1-(aminomethyl)cyclobutan-1-ol

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)cyclobutanol (prepared from cyclobutanone as described in WO 2006/100208) (7.2 g, 71 mmol), 3,3-dimethylbutanal (9.8 mL, 78 mmol), 4 Å molecular sieves (10 g, 8-12 mesh beads), potassium thiocyanate (9.2 g, 95 mmol) and iodine (18 g, 71 mmol) in acetonitrile (100 mL) were processed as described in Example 1A to provide the title compound (5.5 g, 23 mmol, 32% yield). MS (DCI/NH3) m/z 241 (M+H)+.

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

Procedure: A mixture of 1-(aminomethyl)cyclobutanol (prepared from cyclobutanone as described in WO 2006/100208) (7.2 g, 71 mmol), 3,3-dimethylbutanal (9.8 mL, 78 mmol), 4 Å molecular sieves (10 g, 8-12 mesh beads), potassium thiocyanate (9.2 g, 95 mmol) and iodine (18 g, 71 mmol) in acetonitrile (100 mL) were processed as described in Example 18A to provide the title compound (5.5 g, 23 mmol, 32% yield). MS (DCI/NH3) m/z 241 (M+H)+.

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

Procedure: A mixture of 1-(aminomethyl)cyclobutanol (prepared from cyclobutanone as described in WO 2006/100208) (7.2 g, 71 mmol), 3,3-dimethylbutanal (9.8 mL, 78 mmol), 4 Å molecular sieves (10 g, 8-12 mesh beads), potassium thiocyanate (9.2 g, 95 mmol) and iodine (18 g, 71 mmol) in acetonitrile (100 mL) were processed as described in Example 18A to provide the title compound (5.5 g, 23 mmol, 32% yield). MS (DCI/NH3) m/z 241 (M+H)+.

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

Procedure: To a solution of 1-(aminomethyl)cyclobutanol (62.5 mmol) in dichloromethane (312 mL) was added triethylamine (8.71 mL, 62.5 mmol) and 4-chloro-3-nitroquinoline (13.04 g, 62.5 mmol). More triethylamine (3 mL) was added almost immediately. The reaction was stirred under N2 for 10 days at room temperature, then was diluted with dichloromethane and washed with 1 M aqueous NaOH. A solid formed and was isolated by filtration. The organic layer was washed with water and brine, dried over Na2SO4, filtered, and concentrated under reduced pressure to yield a solid that was crystallized from 2-propanol. The resulting crystals were combined with the solid that was isolated from the extraction and the mixture was triturated with hot 2-propanol. The solid was isolated by filtration, washed with diethyl ether, and air dried to yield 12.83 g of 1-{[(3-nitroquinolin-4-yl)amino]methyl}cyclobutanol as yellow crystals. washed with 1 M aqueous NaOH A solid formed was isolated by filtration The organic layer was washed with water and brine dried over Na2SO4 filtered concentrated under reduced pressure to yield a solid that was crystallized from 2-propanol that was isolated from the extraction the mixture was triturated with hot 2-propanol The solid was isolated by filtration washed with diethyl ether, and air dried

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

Procedure: A mixture of 1-(aminomethyl)cyclobutanol (prepared from cyclobutanone as described in WO 2006/100208) (7.2 g, 71 mmol), 3,3-dimethylbutanal (9.8 mL, 78 mmol), 4 Å molecular sieves (10 g, 8-12 mesh beads), potassium thiocyanate (9.2 g, 95 mmol) and iodine (18 g, 71 mmol) in acetonitrile (100 mL) were processed as described in Example 18A to provide the title compound (5.5 g, 23 mmol, 32% yield). MS (DCI/NH3) m/z 241 (M+H)+.

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

Procedure: A mixture of 1-(aminomethyl)cyclobutanol (prepared from cyclobutanone as described in WO 2006/100208) (7.2 g, 71 mmol), 3,3-dimethylbutanal (9.8 mL, 78 mmol), 4 Å molecular sieves (10 g, 8-12 mesh beads), potassium thiocyanate (9.2 g, 95 mmol) and iodine (18 g, 71 mmol) in acetonitrile (100 mL) were processed as described in Example 18A to provide the title compound (5.5 g, 23 mmol, 32% yield). MS (DCI/NH3) m/z 241 (M+H)+.

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

Procedure: A mixture of 1-(aminomethyl)cyclobutanol (prepared from cyclobutanone as described in WO 2006/100208) (7.2 g, 71 mmol), 3,3-dimethylbutanal (9.8 mL, 78 mmol), 4 Å molecular sieves (10 g, 8-12 mesh beads), potassium thiocyanate (9.2 g, 95 mmol) and iodine (18 g, 71 mmol) in acetonitrile (100 mL) were processed as described in Example 1A to provide the title compound (5.5 g, 23 mmol, 32% yield). MS (DCI/NH3) m/z 241 (M+H)+.

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

Procedure: A mixture of 1-(aminomethyl)cyclobutanol (prepared from cyclobutanone as described in WO 2006/100208) (7.2 g, 71 mmol), 3,3-dimethylbutanal (9.8 mL, 78 mmol), 4 Å molecular sieves (10 g, 8-12 mesh beads), potassium thiocyanate (9.2 g, 95 mmol) and iodine (18 g, 71 mmol) in acetonitrile (100 mL) were processed as described in Example 1A to provide the title compound (5.5 g, 23 mmol, 32% yield). MS (DCI/NH3) m/z 241 (M+H)+.

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

Procedure: A mixture of 1-(aminomethyl)cyclobutanol (prepared from cyclobutanone as described in WO 2006/100208) (7.2 g, 71 mmol), 3,3-dimethylbutanal (9.8 mL, 78 mmol), 4 Å molecular sieves (10 g, 8-12 mesh beads), potassium thiocyanate (9.2 g, 95 mmol) and iodine (18 g, 71 mmol) in acetonitrile (100 mL) were processed as described in Example 18A to provide the title compound (5.5 g, 23 mmol, 32% yield). MS (DCI/NH3) m/z 241 (M+H)+.

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

Procedure: A solution of 4-chloro-3-nitroquinoline (30.0 g, 144 mmol) in dichloromethane (350 mL) was cooled to 0° C. under a nitrogen atmosphere, and triethylamine (22.1 mL, 158 mmol) was added. A solution of 1-(aminomethyl)cyclobutanol (16.0 g, 158 mmol) in dichloromethane (130 mL) was then added over a period of one hour, followed by a rinse of dichloromethane (100 mL). The reaction was stirred at room temperature overnight. The solvent was removed under reduced pressure, and the residue was triturated in water (500 mL) and saturated aqueous sodium bicarbonate (200 mL) for two hours. A solid was present and was isolated by filtration, washed with a large amount of water, and dried in a vacuum oven at 55° C. to provide 38.7 g of 1-{[(3-nitroquinolin-4-yl)amino]methyl}cyclobutanol as a yellow solid. a rinse of dichloromethane (100 mL) The solvent was removed under reduced pressure the residue was triturated in water (500 mL) saturated aqueous sodium bicarbonate (200 mL) for two hours was isolated by filtration washed with a large amount of water dried in a vacuum oven at 55° C.

Conditions: temp:90.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 1-[(4-Amino-2-methyl-1H-imidazo[4,5-c]quinolin-1-yl)methyl]cyclobutanol was prepared according to the general methods of Example 57 using 4-chloro-3-nitroquinoline in lieu of 4-chloro-3-nitronaphthyridine and 1-(aminomethyl)cyclobutanol in lieu of 1-(aminomethyl)cyclohexanol in Part A and trimethylorthoacetate in lieu of trimethylorthobutyrate in Part C. The crude product was triturated sequentially with ethyl acetate, hot chloroform, and acetonitrile, purified by HPFC eluting with a gradient of 0-40% CMA in chloroform, and then suspended in water (100 mL). Concentrated hydrochloric acid (2 mL) was added and the mixture was heated to 90° C. The hot solution was made basic (pH 10) with solid sodium bicarbonate. The solution was allowed to cool to ambient temperature. A precipitate was isolated by filtration, washed well with water, and then dried to provide pure product as a white powder, mp>250.0° C. Anal. Calcd for C16H18N4O C, 68.06; H, 6.43; N, 19.84. Found: C, 67.99; H, 6.54; N, 19.81. The crude product was triturated sequentially with ethyl acetate, hot chloroform, and acetonitrile purified by HPFC eluting with a gradient of 0-40% CMA in chloroform Concentrated hydrochloric acid (2 mL) was added to cool to ambient temperature A precipitate was isolated by filtration washed well with water dried to provide pure product as a white powder, mp>250.0° C