2-chloro-N'-hydroxybenzenecarboximidamide

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

Procedure: 2-Chlorobenzamidoxime (3.4 g), 2-chlorobenzaldehyde (2.8 g), p-toluenesulphonic acid (1 g) and toluene (100 ml) were heated to reflux for 16 hours in Dean and Stark apparatus. The solution was then run down, and the residue was recrystallised from methanol to give 1.4 g of desired product, mp 75°-78° C. to reflux for 16 hours in Dean and Stark apparatus the residue was recrystallised from methanol

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

Procedure: 2-Chlorobenzoyl chloride (2.6 g) was dissolved in dioxan (90 ml) and 2-chlorobenzamidoxime (2.5 g) was added with stirring, followed by boron trifluoride etherate (0.2 ml). The solution was heated at reflux for 18 hours and was run down. The product was taken up in dichloromethane, and the solution was washed successively with saturated aqueous sodium bicarbonate, water, and saturated sodium chloride solution. It was then dried over magnesium sulphate, run down and recrystallised from ethanol to yield 2.3 g of desired product, mp 91°-92° C. The solution was heated at reflux for 18 hours the solution was washed successively with saturated aqueous sodium bicarbonate, water, and saturated sodium chloride solution It was then dried over magnesium sulphate recrystallised from ethanol

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

Procedure: 90.0 mg (0.242 mmol) of 1-[(3-hydroxyazetidin-1-yl)carbonyl]-5-[4-(trifluoromethyl)phenyl]piperidine-3-carboxylic acid (Example 101A) and 34.8 mg (0.266 mmol) of 2-chloro-N′-hydroxybenzenecarboximidamide were reacted according to the General Method 1. Yield: 34.8 mg (27% of theory).

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

Procedure: 100 mg (0.244 mmol) of 1-[(4-cyanopiperidin-1-yl)carbonyl]-5-[4-(trifluoromethyl)phenyl]piperidine-3-carboxylic acid (Example 100A) and 45.8 mg (0.269 mmol) of 2-chloro-N′-hydroxybenzenecarboximidamide were reacted according to the General Method 1. Yield: 72.4 mg (55% of theory).

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

Procedure: 100 mg (0.250 mmol) of 1-[(4-hydroxypiperidin-1-yl)carbonyl]-5-[4-(trifluoromethyl)phenyl]piperidine-3-carboxylic acid (Example 99A) and 46.9 (0.275 mmol) of 2-chloro-N′-hydroxybenzenecarboximidamide were reacted according to the General Method 1. Yield: 53.0 mg (39% of theory).

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

Procedure: 80 mg (0.20 mmol) of 1-(morpholin-4-ylcarbonyl)-5-[4-(trifluoromethoxy)phenyl]piperidine-3-carboxylic acid (Example 44A) and 38 mg (0.22 mmol, 1.1 eq.) of 2-chloro-N′-hydroxybenzenecarboximidamide were reacted according to the General Method 1. Yield: 56 mg (52% of theory)

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

Procedure: 69 mg (0.20 mmol) of 5-(4-ethylphenyl)-1-(morpholin-4-ylcarbonyl)piperidine-3-carboxylic acid (Example 38A) and 38 mg (0.22 mmol, 1.1 eq.) of 2-chloro-N′-hydroxybenzenecarboximidamide were reacted according to the General Method 1. Yield: 49 mg (51% of theory)

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

Procedure: A mixture of 32 g (0.46 moles) hydroxylamine hydrochloride and 49 g (0.46 moles) sodium carbonate in ethanol (about 200 ml) was stirred at room temperature for several minutes; then, 52.4 g (0.381 moles) chlorobenzonitrile was added slowly. The reaction mixture was heated to reflux and allowed to reflux about 6 hours. The reaction mixture was cooled at room temperature and suction-filtered. The solids were washed with acetone. The acetone washings were combined with the filtrate; the combined filtrate-washings were stripped. Acetone (about 200 ml) was added to the residue; the resulting mixture was allowed to sit overnight at room temperature. The mixture was filtered. The filtrate was stripped to give the crude product which was washed with hexane and ethyl ether, suction-filtered, and then air-dried to give the above-identified product as an off-white solid. The reaction mixture was heated to reflux to reflux about 6 hours The reaction mixture was cooled at room temperature suction-filtered The solids were washed with acetone Acetone (about 200 ml) was added to the residue The mixture was filtered to give the crude product which was washed with hexane and ethyl ether suction-filtered air-dried