叔-正丁基-(3-羟基哌啶-4-基)氨基甲酸酯

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

实验步骤: To a solution of [1,2,3]thiadiazolo[5,4-b]pyridin-6-ylmethanol (for a synthesis see WO2003064431, Example 1(b(iv)) (28 mg, 0.166 mmol) in THF (1 ml) was added triethylamine (0.023 ml, 0.166 mmol) and then methanesulfonyl chloride (0.013 ml, 0.166 mmol) and the reaction was then stirred at room temperature for 2 h. DMF (1 ml) was then added followed by (4R)-4-[(4-amino-1-piperidinyl)methyl]-3-fluoro-4,5-dihydro-7H-pyrrolo[3,2,1-de]-1,5-naphthyridin-7-one Enantiomer 1 (50 mg, 0.166 mmol) and potassium carbonate (0.166 mmol) and the reaction was stirred at room temperature for a further 72 h before evaporation. The residue was subjected to column chromatography on silica gel using a dichloromethane, methanol gradient to provide the free base of the title compound (20 mg, 27%).

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

实验步骤: A mixture of 4-{[(3R,4S)-4-amino-3-hydroxy-1-piperidinyl]methyl}-3-fluoro-4,5-dihydro-7H-pyrrolo[3,2,1-de]-1,5-naphthyridin-7-one Diastereomer 1 (54 mg), 3,4-dihydro-2H-pyrano[2,3-c]pyridine-6-carbaldehyde (for a synthesis see WO2004058144, Example 126(c)) (20.6 mg) and 3A molecular sieves in chloroform (1 ml) and methanol (1 ml) was heated at 65° C. for 5 h, cooled and then sodium triacetoxyborohydride (53 mg) was added. The general procedure of Example 72 was then followed to obtain the free base of the title compound (41 mg, 70%). cooled

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

实验步骤: (4R)-4-[(4-amino-1-piperidinyl)methyl]-3-fluoro-4,5-dihydro-7H-pyrrolo[3,2,1-de]-1,5-naphthyridin-7-one Enantiomer 1 (50 mg, 0.166 mmol) and 2-oxo-2,3-dihydro-1H-pyrido[2,3-b][1,4]thiazine-7-carboxaldehyde (for a synthesis see WO2004058144 Example 48(e)) (32 mg, 0.166 mol) were stirred in chloroform (1 mL) and methanol (1 mL) for 2 h at room temperature. Sodium cyanoborohydride (40 g) was added and the mixture was stirred for 18 h. The mixture was filtered and evaporated. Chromatography on silica, eluting with 0-20% methanol/dichloromethane, gave the free base of the title compound (31 mg, 39%). The mixture was filtered evaporated Chromatography on silica, eluting with 0-20% methanol/dichloromethane

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

实验步骤: To a solution of [1,2,3]thiadiazolo[5,4-b]pyridin-6-ylmethanol (for a synthesis see WO2003064431, Example 1(b(iv)) (28 mg, 0.166 mmol) in THF (1 ml) was added triethylamine (0.023 ml, 0.166 mmol) and then methanesulfonyl chloride (0.013 ml, 0.166 mmol) and the reaction was then stirred at room temperature for 2 h. DMF (1 ml) was then added followed by (4R)-4-[(4-amino-1-piperidinyl)methyl]-3-fluoro-4,5-dihydro-7H-pyrrolo[3,2,1-de]-1,5-naphthyridin-7-one Enantiomer 1 (50 mg, 0.166 mmol) and potassium carbonate (0.166 mmol) and the reaction was stirred at room temperature for a further 72 h before evaporation. The residue was subjected to column chromatography on silica gel using a dichloromethane, methanol gradient to provide the free base of the title compound (20 mg, 27%).

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

实验步骤: A mixture of 4-{[(3R,4S)-4-amino-3-hydroxy-1-piperidinyl]methyl}-3-fluoro-4,5-dihydro-7H-pyrrolo[3,2,1-de]-1,5-naphthyridin-7-one Diastereomer 1 (54 mg), 3,4-dihydro-2H-pyrano[2,3-c]pyridine-6-carbaldehyde (for a synthesis see WO2004058144, Example 126(c)) (20.6 mg) and 3A molecular sieves in chloroform (1 ml) and methanol (1 ml) was heated at 65° C. for 5 h, cooled and then sodium triacetoxyborohydride (53 mg) was added. The general procedure of Example 72 was then followed to obtain the free base of the title compound (41 mg, 70%). cooled

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

实验步骤: (4R)-4-[(4-amino-1-piperidinyl)methyl]-3-fluoro-4,5-dihydro-7H-pyrrolo[3,2,1-de]-1,5-naphthyridin-7-one Enantiomer 1 (50 mg, 0.166 mmol) and 2-oxo-2,3-dihydro-1H-pyrido[2,3-b][1,4]thiazine-7-carboxaldehyde (for a synthesis see WO2004058144 Example 48(e)) (32 mg, 0.166 mol) were stirred in chloroform (1 mL) and methanol (1 mL) for 2 h at room temperature. Sodium cyanoborohydride (40 g) was added and the mixture was stirred for 18 h. The mixture was filtered and evaporated. Chromatography on silica, eluting with 0-20% methanol/dichloromethane, gave the free base of the title compound (31 mg, 39%). The mixture was filtered evaporated Chromatography on silica, eluting with 0-20% methanol/dichloromethane

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

实验步骤: To a solution of [1,2,3]thiadiazolo[5,4-b]pyridin-6-ylmethanol (for a synthesis see WO2003064431, Example 1(b(iv)) (28 mg, 0.166 mmol) in THF (1 ml) was added triethylamine (0.023 ml, 0.166 mmol) and then methanesulfonyl chloride (0.013 ml, 0.166 mmol) and the reaction was then stirred at room temperature for 2 h. DMF (1 ml) was then added followed by (4R)-4-[(4-amino-1-piperidinyl)methyl]-3-fluoro-4,5-dihydro-7H-pyrrolo[3,2,1-de]-1,5-naphthyridin-7-one Enantiomer 1 (50 mg, 0.166 mmol) and potassium carbonate (0.166 mmol) and the reaction was stirred at room temperature for a further 72 h before evaporation. The residue was subjected to column chromatography on silica gel using a dichloromethane, methanol gradient to provide the free base of the title compound (20 mg, 27%).

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

实验步骤: A mixture of 4-{[(3R,4S)-4-amino-3-hydroxy-1-piperidinyl]methyl}-3-fluoro-4,5-dihydro-7H-pyrrolo[3,2,1-de]-1,5-naphthyridin-7-one Diastereomer 1 (54 mg), 3,4-dihydro-2H-pyrano[2,3-c]pyridine-6-carbaldehyde (for a synthesis see WO2004058144, Example 126(c)) (20.6 mg) and 3A molecular sieves in chloroform (1 ml) and methanol (1 ml) was heated at 65° C. for 5 h, cooled and then sodium triacetoxyborohydride (53 mg) was added. The general procedure of Example 72 was then followed to obtain the free base of the title compound (41 mg, 70%). cooled

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

实验步骤: (4R)-4-[(4-amino-1-piperidinyl)methyl]-3-fluoro-4,5-dihydro-7H-pyrrolo[3,2,1-de]-1,5-naphthyridin-7-one Enantiomer 1 (50 mg, 0.166 mmol) and 2-oxo-2,3-dihydro-1H-pyrido[2,3-b][1,4]thiazine-7-carboxaldehyde (for a synthesis see WO2004058144 Example 48(e)) (32 mg, 0.166 mol) were stirred in chloroform (1 mL) and methanol (1 mL) for 2 h at room temperature. Sodium cyanoborohydride (40 g) was added and the mixture was stirred for 18 h. The mixture was filtered and evaporated. Chromatography on silica, eluting with 0-20% methanol/dichloromethane, gave the free base of the title compound (31 mg, 39%). The mixture was filtered evaporated Chromatography on silica, eluting with 0-20% methanol/dichloromethane