2-[(2S)-pyrrolidin-2-yl]propan-2-ol

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

Procedure: The title compound was prepared from 7-(2-methyl-1H-indol-5-ylamino)-thieno[3,2-b]pyridine-2-carboxylic acid and (S)-2-pyrrolidin-2-yl-propan-2-ol by a procedure analogous to Example 21B. MS: 435.3; HPLC Rf: 4.134 min.; HPLC purity 95%.

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

Procedure: A mixture of (S)-2-(1-hydroxy-1-methyl-ethyl)-pyrrolidine-1-carboxylic acid benzyl ester (0.727 g, 2.76 mmol) and Pd/C (10%, 72 mg) in EtOH was shaken with H2 in a Parr bottle under 50 psi. After 12 h the reaction mixture was filtered through celite. HCl (9 mmol, 1 N in Et2O) was added to the filtrate, the filtrate was then concentrated to give a white solid (350 mg, 98%). After 12 h the reaction mixture was filtered through celite the filtrate was then concentrated

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

Procedure: A mixture of (S)-2-(1-hydroxy-1-methyl-ethyl)-pyrrolidine-1-carboxylic acid benzyl ester (0.727 g, 2.76 mmol) and Pd/C (10%, 72 mg) in EtOH was shaken with H2 in a Parr bottle under 50 psi. After 12 h the reaction mixture was filtered through celite. HCl (9 mmol, 1 N in Et2O) was added to the filtrate, the filtrate was then concentrated to give a white solid (350 mg, 98%). After 12 h the reaction mixture was filtered through celite the filtrate was then concentrated

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

Procedure: To a solution of (S)-2-(1-benzylpyrrolidin-2-yl)propan-2-ol (1.38 g, 6.29 mmol) in MeOH (50 mL) was added palladium hydroxide, 20 wt % pd (dry basis) on carbon, wet, degussa type e101 ne/w (230 mg, 1.64 mmol) and acetic acid glacial (690 μl, 12.0 mmol). The reaction mixture was stirred at RT under 1 atm of H2 for 24 h. The reaction mixture was filtered through a pad of celite and washed with MeOH. The solvent was evaporated and the residue was partitioned between 2 N NaOH and EtOAc. The aqueous layer was extracted with EtOAc (2×) and the combined organic layer was dried (Na2SO4) and concentrated. The crude product was chromatographed through a Redi-Sep® pre-packed silica gel column (40 g), eluting with a gradient of 50% to 100% MeOH in EtOAc, to provide (S)-2-(pyrrolidin-2-yl)propan-2-ol as an orange oil. palladium hydroxide, 20 wt % pd (dry basis) on carbon The reaction mixture was filtered through a pad of celite washed with MeOH The solvent was evaporated the residue was partitioned between 2 N NaOH and EtOAc The aqueous layer was extracted with EtOAc (2×) the combined organic layer was dried (Na2SO4) concentrated The crude product was chromatographed through a Redi-Sep® pre-packed silica gel column (40 g) eluting with a gradient of 50% to 100% MeOH in EtOAc

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

Procedure: To a solution of (S)-2-(1-benzylpyrrolidin-2-yl)propan-2-ol (1.38 g, 6.29 mmol) in MeOH (50 mL) was added palladium hydroxide, 20 wt % pd (dry basis) on carbon, wet, degussa type e101 ne/w (230 mg, 1.64 mmol) and acetic acid glacial (690 μl, 12.0 mmol). The reaction mixture was stirred at RT under 1 atm of H2 for 24 h. The reaction mixture was filtered through a pad of celite and washed with MeOH. The solvent was evaporated and the residue was partitioned between 2 N NaOH and EtOAc. The aqueous layer was extracted with EtOAc (2×) and the combined organic layer was dried (Na2SO4) and concentrated. The crude product was chromatographed through a Redi-Sep® pre-packed silica gel column (40 g), eluting with a gradient of 50% to 100% MeOH in EtOAc, to provide (S)-2-(pyrrolidin-2-yl)propan-2-ol as an orange oil. palladium hydroxide, 20 wt % pd (dry basis) on carbon The reaction mixture was filtered through a pad of celite washed with MeOH The solvent was evaporated the residue was partitioned between 2 N NaOH and EtOAc The aqueous layer was extracted with EtOAc (2×) the combined organic layer was dried (Na2SO4) concentrated The crude product was chromatographed through a Redi-Sep® pre-packed silica gel column (40 g) eluting with a gradient of 50% to 100% MeOH in EtOAc

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

Procedure: To a solution of (S)-2-(1-benzylpyrrolidin-2-yl)propan-2-ol (1.38 g, 6.29 mmol) in MeOH (50 mL) was added palladium hydroxide, 20 wt % pd (dry basis) on carbon, wet, degussa type e101 ne/w (230 mg, 1.64 mmol) and acetic acid glacial (690 μl, 12.0 mmol). The reaction mixture was stirred at RT under 1 atm of H2 for 24 h. The reaction mixture was filtered through a pad of celite and washed with MeOH. The solvent was evaporated and the residue was partitioned between 2 N NaOH and EtOAc. The aqueous layer was extracted with EtOAc (2×) and the combined organic layer was dried (Na2SO4) and concentrated. The crude product was chromatographed through a Redi-Sep® pre-packed silica gel column (40 g), eluting with a gradient of 50% to 100% MeOH in EtOAc, to provide (S)-2-(pyrrolidin-2-yl)propan-2-ol as an orange oil. palladium hydroxide, 20 wt % pd (dry basis) on carbon The reaction mixture was filtered through a pad of celite washed with MeOH The solvent was evaporated the residue was partitioned between 2 N NaOH and EtOAc The aqueous layer was extracted with EtOAc (2×) the combined organic layer was dried (Na2SO4) concentrated The crude product was chromatographed through a Redi-Sep® pre-packed silica gel column (40 g) eluting with a gradient of 50% to 100% MeOH in EtOAc

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

Procedure: To a solution of (S)-2-(1-benzylpyrrolidin-2-yl)propan-2-ol (1.38 g, 6.29 mmol) in MeOH (50 mL) was added palladium hydroxide, 20 wt % pd (dry basis) on carbon, wet, degussa type e101 ne/w (230 mg, 1.64 mmol) and acetic acid glacial (690 μl, 12.0 mmol). The reaction mixture was stirred at RT under 1 atm of H2 for 24 h. The reaction mixture was filtered through a pad of celite and washed with MeOH. The solvent was evaporated and the residue was partitioned between 2 N NaOH and EtOAc. The aqueous layer was extracted with EtOAc (2×) and the combined organic layer was dried (Na2SO4) and concentrated. The crude product was chromatographed through a Redi-Sep® pre-packed silica gel column (40 g), eluting with a gradient of 50% to 100% MeOH in EtOAc, to provide (S)-2-(pyrrolidin-2-yl)propan-2-ol as an orange oil. palladium hydroxide, 20 wt % pd (dry basis) on carbon The reaction mixture was filtered through a pad of celite washed with MeOH The solvent was evaporated the residue was partitioned between 2 N NaOH and EtOAc The aqueous layer was extracted with EtOAc (2×) the combined organic layer was dried (Na2SO4) concentrated The crude product was chromatographed through a Redi-Sep® pre-packed silica gel column (40 g) eluting with a gradient of 50% to 100% MeOH in EtOAc

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

Procedure: To a solution of (S)-2-(1-benzylpyrrolidin-2-yl)propan-2-ol (1.38 g, 6.29 mmol) in MeOH (50 mL) was added palladium hydroxide, 20 wt % pd (dry basis) on carbon, wet, degussa type e101 ne/w (230 mg, 1.64 mmol) and acetic acid glacial (690 μl, 12.0 mmol). The reaction mixture was stirred at RT under 1 atm of H2 for 24 h. The reaction mixture was filtered through a pad of celite and washed with MeOH. The solvent was evaporated and the residue was partitioned between 2 N NaOH and EtOAc. The aqueous layer was extracted with EtOAc (2×) and the combined organic layer was dried (Na2SO4) and concentrated. The crude product was chromatographed through a Redi-Sep® pre-packed silica gel column (40 g), eluting with a gradient of 50% to 100% MeOH in EtOAc, to provide (S)-2-(pyrrolidin-2-yl)propan-2-ol as an orange oil. palladium hydroxide, 20 wt % pd (dry basis) on carbon The reaction mixture was filtered through a pad of celite washed with MeOH The solvent was evaporated the residue was partitioned between 2 N NaOH and EtOAc The aqueous layer was extracted with EtOAc (2×) the combined organic layer was dried (Na2SO4) concentrated The crude product was chromatographed through a Redi-Sep® pre-packed silica gel column (40 g) eluting with a gradient of 50% to 100% MeOH in EtOAc

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

Procedure: The title compound was prepared from 7-(2-methyl-1H-indol-5-ylamino)-thieno[3,2-b]pyridine-2-carboxylic acid and (S)-2-pyrrolidin-2-yl-propan-2-ol by a procedure analogous to Example 21B. MS: 435.3; HPLC Rf: 4.134 min.; HPLC purity 95%.

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

Procedure: A mixture of (S)-2-(1-hydroxy-1-methyl-ethyl)-pyrrolidine-1-carboxylic acid benzyl ester (0.727 g, 2.76 mmol) and Pd/C (10%, 72 mg) in EtOH was shaken with H2 in a Parr bottle under 50 psi. After 12 h the reaction mixture was filtered through celite. HCl (9 mmol, 1 N in Et2O) was added to the filtrate, the filtrate was then concentrated to give a white solid (350 mg, 98%). After 12 h the reaction mixture was filtered through celite the filtrate was then concentrated

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

Procedure: To a solution of (S)-2-(1-benzylpyrrolidin-2-yl)propan-2-ol (1.38 g, 6.29 mmol) in MeOH (50 mL) was added palladium hydroxide, 20 wt % pd (dry basis) on carbon, wet, degussa type e101 ne/w (230 mg, 1.64 mmol) and acetic acid glacial (690 μl, 12.0 mmol). The reaction mixture was stirred at RT under 1 atm of H2 for 24 h. The reaction mixture was filtered through a pad of celite and washed with MeOH. The solvent was evaporated and the residue was partitioned between 2 N NaOH and EtOAc. The aqueous layer was extracted with EtOAc (2×) and the combined organic layer was dried (Na2SO4) and concentrated. The crude product was chromatographed through a Redi-Sep® pre-packed silica gel column (40 g), eluting with a gradient of 50% to 100% MeOH in EtOAc, to provide (S)-2-(pyrrolidin-2-yl)propan-2-ol as an orange oil. palladium hydroxide, 20 wt % pd (dry basis) on carbon The reaction mixture was filtered through a pad of celite washed with MeOH The solvent was evaporated the residue was partitioned between 2 N NaOH and EtOAc The aqueous layer was extracted with EtOAc (2×) the combined organic layer was dried (Na2SO4) concentrated The crude product was chromatographed through a Redi-Sep® pre-packed silica gel column (40 g) eluting with a gradient of 50% to 100% MeOH in EtOAc