tert-butyl N-[(2R)-2-aminopropyl]carbamate

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

Procedure: (R)-tert-butyl 2-aminopropylcarbamate (338 mg) synthesized according to the method described in PCT publication No. WO2010/006085 was condensed with isoquinoline-6-sulfonyl chloride prepared in Reference Example 1 in the presence of triethylamine (0.538 mL) in dichloromethane to obtain a crude product. Subsequently, 252 mg of the title compound was obtained as a white solid (38%) with reference to the methods of Steps 2 and 3 of Example 1. to obtain a crude product

Conditions: temp:110.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: The product from example 1 step c) (2.0 g) and the product from example 25 step d) (1.3 g) in a solvent of NMP (10 ml) containing Hunigs base (3 ml) was heated at 110° C. for 10 hours. The mixture was evaporated to dryness and purified (SiO2, (1:1) dichloromethane:ethyl acetate as eluant) to give the subtitle compound (1.9 g). The mixture was evaporated to dryness purified (SiO2, (1:1) dichloromethane:ethyl acetate as eluant)

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

Procedure: 72 g (413 mmol) ((R)-2-amino-propyl)-carbamic acid tert-butyl ester were dissolved in MeOH (350 ml) in a jacketed reactor. A solution of 40 ml (438 mmol) methyl acrylate in MeOH (50 ml) was added over 10 min. After 15 h reaction at RT, 108 g (413 mmol) of N-benzyloxycarbonyloxy-succinimide were added in one portion. After 18 h, the reaction mixture was concentrated under reduced pressure affording a yellow oil (ca 270 g). The oil was re-dissolved in 300 mL MeOH and concentrated under reduced pressure (45° C./160-200 mbar) until constant weight to give 219 g of crude titled product as a yellow oil used directly in the next step. After 15 h reaction at RT the reaction mixture was concentrated under reduced pressure

Conditions: temp:110.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: The product from example 1 step c) (2.0 g) and the product from example 25 step d) (1.3 g) in a solvent of NMP (10 ml) containing Hunigs base (3 ml) was heated at 110° C. for 10 hours. The mixture was evaporated to dryness and purified (SiO2, (1:1) dichloromethane:ethyl acetate as eluant) to give the subtitle compound (1.9 g). The mixture was evaporated to dryness purified (SiO2, (1:1) dichloromethane:ethyl acetate as eluant)

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

Procedure: (R)-tert-butyl 2-aminopropylcarbamate (338 mg) synthesized according to the method described in PCT publication No. WO2010/006085 was condensed with isoquinoline-6-sulfonyl chloride prepared in Reference Example 1 in the presence of triethylamine (0.538 mL) in dichloromethane to obtain a crude product. Subsequently, 252 mg of the title compound was obtained as a white solid (38%) with reference to the methods of Steps 2 and 3 of Example 1. to obtain a crude product

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

Procedure: The titled compound (83 mg) was prepared by the method of Example 6, step (f) using the product from Example 6, step (e) (75 mg) and the product from example 9, step (d) (72 mg).

Conditions: temp:110.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: The product from example 1 step c) (2.0 g) and the product from example 25 step d) (1.3 g) in a solvent of NMP (10 ml) containing Hunigs base (3 ml) was heated at 110° C. for 10 hours. The mixture was evaporated to dryness and purified (SiO2, (1:1) dichloromethane:ethyl acetate as eluant) to give the subtitle compound (1.9 g). The mixture was evaporated to dryness purified (SiO2, (1:1) dichloromethane:ethyl acetate as eluant)

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

Procedure: 72 g (413 mmol) ((R)-2-amino-propyl)-carbamic acid tert-butyl ester were dissolved in MeOH (350 ml) in a jacketed reactor. A solution of 40 ml (438 mmol) methyl acrylate in MeOH (50 ml) was added over 10 min. After 15 h reaction at RT, 108 g (413 mmol) of N-benzyloxycarbonyloxy-succinimide were added in one portion. After 18 h, the reaction mixture was concentrated under reduced pressure affording a yellow oil (ca 270 g). The oil was re-dissolved in 300 mL MeOH and concentrated under reduced pressure (45° C./160-200 mbar) until constant weight to give 219 g of crude titled product as a yellow oil used directly in the next step. After 15 h reaction at RT the reaction mixture was concentrated under reduced pressure

Conditions: temp:110.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: The product from example 1 step c) (2.0 g) and the product from example 25 step d) (1.3 g) in a solvent of NMP (10 ml) containing Hunigs base (3 ml) was heated at 110° C. for 10 hours. The mixture was evaporated to dryness and purified (SiO2, (1:1) dichloromethane:ethyl acetate as eluant) to give the subtitle compound (1.9 g). The mixture was evaporated to dryness purified (SiO2, (1:1) dichloromethane:ethyl acetate as eluant)

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

Procedure: (R)-tert-butyl 2-aminopropylcarbamate (338 mg) synthesized according to the method described in PCT publication No. WO2010/006085 was condensed with isoquinoline-6-sulfonyl chloride prepared in Reference Example 1 in the presence of triethylamine (0.538 mL) in dichloromethane to obtain a crude product. Subsequently, 252 mg of the title compound was obtained as a white solid (38%) with reference to the methods of Steps 2 and 3 of Example 1. to obtain a crude product