1-Propanamine, 3-[[(1,1-dimethylethyl)dimethylsilyl]oxy]-

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

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

Procedure: Triethylamine (1.16 ml, 16 mmol), followed by methanesulfonyl chloride (Compound 19, 1.48 ml, 19.2 mmol) was added to a solution of 3-tert-butyldimethylsiloxy-1-propylamine (Compound 29, 2.80 g, 16 mmol) in tetrahydrofuran (60 ml) at 0° C. under argon. After stirring at room temperature overnight, the mixture was washed successively with dilute hydrochloric acid, saturated sodium bicarbonate and brine. Evaporation of the dried (magnesium sulfate) organic phase gave the title sulfonamide. 1HNMR(CDCl3): 0.04 (s, 6H), 0.87 (s, 9H), 1.76 (p, 2H, J=6.4 Hz), 2.91 (s, 3H), 3.24 (q, 2H, J=6.2 Hz), 3.74 (t, 2H, J=5.52 Hz) and 5.05 (br t, 1H). the mixture was washed successively with dilute hydrochloric acid, saturated sodium bicarbonate and brine Evaporation of the dried (magnesium sulfate) organic phase

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

Procedure: tert-Butyldimethylsilyl chloride (14.7 g, 97.5 mmol), followed by 1,8-diazabicyclo[5.4.0]undec-7-ene (14.6 ml, 97.5 mmol) was added to a solution 3-amino-1-propanol (7.45 ml, 97.5 mmol) in dichloromethane (100 ml) at 0° C. under argon. After 6 hours stirring at room temperature, the mixture was quenched with water and washed successively with 10% hydrochloric acid, saturated sodium bicarbonate solution and brine. Evaporation of the dried (magnesium sulfate) organic phase gave the title amine. 1 (HNMR(CDCl3): -0.03 (s, 6H), 0.81 (s, 9H), 1.61 (p, 2H, J=6.1 Hz), 2.20 (br, 2H), 2.75 (t, 2H, J=6.8 Hz) and 3.63 (t, 2H, J=6.12 Hz). the mixture was quenched with water washed successively with 10% hydrochloric acid, saturated sodium bicarbonate solution and brine Evaporation of the dried (magnesium sulfate) organic phase

Conditions: temp:90.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 5-(6-chloro-4-(isopropylamino)pyridin-3-yl)-1,3,4-oxadiazol-2(3H)-one (49) (1.2 g, 4 mmol) and 3-((tert-butyldimethylsilyl)oxy)propan-1-amine (48) (7 mmol, 1.5 equiv.) were dissolved in ethanol (5 mL). Refluxed the reaction mixture at 90° C., overnight. The reaction mass was concentrated under reduced pressure to remove excess of solvent. The crude material obtained was taken to next step as such, without purification. LC/MS: Acquity BEH C18 2.1×50 mm, 1.8 micron; Solvent A=0.1% TFA in water; Solvent B=0.1% TFA in ACN; gradient 0-100% B over 2 min; retention time: 1.02 min; LCMS (ES-API), m/z 444.9 (M+H). overnight The reaction mass was concentrated under reduced pressure to remove excess of solvent

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

Procedure: To a stirred solution of 3-aminopropan-1-ol (2 g, 20 mmol) in DCM (10 mL), imidazole (79 mmol, 3 equiv.) was added and stirred at room temperature for 10 min. Reaction mixture was cooled to 0° C., t-butyl dimethyl silyl chloride (30 mmol, 1.2 equiv.) was added in portions and stirred the reaction mixture overnight at room temperature. Diluted the reaction mixture using DCM, the DCM layer was washed with water. The organic layer was collected, dried over Na2SO4, filtered and concentrated. ELSD method LC/MS: Retention time: 1.5 min; (ES-API), m/z 189.7 (M+H). Reaction mixture was cooled to 0° C. stirred the reaction mixture overnight at room temperature Diluted the reaction mixture the DCM layer was washed with water The organic layer was collected dried over Na2SO4 filtered concentrated

Conditions: temp:90.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 5-(6-chloro-4-(isopropylamino)pyridin-3-yl)-1,3,4-oxadiazol-2(3H)-one (49) (1.2 g, 4 mmol) and 3-((tert-butyldimethylsilyl)oxy)propan-1-amine (48) (7 mmol, 1.5 equiv.) were dissolved in ethanol (5 mL). Refluxed the reaction mixture at 90° C., overnight. The reaction mass was concentrated under reduced pressure to remove excess of solvent. The crude material obtained was taken to next step as such, without purification. LC/MS: Acquity BEH C18 2.1×50 mm, 1.8 micron; Solvent A=0.1% TFA in water; Solvent B=0.1% TFA in ACN; gradient 0-100% B over 2 min; retention time: 1.02 min; LCMS (ES-API), m/z 444.9 (M+H). overnight The reaction mass was concentrated under reduced pressure to remove excess of solvent

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

Procedure: To a stirred solution of 3-aminopropan-1-ol (2 g, 20 mmol) in DCM (10 mL), imidazole (79 mmol, 3 equiv.) was added and stirred at room temperature for 10 min. Reaction mixture was cooled to 0° C., t-butyl dimethyl silyl chloride (30 mmol, 1.2 equiv.) was added in portions and stirred the reaction mixture overnight at room temperature. Diluted the reaction mixture using DCM, the DCM layer was washed with water. The organic layer was collected, dried over Na2SO4, filtered and concentrated. ELSD method LC/MS: Retention time: 1.5 min; (ES-API), m/z 189.7 (M+H). Reaction mixture was cooled to 0° C. stirred the reaction mixture overnight at room temperature Diluted the reaction mixture the DCM layer was washed with water The organic layer was collected dried over Na2SO4 filtered concentrated

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

Procedure: To a stirred solution of 3-aminopropan-1-ol (2 g, 20 mmol) in DCM (10 mL), imidazole (79 mmol, 3 equiv.) was added and stirred at room temperature for 10 min. Reaction mixture was cooled to 0° C., t-butyl dimethyl silyl chloride (30 mmol, 1.2 equiv.) was added in portions and stirred the reaction mixture overnight at room temperature. Diluted the reaction mixture using DCM, the DCM layer was washed with water. The organic layer was collected, dried over Na2SO4, filtered and concentrated. ELSD method LC/MS: Retention time: 1.5 min; (ES-API), m/z 189.7 (M+H). Reaction mixture was cooled to 0° C. stirred the reaction mixture overnight at room temperature Diluted the reaction mixture the DCM layer was washed with water The organic layer was collected dried over Na2SO4 filtered concentrated

Conditions: temp:90.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 5-(6-chloro-4-(isopropylamino)pyridin-3-yl)-1,3,4-oxadiazol-2(3H)-one (49) (1.2 g, 4 mmol) and 3-((tert-butyldimethylsilyl)oxy)propan-1-amine (48) (7 mmol, 1.5 equiv.) were dissolved in ethanol (5 mL). Refluxed the reaction mixture at 90° C., overnight. The reaction mass was concentrated under reduced pressure to remove excess of solvent. The crude material obtained was taken to next step as such, without purification. LC/MS: Acquity BEH C18 2.1×50 mm, 1.8 micron; Solvent A=0.1% TFA in water; Solvent B=0.1% TFA in ACN; gradient 0-100% B over 2 min; retention time: 1.02 min; LCMS (ES-API), m/z 444.9 (M+H). overnight The reaction mass was concentrated under reduced pressure to remove excess of solvent

Conditions: temp:90.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 5-(6-chloro-4-(isopropylamino)pyridin-3-yl)-1,3,4-oxadiazol-2(3H)-one (49) (1.2 g, 4 mmol) and 3-((tert-butyldimethylsilyl)oxy)propan-1-amine (48) (7 mmol, 1.5 equiv.) were dissolved in ethanol (5 mL). Refluxed the reaction mixture at 90° C., overnight. The reaction mass was concentrated under reduced pressure to remove excess of solvent. The crude material obtained was taken to next step as such, without purification. LC/MS: Acquity BEH C18 2.1×50 mm, 1.8 micron; Solvent A=0.1% TFA in water; Solvent B=0.1% TFA in ACN; gradient 0-100% B over 2 min; retention time: 1.02 min; LCMS (ES-API), m/z 444.9 (M+H). overnight The reaction mass was concentrated under reduced pressure to remove excess of solvent

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

Procedure: To a stirred solution of 3-aminopropan-1-ol (2 g, 20 mmol) in DCM (10 mL), imidazole (79 mmol, 3 equiv.) was added and stirred at room temperature for 10 min. Reaction mixture was cooled to 0° C., t-butyl dimethyl silyl chloride (30 mmol, 1.2 equiv.) was added in portions and stirred the reaction mixture overnight at room temperature. Diluted the reaction mixture using DCM, the DCM layer was washed with water. The organic layer was collected, dried over Na2SO4, filtered and concentrated. ELSD method LC/MS: Retention time: 1.5 min; (ES-API), m/z 189.7 (M+H). Reaction mixture was cooled to 0° C. stirred the reaction mixture overnight at room temperature Diluted the reaction mixture the DCM layer was washed with water The organic layer was collected dried over Na2SO4 filtered concentrated