1-(aminomethyl)cyclopropan-1-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:

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

Procedure: A mixture of 1-(aminomethyl)cyclopropanol (ChemPacific, 1.0 g, 11.5 mmol), 3,3-dimethylbutanal (1.6 mL, 12.6 mmol), 4 Å molecular sieves (3 g, 8-12 mesh beads), potassium thiocyanate (1.5 g, 15 mmol) and iodine (2.9 g, 11.5 mmol) in acetonitrile (25 mL) were processed as described in Example 18A to provide the title compound (2.5 g, 11 mmol, 95% yield). MS (DCI/NH3) m/z 227 (M+H)+.

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

Procedure: A mixture of 1-(aminomethyl)cyclopropanol (ChemPacific, 1.0 g, 11.5 mmol), 3,3-dimethylbutanal (1.6 mL, 12.6 mmol), 4 Å molecular sieves (3 g, 8-12 mesh beads), potassium thiocyanate (1.5 g, 15 mmol) and iodine (2.9 g, 11.5 mmol) in acetonitrile (25 mL) were processed as described in Example 18A to provide the title compound (2.5 g, 11 mmol, 95% yield). MS (DCI/NH3) m/z 227 (M+H)+.

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

Procedure: To a 0° C. mixture of 1-(aminomethyl)cyclopropanol (approximately 36.7 mmol, prepared as described by Lysenko, I. L. and Kulinkovich, O. G. Russ. i J. Org Chem. 2001, 17, 1238-1243) and triethylamine (6.30 mL, 45.4 mmol) in dichloromethane (120 mL) was added a solution of 4-chloro-3-nitroquinoline (7.28 g, 34.9 mmol) in dichloromethane (30 mL). The suspension was stirred at room temperature over the weekend. The dichloromethane was removed under reduced pressure and the residue was suspended in water (150 mL) and stirred at room temperature for 3 hours. A solid was isolated by filtration and dried in a vacuum oven to afford 8.99 g of 1-{[(3-nitroquinolin-4-yl)amino]methyl}cyclopropanol as a yellow solid. prepared The dichloromethane was removed under reduced pressure stirred at room temperature for 3 hours A solid was isolated by filtration dried in a vacuum oven

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

Procedure: A mixture of 1-(aminomethyl)cyclopropanol (ChemPacific, 1.0 g, 11.5 mmol), 3,3-dimethylbutanal (1.6 mL, 12.6 mmol), 4 Å molecular sieves (3 g, 8-12 mesh beads), potassium thiocyanate (1.5 g, 15 mmol) and iodine (2.9 g, 11.5 mmol) in acetonitrile (25 mL) were processed as described in Example 18A to provide the title compound (2.5 g, 11 mmol, 95% yield). MS (DCI/NH3) m/z 227 (M+H)+.

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

Procedure: A mixture of 1-(aminomethyl)cyclopropanol (ChemPacific, 1.0 g, 11.5 mmol), 3,3-dimethylbutanal (1.6 mL, 12.6 mmol), 4 Å molecular sieves (3 g, 8-12 mesh beads), potassium thiocyanate (1.5 g, 15 mmol) and iodine (2.9 g, 11.5 mmol) in acetonitrile (25 mL) were processed as described in Example 18A to provide the title compound (2.5 g, 11 mmol, 95% yield). MS (DCI/NH3) m/z 227 (M+H)+.

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

Procedure: 1-(Aminomethyl)cyclopropanol was prepared using the method of I. L. Lysenko and O. G. Kulinkovich, Russ. J. Org. Chem., 37, pp. 1238-1243 (2001). A solution of 4-chloro-3-nitroquinoline (7.28 g, 34.9 mmol) in dichloromethane (30 mL) was added dropwise to a 0° C. stirred suspension of 1-(aminomethyl)cyclopropanol (36.7 mmol) and triethylamine (6.30 mL, 45.4 mmol) in dichloromethane (120 mL). The mixture was stirred at room temperature for 3 days, then was concentrated under reduced pressure. The residue was suspended in water (150 mL) and was stirred for 3 hours. The solid was isolated by filtration, washed with water (50 mL), and dried in a vacuum oven at 75° C. to afford 8.99 g of 1-{[(3-nitroquinolin-4-yl)amino]methyl}cyclopropanol as a yellow solid. The mixture was stirred at room temperature for 3 days was concentrated under reduced pressure was stirred for 3 hours The solid was isolated by filtration washed with water (50 mL) dried in a vacuum oven at 75° C.

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

Procedure: 1-(Aminomethyl)cyclopropanol was prepared using the method of I. L. Lysenko and O. G. Kulinkovich, Russ. J. Org. Chem., 37, pp. 1238-1243 (2001). A solution of 4-chloro-3-nitroquinoline (7.28 g, 34.9 mmol) in dichloromethane (30 mL) was added dropwise to a 0° C. stirred suspension of 1-(aminomethyl)cyclopropanol (36.7 mmol) and triethylamine (6.30 mL, 45.4 mmol) in dichloromethane (120 mL). The mixture was stirred at room temperature for 3 days, then was concentrated under reduced pressure. The residue was suspended in water (150 mL) and was stirred for 3 hours. The solid was isolated by filtration, washed with water (50 mL), and dried in a vacuum oven at 75° C. to afford 8.99 g of 1-{[(3-nitroquinolin-4-yl)amino]methyl}cyclopropanol as a yellow solid. The mixture was stirred at room temperature for 3 days was concentrated under reduced pressure was stirred for 3 hours The solid was isolated by filtration washed with water (50 mL) dried in a vacuum oven at 75° C.

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

Procedure: A mixture of 1-(aminomethyl)cyclopropanol (ChemPacific, 1.0 g, 11.5 mmol), 3,3-dimethylbutanal (1.6 mL, 12.6 mmol), 4 Å molecular sieves (3 g, 8-12 mesh beads), potassium thiocyanate (1.5 g, 15 mmol) and iodine (2.9 g, 11.5 mmol) in acetonitrile (25 mL) were processed as described in Example 18A to provide the title compound (2.5 g, 11 mmol, 95% yield). MS (DCI/NH3) m/z 227 (M+H)+.

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

Procedure: 1-[(4-Amino-2-propyl-1H-imidazo[4,5-c][1,5]naphthyridin-1-yl)methyl]cyclopropanol was prepared according to the general methods of Parts D through G of Example 84 using 1-(aminomethyl)cyclopropanol in lieu of 1-(2-aminoethyl)cyclopropanol in Part D, 4-chloro-3-nitronaphthyridine in lieu of 4-chloro-3-nitroquinoline in Part D, and trimethyl orthobutyrate in lieu of triethyl orthopropionate in Part F. The crude product was triturated with hot acetonitrile to provide a tan solid. Which was recrystallized from chloroform and hexanes and dried at 140° C. under vacuum to provide product as an off-white solid, mp 199-200° C. MS (ESI) m/z 298 (M+H)+; Anal. calcd for C16H19N5O: C, 64.63; H, 6.44; N, 23.55. Found: C, 64.32; H, 6.62; N, 23.67. The crude product was triturated with hot acetonitrile to provide a tan solid Which was recrystallized from chloroform and hexanes dried at 140° C. under vacuum to provide product as an off-white solid, mp 199-200° C