq NaOH, and saturated aq sodium potassium tartrate. The organic layer was separated and further washed with 1M aq NaOH. The organic layer was separated, dried over MgSO4, filtered, and concentrated under reduced pressure to afford (S)-2-amino-2-cyclohexylethanol (500 mg) which was not purified further. LCMS (ESI) m/z 144 (M+H)+. The mixture was cooled to 0° C. The mixture was filtered the filtrate was partitioned between a mixture of DCM, 1M aq NaOH, and saturated aq sodium potassium tartrate The organic layer was separated further washed with 1M aq NaOH The organic layer was separated dried over MgSO4 filtered concentrated under reduced pressure

Conditions: temp:50.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Diphosgene (0.704 mL, 6.05 mmol) was added dropwise to a stirred suspension of (S)-2-amino-2-cyclohexylethanol (1.02 g, 7.12 mmol), Et3N (6.95 mL, 49.9 mmol) and activated charcoal (40 mg) in THF (20 mL) at 0° C. under N2. The reaction mixture was heated at 50° C. overnight. After cooling, the suspension was filtered through Celite. To the filtrate was added sat. aq. NaHCO3 solution. The mixture was extracted with EtOAc. The combined organic layers were washed with brine, dried and concentrated. The residue was purified by silica gel flash column chromatography (1:1 hexane/EtOAc) to give (S)-4-cyclohexyloxazolidin-2-one (0.900 g, 75%) as a white solid. After cooling the suspension was filtered through Celite To the filtrate was added sat. aq. NaHCO3 solution The mixture was extracted with EtOAc The combined organic layers were washed with brine dried concentrated The residue was purified by silica gel flash column chromatography (1:1 hexane/EtOAc)