4-(dimethylamino)cyclohexan-1-ol

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

Procedure: Into a 50-mL round-bottom flask, was placed a solution of 4-(dimethylamino)cyclohexan-1-ol (127 mg, 0.89 mmol, 1.50 equiv) in N,N-dimethylformamide (15 mL). This was followed by the addition of sodium hydride (71 mg, 1.77 mmol, 3.00 equiv, 60%). The resulting solution was stirred for 30 minutes at 80° C. in an oil bath. 4-chlorothieno[2,3-b]pyridine (100 mg, 0.59 mmol, 1.00 equiv) was added to the mixture. The resulting solution was stirred for 3 h at 120° C. in an oil bath. The reaction was then quenched by the addition of 10 mL of ethanol. The resulting mixture was concentrated under vacuum. The residue was purified on a silica gel column with dichloromethane/methanol (10:1). The resulting product (50 mg) was further purified by Prep-HPLC with the following conditions: Column, SunFire Prep C18, 19*150 mm 5 um; mobile phase, CH3CN and water with 0.05% NH4HCO3 (3.0% water with 0.05% NH4HCO3 up to 3.0% in 1 min, up to 4.7.0% in 13 min, up to 100.0% in 2 min); Detector, uv 254/220 nm. This resulted in 9.6 mg (6%) of N,N-dimethyl-4-[thieno[2,3-b]pyridin-4-yloxy]cyclohexan-1-amine as a white solid. Into a 50-mL round-bottom flask, was placed The resulting solution was stirred for 3 h at 120° C. in an oil bath The reaction was then quenched by the addition of 10 mL of ethanol The resulting mixture was concentrated under vacuum The residue was purified on a silica gel column with dichloromethane/methanol (10:1) The resulting product (50 mg) was further purified by Prep-HPLC with the following conditions mobile phase, CH3CN and water with 0.05% NH4HCO3 (3.0% water with 0.05% NH4HCO3 up to 3.0% in 1 min up to 4.7.0% in 13 min up to 100.0% in 2 min) This resulted in 9.6 mg (6%) of N,N-dimethyl-4-[thieno[2,3-b]pyridin-4-yloxy]cyclohexan-1-amine as a white solid

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

Procedure: Into a 50-mL round-bottom flask, was placed a solution of 4-(dimethylamino)cyclohexan-1-ol (127 mg, 0.89 mmol, 1.50 equiv) in N,N-dimethylformamide (15 mL). This was followed by the addition of sodium hydride (71 mg, 1.77 mmol, 3.00 equiv, 60%). The resulting solution was stirred for 30 minutes at 80° C. in an oil bath. 4-chlorothieno[2,3-b]pyridine (100 mg, 0.59 mmol, 1.00 equiv) was added to the mixture. The resulting solution was stirred for 3 h at 120° C. in an oil bath. The reaction was then quenched by the addition of 10 mL of ethanol. The resulting mixture was concentrated under vacuum. The residue was purified on a silica gel column with dichloromethane/methanol (10:1). The resulting product (50 mg) was further purified by Prep-HPLC with the following conditions: Column, SunFire Prep C18, 19*150 mm 5 um; mobile phase, CH3CN and water with 0.05% NH4HCO3 (3.0% water with 0.05% NH4HCO3 up to 3.0% in 1 min, up to 4.7.0% in 13 min, up to 100.0% in 2 min); Detector, uv 254/220 nm. This resulted in 9.6 mg (6%) of N,N-dimethyl-4-[thieno[2,3-b]pyridin-4-yloxy]cyclohexan-1-amine as a white solid. Into a 50-mL round-bottom flask, was placed The resulting solution was stirred for 3 h at 120° C. in an oil bath The reaction was then quenched by the addition of 10 mL of ethanol The resulting mixture was concentrated under vacuum The residue was purified on a silica gel column with dichloromethane/methanol (10:1) The resulting product (50 mg) was further purified by Prep-HPLC with the following conditions mobile phase, CH3CN and water with 0.05% NH4HCO3 (3.0% water with 0.05% NH4HCO3 up to 3.0% in 1 min up to 4.7.0% in 13 min up to 100.0% in 2 min) This resulted in 9.6 mg (6%) of N,N-dimethyl-4-[thieno[2,3-b]pyridin-4-yloxy]cyclohexan-1-amine as a white solid

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

Procedure: Into a 50-mL round-bottom flask, was placed a solution of 4-(dimethylamino)cyclohexan-1-ol (127 mg, 0.89 mmol, 1.50 equiv) in N,N-dimethylformamide (15 mL). This was followed by the addition of sodium hydride (71 mg, 1.77 mmol, 3.00 equiv, 60%). The resulting solution was stirred for 30 minutes at 80° C. in an oil bath. 4-chlorothieno[2,3-b]pyridine (100 mg, 0.59 mmol, 1.00 equiv) was added to the mixture. The resulting solution was stirred for 3 h at 120° C. in an oil bath. The reaction was then quenched by the addition of 10 mL of ethanol. The resulting mixture was concentrated under vacuum. The residue was purified on a silica gel column with dichloromethane/methanol (10:1). The resulting product (50 mg) was further purified by Prep-HPLC with the following conditions: Column, SunFire Prep C18, 19*150 mm 5 um; mobile phase, CH3CN and water with 0.05% NH4HCO3 (3.0% water with 0.05% NH4HCO3 up to 3.0% in 1 min, up to 4.7.0% in 13 min, up to 100.0% in 2 min); Detector, uv 254/220 nm. This resulted in 9.6 mg (6%) of N,N-dimethyl-4-[thieno[2,3-b]pyridin-4-yloxy]cyclohexan-1-amine as a white solid. MS: (ES, m/z): 277.10 [M+H]+ 1 NMR (300 MHz, CD3OD, ppm): δ 1.49-1.69 (m, 4H), 2.06 (d, J=12.3 Hz, 2H), 2.34 (m, 9H), 4.60 (m, 1H), 7.01 (d, J=5.8 Hz, 1H), 7.38 (d, J=6.0 Hz, 1H), 7.52 (d, J=6.3 Hz, 1H), 8.36 (d, J=5.8 Hz, 1H). Into a 50-mL round-bottom flask, was placed The resulting solution was stirred for 3 h at 120° C. in an oil bath The reaction was then quenched by the addition of 10 mL of ethanol The resulting mixture was concentrated under vacuum The residue was purified on a silica gel column with dichloromethane/methanol (10:1) The resulting product (50 mg) was further purified by Prep-HPLC with the following conditions mobile phase, CH3CN and water with 0.05% NH4HCO3 (3.0% water with 0.05% NH4HCO3 up to 3.0% in 1 min up to 4.7.0% in 13 min up to 100.0% in 2 min) This resulted in 9.6 mg (6%) of N,N-dimethyl-4-[thieno[2,3-b]pyridin-4-yloxy]cyclohexan-1-amine as a white solid

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

Procedure: Into a 50-mL round-bottom flask, was placed a solution of 4-(dimethylamino)cyclohexan-1-ol (127 mg, 0.89 mmol, 1.50 equiv) in N,N-dimethylformamide (15 mL). This was followed by the addition of sodium hydride (71 mg, 1.77 mmol, 3.00 equiv, 60%). The resulting solution was stirred for 30 minutes at 80° C. in an oil bath. 4-chlorothieno[2,3-b]pyridine (100 mg, 0.59 mmol, 1.00 equiv) was added to the mixture. The resulting solution was stirred for 3 h at 120° C. in an oil bath. The reaction was then quenched by the addition of 10 mL of ethanol. The resulting mixture was concentrated under vacuum. The residue was purified on a silica gel column with dichloromethane/methanol (10:1). The resulting product (50 mg) was further purified by Prep-HPLC with the following conditions: Column, SunFire Prep C18, 19*150 mm 5 um; mobile phase, CH3CN and water with 0.05% NH4HCO3 (3.0% water with 0.05% NH4HCO3 up to 3.0% in 1 min, up to 4.7.0% in 13 min, up to 100.0% in 2 min); Detector, uv 254/220 nm. This resulted in 9.6 mg (6%) of N,N-dimethyl-4-[thieno[2,3-b]pyridin-4-yloxy]cyclohexan-1-amine as a white solid. MS: (ES, m/z): 277.10 [M+H]+ 1 NMR (300 MHz, CD3OD, ppm): δ 1.49-1.69 (m, 4H), 2.06 (d, J=12.3 Hz, 2H), 2.34 (m, 9H), 4.60 (m, 1H), 7.01 (d, J=5.8 Hz, 1H), 7.38 (d, J=6.0 Hz, 1H), 7.52 (d, J=6.3 Hz, 1H), 8.36 (d, J=5.8 Hz, 1H). Into a 50-mL round-bottom flask, was placed The resulting solution was stirred for 3 h at 120° C. in an oil bath The reaction was then quenched by the addition of 10 mL of ethanol The resulting mixture was concentrated under vacuum The residue was purified on a silica gel column with dichloromethane/methanol (10:1) The resulting product (50 mg) was further purified by Prep-HPLC with the following conditions mobile phase, CH3CN and water with 0.05% NH4HCO3 (3.0% water with 0.05% NH4HCO3 up to 3.0% in 1 min up to 4.7.0% in 13 min up to 100.0% in 2 min) This resulted in 9.6 mg (6%) of N,N-dimethyl-4-[thieno[2,3-b]pyridin-4-yloxy]cyclohexan-1-amine as a white solid

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

Procedure: To a solution of tert-butyl N-(2-[4-chlorothieno[2,3-d]pyrimidin-6-yl]ethyl)carbamate (100 mg, 0.32 mmol, 1.00 equiv) in freshly distilled THF (20 mL) was added sodium hydride (64 mg, 1.6 mmol, 5.0 equiv, 60% dispersion in mineral oil) at 0° C. under nitrogen. After stirring for 30 min at room temperature, a solution of 4-(dimethylamino)cyclohexan-1-ol (50 mg, 0.35 mmol, 1.06 equiv) was added and stirred overnight at room temperature. The reaction was then quenched by the addition of brine and extracted with EtOAc. The organic layers was combined and dried over anhydrous sodium sulfate. After filtration and concentration, the residue was applied onto a silica gel column with DCM/MeOH (50:1-30:1) to provide 70 mg (52%) of tert-butyl N-[2-(4-[[4-(dimethylamino)cyclohexyl]oxy]thieno[2,3-d]pyrimidin-6-yl)ethyl]carbamate as a light yellow solid. MS (ES): m/z 421 (M+H)+. stirred overnight at room temperature The reaction was then quenched by the addition of brine extracted with EtOAc dried over anhydrous sodium sulfate After filtration and concentration

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

Procedure: Into a 50-mL round-bottom flask, was placed a solution of 4-(dimethylamino)cyclohexan-1-ol (127 mg, 0.89 mmol, 1.50 equiv) in N,N-dimethylformamide (15 mL). This was followed by the addition of sodium hydride (71 mg, 1.77 mmol, 3.00 equiv, 60%). The resulting solution was stirred for 30 minutes at 80° C. in an oil bath. 4-chlorothieno[2,3-b]pyridine (100 mg, 0.59 mmol, 1.00 equiv) was added to the mixture. The resulting solution was stirred for 3 h at 120° C. in an oil bath. The reaction was then quenched by the addition of 10 mL of ethanol. The resulting mixture was concentrated under vacuum. The residue was purified on a silica gel column with dichloromethane/methanol (10:1). The resulting product (50 mg) was further purified by Prep-HPLC with the following conditions: Column, SunFire Prep C18, 19*150 mm 5 um; mobile phase, CH3CN and water with 0.05% NH4HCO3 (3.0% water with 0.05% NH4HCO3 up to 3.0% in 1 min, up to 4.7.0% in 13 min, up to 100.0% in 2 min); Detector, uv 254/220 nm. This resulted in 9.6 mg (6%) of N,N-dimethyl-4-[thieno[2,3-b]pyridin-4-yloxy]cyclohexan-1-amine as a white solid. Into a 50-mL round-bottom flask, was placed The resulting solution was stirred for 3 h at 120° C. in an oil bath The reaction was then quenched by the addition of 10 mL of ethanol The resulting mixture was concentrated under vacuum The residue was purified on a silica gel column with dichloromethane/methanol (10:1) The resulting product (50 mg) was further purified by Prep-HPLC with the following conditions mobile phase, CH3CN and water with 0.05% NH4HCO3 (3.0% water with 0.05% NH4HCO3 up to 3.0% in 1 min up to 4.7.0% in 13 min up to 100.0% in 2 min) This resulted in 9.6 mg (6%) of N,N-dimethyl-4-[thieno[2,3-b]pyridin-4-yloxy]cyclohexan-1-amine as a white solid