(S)-(+)-2-氯-1-丙醇

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: Synthesized as described in Example 4 using 2-methyl-4-(trifluoromethyl)-1H-indole-5-carbonitrile (Example 120) and (2S)-2-chloro-1-propanol: MS (ES) m/z 283 (M+1). Synthesized

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: Synthesized as described in Example 4 using 2-methyl-4-(trifluoromethyl)-1H-indole-5-carbonitrile (Example 120) and (2S)-2-chloro-1-propanol: MS (ES) m/z 283 (M+1). Synthesized

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: To a solution of 4-{[(1S,2S)-2-(5-methoxypyridin-2-yl)cyclopropyl]methoxy}-2-methyl-5-(1H-pyrazol-4-yl)pyrimidine (NN1) (15 mg, 0.04 mmol) in DMF (0.4 mL) was added and (2S)-2-chloropropan-1-ol (9.0 mg, 0.09 mmol) and potassium carbonate (18.4 mg, 0.13 mmol). The reaction mixture was stirred at ambient temperature for 14 hours. The mixture was filtered and purified by reverse phase chromatography (Waters Sunfire Prep C18 OBD, 5-45% acetonitrile in water with 0.1% TFA modifier) to afford the title compound as a white solid. 1H NMR (500 MHz, DMSO): δ 8.74 (s, 1 H), 8.13 (d, J=11.7 Hz, 2 H), 8.00 (s, 1 H), 7.27 (d, J=7.1 Hz, 2 H), 4.55-4.50 (m, 1 H), 4.37-4.30 (m, 1 H), 3.96 (s, 3 H), 3.78 (s, 3 H), 2.50 (s, 3 H), 2.22 (d, J=7.1 Hz, 1 H), 1.80 (s, 1 H), 1.25-1.16 (m, 2 H), 1.07 (m, 1 H), 1.01 (d, J=5.3 Hz, 3 H); HRMS m/z (M+H) 396.2019 found, 396.2030 required. The mixture was filtered purified by reverse phase chromatography (Waters Sunfire Prep C18 OBD, 5-45% acetonitrile in water with 0.1% TFA modifier)

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: To a solution of 4-{[(1S,2S)-2-(5-methoxypyridin-2-yl)cyclopropyl]methoxy}-2-methyl-5-(1H-pyrazol-4-yl)pyrimidine (NN1) (15 mg, 0.04 mmol) in DMF (0.4 mL) was added and (2S)-2-chloropropan-1-ol (9.0 mg, 0.09 mmol) and potassium carbonate (18.4 mg, 0.13 mmol). The reaction mixture was stirred at ambient temperature for 14 hours. The mixture was filtered and purified by reverse phase chromatography (Waters Sunfire Prep C18 OBD, 5-45% acetonitrile in water with 0.1% TFA modifier) to afford the title compound as a white solid. 1H NMR (500 MHz, DMSO): δ 8.74 (s, 1 H), 8.13 (d, J=11.7 Hz, 2 H), 8.00 (s, 1 H), 7.27 (d, J=7.1 Hz, 2 H), 4.55-4.50 (m, 1 H), 4.37-4.30 (m, 1 H), 3.96 (s, 3 H), 3.78 (s, 3 H), 2.50 (s, 3 H), 2.22 (d, J=7.1 Hz, 1 H), 1.80 (s, 1 H), 1.25-1.16 (m, 2 H), 1.07 (m, 1 H), 1.01 (d, J=5.3 Hz, 3 H); HRMS m/z (M+H) 396.2019 found, 396.2030 required. The mixture was filtered purified by reverse phase chromatography (Waters Sunfire Prep C18 OBD, 5-45% acetonitrile in water with 0.1% TFA modifier)

反应条件: temp:130.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: Under argon, 785 mg (6.43 mmol) of 4-hydroxybenzaldehyde and 759 mg (8.04 mmol) of (S)-(+)-2-chloro-1-propanol were initially charged in 15.7 ml of DMF. 2.04 g (19.3 mmol) of sodium carbonate were added, and the mixture was then stirred at 130° C. for 20 h. The reaction mixture was purified by preparative HPLC (Chromasil, water/acetonitrile). The reaction mixture was purified by preparative HPLC (Chromasil, water/acetonitrile)

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: Synthesized as described in Example 4 using 2-methyl-4-(trifluoromethyl)-1H-indole-5-carbonitrile (Example 120) and (2S)-2-chloro-1-propanol: MS (ES) m/z 283 (M+1). Synthesized

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: Synthesized as described in Example 4 using 2-methyl-4-(trifluoromethyl)-1H-indole-5-carbonitrile (Example 120) and (2S)-2-chloro-1-propanol: MS (ES) m/z 283 (M+1). Synthesized

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: Synthesized as described in Example 4 using 2-methyl-4-(trifluoromethyl)-1H-indole-5-carbonitrile (Example 120) and (2S)-2-chloro-1-propanol: MS (ES) m/z 283 (M+1). Synthesized

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: To a solution of 4-{[(1S,2S)-2-(5-methoxypyridin-2-yl)cyclopropyl]methoxy}-2-methyl-5-(1H-pyrazol-4-yl)pyrimidine (NN1) (15 mg, 0.04 mmol) in DMF (0.4 mL) was added and (2S)-2-chloropropan-1-ol (9.0 mg, 0.09 mmol) and potassium carbonate (18.4 mg, 0.13 mmol). The reaction mixture was stirred at ambient temperature for 14 hours. The mixture was filtered and purified by reverse phase chromatography (Waters Sunfire Prep C18 OBD, 5-45% acetonitrile in water with 0.1% TFA modifier) to afford the title compound as a white solid. 1H NMR (500 MHz, DMSO): δ 8.74 (s, 1 H), 8.13 (d, J=11.7 Hz, 2 H), 8.00 (s, 1 H), 7.27 (d, J=7.1 Hz, 2 H), 4.55-4.50 (m, 1 H), 4.37-4.30 (m, 1 H), 3.96 (s, 3 H), 3.78 (s, 3 H), 2.50 (s, 3 H), 2.22 (d, J=7.1 Hz, 1 H), 1.80 (s, 1 H), 1.25-1.16 (m, 2 H), 1.07 (m, 1 H), 1.01 (d, J=5.3 Hz, 3 H); HRMS m/z (M+H) 396.2019 found, 396.2030 required. The mixture was filtered purified by reverse phase chromatography (Waters Sunfire Prep C18 OBD, 5-45% acetonitrile in water with 0.1% TFA modifier)

反应条件: temp:130.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: Under argon, 785 mg (6.43 mmol) of 4-hydroxybenzaldehyde and 759 mg (8.04 mmol) of (S)-(+)-2-chloro-1-propanol were initially charged in 15.7 ml of DMF. 2.04 g (19.3 mmol) of sodium carbonate were added, and the mixture was then stirred at 130° C. for 20 h. The reaction mixture was purified by preparative HPLC (Chromasil, water/acetonitrile). The reaction mixture was purified by preparative HPLC (Chromasil, water/acetonitrile)