N,N-dimethylcyclohexanamine

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:

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:65.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A one-liter, 3-necked, Morton flask equipped with an air condenser and a magnetic stirring plate was charged with N,N-dimethylcyclohexylamine (210.06 grams, 1.65 moles), 1-bromo-3-chloropropane (259.99 grams, 1.65 moles) and methanol (250 mL). Reaction was maintained at 65° C. for 24 hours. Methanol was removed by rotary evaporation under reduced pressure to yield a brown sludge. To the sludge was added tert-butylmethylether (600 ml) causing an oil to form. The liquid phase was decanted from the oil and a second portion of methyl-tert-butylether (600 ml) was added. The mixture was stirred and liquid phase was decanted off from a thick sludge. To the sludge was added diethylether (600 mL) causing a white, semi-solid layer to form. The mixture was stirred and a liquid phase was removed. A white solid was placed in a vacuum oven at 35° C. for 24 hours. Yield 404.9 grams (1.42 molest 85%) A one-liter, 3-necked, Morton flask equipped with an air condenser Reaction Methanol was removed by rotary evaporation under reduced pressure to yield a brown sludge to form The liquid phase was decanted from the oil a second portion of methyl-tert-butylether (600 ml) was added liquid phase was decanted off from a thick sludge To the sludge was added diethylether (600 mL) to form The mixture was stirred a liquid phase was removed

Conditions: temp:195.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Phosphorus pentoxide (7.55 g, 53.2 mmol), N,N-dimethylcyclohexylamine (17 ml, 113 mmol) and 1,2-dimethylpropylamine hydrochloride (12.4 g, 100.4 mmol) were carefully mixed and heated with mechanical stirring on an oil bath at 190-200° C. for about 15 min. To the homogeneous mass was added 6-chloro-3,4-dihydro-3-oxo-1,2,4-benzothiadiazine 1,1-dioxide (5.84 g, 25.1 mmol) and the mixture was stirred at 235° C. for 2 h. After cooling to about 100° C., water (200 ml) was added and the dark mixture was hydrolysed by stirring over night at room temperature. The precipitate was isolated by filtration and recrystallised from ethanol with decolorising charcoal to give 2,83 g (37%) of the pure title compound; m.p. (DSC) 264.7° C.; 1H-NMR (DMSO-d6): δ 0.90 (dd, 6H, CH(CH3)2), 1.09 (d, 3H, NCHCH3), 1.76 (m, 1H, CH(CH3)2), 3.70 (m, 1H, NHCH), 7.15 (br., 1H, NH), 7.28 (m, 2H, ArH), 7.68 (d, 1H, ArH), 10.3 (br.s, 1H, NH); (C12H16N3Cl1O2S1) calc. C, 47.76; H, 5.34; N 13.92; found C, 47.66; H, 5.47; N, 13.91. heated the mixture was stirred at 235° C. for 2 h After cooling to about 100° C. by stirring over night at room temperature The precipitate was isolated by filtration recrystallised from ethanol with decolorising charcoal

Conditions: temp:110.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 10 g of 3,5-bis(trifluoromethyl)bromobenzene are mixed with 11 ml of cyclohexyldimethylamine and 30 ml of dimethylacetamide and degassed. 38 mg of palladium acetate and 152 mg of di(tert-butyl)phenylphosphine are dissolved in 5 ml of dimethylacetamide and added to the mixture. The mixture is transferred to an autoclave and 30 bar of ethylene are injected. The mixture is then heated to 110° C. and stirred at this temperature for 3 hours. At the end of the reaction, the mixture is cooled and the pressure released. Subsequently, 8.3 g of 1,5-dimethyl-3-trifluoromethyl-1H-pyrazole are added to the reaction mixture and the mixture is heated to 130° C. for 12 h. Afterwards, the mixture is cooled, added to water and worked up with toluene. Yield over the two steps: 10.5 g (76%) of slightly brownish solid. degassed 38 mg of palladium acetate and 152 mg of di(tert-butyl)phenylphosphine are dissolved in 5 ml of dimethylacetamide added to the mixture At the end of the reaction the mixture is cooled the mixture is heated to 130° C. for 12 h Afterwards, the mixture is cooled Yield over the two steps

Conditions: temp:110.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 183 mg (0.983 mmol) of 4-ethinyl-1,5-dimethyl-3-(trifluoromethyl)-1H-pyrazole, 2.3 mg (0.01 mmol) of palladium acetate and 3.9 mg (0.02 mmol) of copper(I) iodide are weighed into a round-bottom flask and placed under protective gas. Subsequently, 9.1 mg (0.04 mmol) of di(tert-butyl)phenylphosphine, 300 mg (1.03 mmol) of 3,5-bis(trifluoromethyl)bromobenzene, 137 mg (1.08 mmol) of cyclohexyldimethylamine and dimethylacetamide (5 ml) are added and the mixture is heated to 110° C. for 12 h. After the end of the reaction, the mixture is cooled, poured onto cold, dilute hydrochloric acid and extracted with ether. The combined ether phases which have been dried over MgSO4 are concentrated. The product is obtained as a solid in an 85% yield. After the end of the reaction the mixture is cooled extracted with ether The combined ether phases which have been dried over MgSO4 are concentrated The product is obtained as a solid in an 85% yield

Conditions: temp:110.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 183 mg (0.983 mmol) of 4-ethinyl-1,5-dimethyl-3-(trifluoromethyl)-1H-pyrazole, 2.3 mg (0.01 mmol) of palladium acetate and 3.9 mg (0.02 mmol) of copper(I) iodide are weighed into a round-bottom flask and placed under protective gas. Subsequently, 9.1 mg (0.04 mmol) of di(tert-butyl)phenylphosphine, 300 mg (1.03 mmol) of 3,5-bis(trifluoromethyl)bromobenzene, 137 mg (1.08 mmol) of cyclohexyldimethylamine and dimethylacetamide (5 ml) are added and the mixture is heated to 110° C. for 12 h. After the end of the reaction, the mixture is cooled, poured onto cold, dilute hydrochloric acid and extracted with ether. The combined ether phases which have been dried over MgSO4 are concentrated. The product is obtained as a solid in an 85% yield. After the end of the reaction the mixture is cooled extracted with ether The combined ether phases which have been dried over MgSO4 are concentrated The product is obtained as a solid in an 85% yield