4,4-difluoro-N-methylcyclohexan-1-amine

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 2,6-dichloro-quinoline-5-carboxylic acid (1500.00 mg; 6.20 mmol; 1.00 eq.), (4,4-difluoro-cyclohexyl)-methylamine (1380.48 mg; 7.44 mmol; 1.20 eq.), (3-dimethylamino-propyl)-ethyl-carbodiimide hydrochloride (1425.53 mg; 7.44 mmol; 1.20 eq.) (EDCI), benzotriazol-1-ol (1004.81 mg; 7.44 mmol; 1.20 eq.) (HOBt) and ethyl-diisopropyl-amine (2402.70 mg; 18.59 mmol; 3.00 eq.) in DMF (10.0 mL) was stirred at room temperature overnight. The mixture was poured into water, the solid was collected by filtration and washed with ethyl acetate, then dried over. The product, 2,6-dichloro-N-((4,4-difluorocyclohexyl)methyl)quinoline-5-carboxamide (1.78 g, 77% yield) was used for the next reaction without further purification. m/z: 374 [M+H]+ the solid was collected by filtration washed with ethyl acetate dried over

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

Procedure: A mixture of 2,6-dichloro-quinoline-5-carboxylic acid (1500.00 mg; 6.20 mmol; 1.00 eq.), (4,4-difluoro-cyclohexyl)-methylamine (1380.48 mg; 7.44 mmol; 1.20 eq.), (3-dimethylamino-propyl)-ethyl-carbodiimide hydrochloride (1425.53 mg; 7.44 mmol; 1.20 eq.) (EDCI), benzotriazol-1-ol (1004.81 mg; 7.44 mmol; 1.20 eq.) (HOBt) and ethyl-diisopropyl-amine (2402.70 mg; 18.59 mmol; 3.00 eq.) in DMF (10.0 mL) was stirred at room temperature overnight. The mixture was poured into water, the solid was collected by filtration and washed with ethyl acetate, then dried over. The product, 2,6-dichloro-N-((4,4-difluorocyclohexyl)methyl)quinoline-5-carboxamide (1.78 g, 77% yield) was used for the next reaction without further purification. m/z: 374 [M+H]+ the solid was collected by filtration washed with ethyl acetate dried over

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

Procedure: The title compound was prepared from 4,4-difluoro-cyclohexanone (prepared from 8,8-Difluoro-1,4-dioxa-spiro[4.5]decane by deprotection with sulfuric acid under standard conditions) and methylamine by reductive amination under standard conditions (Pd hydroxide in methanol, 1 atm hydrogen) in ˜50% yield. Recrystallization of the hydrochloride from ethanol/diethylether afforded analytical pure material. Light-brown solid, mp 137-144° C. MS: m/e=186 (M+H+). Recrystallization of the hydrochloride from ethanol/diethylether afforded analytical pure material

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

Procedure: The title compound was prepared from 4,4-difluoro-cyclohexanone (prepared from 8,8-Difluoro-1,4-dioxa-spiro[4.5]decane by deprotection with sulfuric acid under standard conditions) and methylamine by reductive amination under standard conditions (Pd hydroxide in methanol, 1 atm hydrogen) in ˜50% yield. Recrystallization of the hydrochloride from ethanol/diethylether afforded analytical pure material. Light-brown solid, mp 137–144° C. MS: m/e=186 (M+H+). Recrystallization of the hydrochloride from ethanol/diethylether afforded analytical pure material

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

Procedure: A mixture of 2,6-dichloro-quinoline-5-carboxylic acid (1500.00 mg; 6.20 mmol; 1.00 eq.), (4,4-difluoro-cyclohexyl)-methylamine (1380.48 mg; 7.44 mmol; 1.20 eq.), (3-dimethylamino-propyl)-ethyl-carbodiimide hydrochloride (1425.53 mg; 7.44 mmol; 1.20 eq.) (EDCI), benzotriazol-1-ol (1004.81 mg; 7.44 mmol; 1.20 eq.) (HOBt) and ethyl-diisopropyl-amine (2402.70 mg; 18.59 mmol; 3.00 eq.) in DMF (10.0 mL) was stirred at room temperature overnight. The mixture was poured into water, the solid was collected by filtration and washed with ethyl acetate, then dried over. The product, 2,6-dichloro-N-((4,4-difluorocyclohexyl)methyl)quinoline-5-carboxamide (1.78 g, 77% yield) was used for the next reaction without further purification. m/z: 374 [M+H]+ the solid was collected by filtration washed with ethyl acetate dried over