4-HYDROXYAZEPANE-1-CARBOXYLIC ACID TERT-BUTYL ESTER

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

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

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: A solution of tert-butyl 4-oxoazepane-1-carboxylate (0.60 g, 2.81 mmol), in MeOH (11 mL) was cooled to 0° C. NaBH4 (0.266 g, 7.03 mmol) was added and the mixture was slowly warmed to ambient temperature where the reaction stirred overnight. The mixture was concentrated in vacuo and the residue was taken up in EtOAc (20 mL) and saturated aqueous NH4Cl solution (20 mL) The layers were separated and the aqueous phase was extracted with EtOAc (2×10 mL) The combined organic extracts were washed with brine and dried over Na2SO4, then filtered and concentrated. The product was isolated as a thick colorless oil that solidified overnight to a white solid. The mixture was concentrated in vacuo saturated aqueous NH4Cl solution (20 mL) The layers were separated the aqueous phase was extracted with EtOAc (2×10 mL) The combined organic extracts were washed with brine dried over Na2SO4 filtered concentrated The product was isolated as a thick colorless oil that solidified overnight to a white solid

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

Procedure: A solution of tert-butyl 4-oxoazepane-1-carboxylate (0.60 g, 2.81 mmol), in MeOH (11 mL) was cooled to 0° C. NaBH4 (0.266 g, 7.03 mmol) was added and the mixture was slowly warmed to ambient temperature where the reaction stirred overnight. The mixture was concentrated in vacuo and the residue was taken up in EtOAc (20 mL) and saturated aqueous NH4Cl solution (20 mL) The layers were separated and the aqueous phase was extracted with EtOAc (2×10 mL) The combined organic extracts were washed with brine and dried over Na2SO4, then filtered and concentrated. The product was isolated as a thick colorless oil that solidified overnight to a white solid. The mixture was concentrated in vacuo saturated aqueous NH4Cl solution (20 mL) The layers were separated the aqueous phase was extracted with EtOAc (2×10 mL) The combined organic extracts were washed with brine dried over Na2SO4 filtered concentrated The product was isolated as a thick colorless oil that solidified overnight to a white solid

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

Procedure: Following the procedure described in Example 1, and substituting Compound 1B2 in Step (1) with tert-butyl 4-hydroxyazepane-1-carboxylate (2B2) (200 mg, 0.93 mmol) and Compound 1E in Step 4 with 2-(2,6-difluorophenyl)thiazole-4-carboxylic acid (2E) (40 mg, 0.166 mmol), the title compound 2 (35 mg, 0.080 mmol) was obtained.

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

Procedure: Following the procedure described in Example 1, and substituting Compound 1B2 in Step (1) with tert-butyl 4-hydroxyazepane-1-carboxylate (2B2) (200 mg, 0.93 mmol) and Compound 1E in Step 4 with 2-(2,6-difluorophenyl)thiazole-4-carboxylic acid (2E) (40 mg, 0.166 mmol), the title compound 2 (35 mg, 0.080 mmol) was obtained.

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

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

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

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