1-(3-aminopropyl)piperidin-4-ol

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: Ethanol (200 ml) and palladium carbon (2.5 g) were added to benzyl N-(3-(4-hydroxypiperidino)propyl)carbamate (2.96 g); and the reaction mixture was stirred vigorously under hydrogen atmosphere overnight. Palladium carbon was removed by filtration, and the filtrate was concentrated to yield the title compound (1.5 g). Palladium carbon was removed by filtration the filtrate was concentrated

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

Procedure: Ethanol (200 ml) and palladium carbon (2.5 g) were added to benzyl N-(3-(4-hydroxypiperidino)propyl)carbamate (2.96 g); and the reaction mixture was stirred vigorously under hydrogen atmosphere overnight. Palladium carbon was removed by filtration, and the filtrate was concentrated to yield the title compound (1.5 g). Palladium carbon was removed by filtration the filtrate was concentrated

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

Procedure: Ethanol (200 ml) and palladium carbon (2.5 g) were added to benzyl N-(3-(4-hydroxypiperidino)propyl)carbamate (2.96 g); and the reaction mixture was stirred vigorously under hydrogen atmosphere overnight. Palladium carbon was removed by filtration, and the filtrate was concentrated to yield the title compound (1.5 g). Palladium carbon was removed by filtration the filtrate was concentrated

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

Procedure: Ethanol (200 ml) and palladium carbon (2.5 g) were added to benzyl N-(3-(4-hydroxypiperidino)propyl)carbamate (2.96 g); and the reaction mixture was stirred vigorously under hydrogen atmosphere overnight. Palladium carbon was removed by filtration, and the filtrate was concentrated to yield the title compound (1.5 g). Palladium carbon was removed by filtration the filtrate was concentrated

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

Procedure: Ethanol (200 ml) and palladium carbon (2.5 g) were added to benzyl N-(3-(4-hydroxypiperidino)propyl)carbamate (2.96 g); and the reaction mixture was stirred vigorously under hydrogen atmosphere overnight. Palladium carbon was removed by filtration, and the filtrate was concentrated to yield the title compound (1.5 g). Palladium carbon was removed by filtration the filtrate was concentrated

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

Procedure: A mixture of 0.045 g (0.1 mmole) of 4-(9-cyclopentyl-7,7-difluoro-5-methyl-6-oxo-6,7,8,9-tetrahydro-5H-pyrimido[4,5-b][1,4]diazepin-2-ylamino)-3-methoxybenzoic acid (I-22), 0.042 g (0.110 mmole) of 1-[bis(dimethylamino)methylene]-1H-1,2,3-triazolo[4,5-b]pyridinium-3-oxide hexafluorophosphate, 0.052 ml (0.300 mmole) of ethyldiisopropyl amine and 1.0 mL of dimethylformamide was stirred for 5 minutes and then 0.019 g (0.12 mmole) 1-(3-Amino-propyl)-piperidin-4-ol was added. The mixture was stirred for 3 hours, then diluted with 10 mL of water plus 2 mL of saturated aqueous sodium bicarbonate and then extracted 3 times with 10 mL of ethyl acetate. The combined extracts were washed with brine, dried over anhydrous magnesium sulfate, filtered and concentrated under reduced pressure. The residue was purified by reverse phase silica gel chromatography, eluting with water-acetonitrile (gradient, 0:100-80:20) to give 0.049 g of 4-(9-cyclopentyl-7,7-difluoro-5-methyl-6-oxo-6,7,8,9-tetrahydro-5H-pyrimido[4,5-b][1,4]diazepin-2-ylamino)-N-[3-(4-hydroxy-piperidin-1-yl)-propyl]-3-methoxy-benzamide (I-105) as a white solid. The mixture was stirred for 3 hours extracted 3 times with 10 mL of ethyl acetate The combined extracts were washed with brine dried over anhydrous magnesium sulfate filtered concentrated under reduced pressure The residue was purified by reverse phase silica gel chromatography eluting with water-acetonitrile (gradient, 0:100-80:20)