(E)-4-methylpent-2-enoic acid

Conditions: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: (E)-4-Methylpent-2-enoic acid (190 mg, 1.3 mmol) was mixed together with HBTU (470 mg, 1.3 mmol) and N-(2-methyl-4-quinolyl)ethane-1,2-diamine (250 mg, 1.2 mmol) in acetonitrile (5 ml). Triethylamine (1 mll) was added with stirring at 0° C. over 15 minutes and the resulting mixture was stirred at room temperature overnight. The volatiles were removed under reduced pressure, the residue was dissolved in DCM and washed with a saturated solution of sodium bicarbonate. The combined aqueous solutions were extracted three times with DCM. The organic layers were combined, dried over sodium sulfate, the solvent was removed under reduced pressure to give 245 mg of a yellow solid (0.82 mmol, 66%). MS (APCI) m/z=298.2 [M+1]+. the resulting mixture was stirred at room temperature overnight The volatiles were removed under reduced pressure the residue was dissolved in DCM washed with a saturated solution of sodium bicarbonate The combined aqueous solutions were extracted three times with DCM dried over sodium sulfate the solvent was removed under reduced pressure

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

Procedure: (E)-4-Methylpent-2-enoic acid (46 mg, 0.4 mmol), HBTU (152 mg, 0.4 mmol) and triethylamine (82 μl, 0.6 mmol) were dissolved in a 1:1 mixture of anhydrous DMF and anhydrous acetonitrile (2 ml), after 20 minutes N-(5-ethyl-6-methyl-pyrimidin-4-yl)ethane-1,2-diamine hydrochloride (40 mg, 0.185 mmol) was added. The mixture was stirred at room temperature for 2 hours and left to stand at room temperature overnight. The reaction mixture was diluted with ethyl acetate, washed with water, saturated sodium bicarbonate solution and brine, dried over magnesium sulfate and evaporated to dryness under reduced pressure. The residue was purified by preparative HPLC (gradient of water containing 0.1% NH3 and acetonitrile) to yield 9 mg (0.033 mmol, 18%). was added left to stand at room temperature overnight washed with water, saturated sodium bicarbonate solution and brine dried over magnesium sulfate evaporated to dryness under reduced pressure The residue was purified by preparative HPLC (gradient of water containing 0.1% NH3 and acetonitrile) to yield 9 mg (0.033 mmol, 18%)

Conditions: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: (E)-4-Methylpent-2-enoic acid (190 mg, 1.3 mmol) was mixed together with HBTU (470 mg, 1.3 mmol) and N-(2-methyl-4-quinolyl)ethane-1,2-diamine (250 mg, 1.2 mmol) in acetonitrile (5 ml). Triethylamine (1 mll) was added with stirring at 0° C. over 15 minutes and the resulting mixture was stirred at room temperature overnight. The volatiles were removed under reduced pressure, the residue was dissolved in DCM and washed with a saturated solution of sodium bicarbonate. The combined aqueous solutions were extracted three times with DCM. The organic layers were combined, dried over sodium sulfate, the solvent was removed under reduced pressure to give 245 mg of a yellow solid (0.82 mmol, 66%). MS (APCI) m/z=298.2 [M+1]+. the resulting mixture was stirred at room temperature overnight The volatiles were removed under reduced pressure the residue was dissolved in DCM washed with a saturated solution of sodium bicarbonate The combined aqueous solutions were extracted three times with DCM dried over sodium sulfate the solvent was removed under reduced pressure

Conditions: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: (E)-4-Methylpent-2-enoic acid (190 mg, 1.3 mmol) was mixed together with HBTU (470 mg, 1.3 mmol) and N-(2-methyl-4-quinolyl)ethane-1,2-diamine (250 mg, 1.2 mmol) in acetonitrile (5 ml). Triethylamine (1 mll) was added with stirring at 0° C. over 15 minutes and the resulting mixture was stirred at room temperature overnight. The volatiles were removed under reduced pressure, the residue was dissolved in DCM and washed with a saturated solution of sodium bicarbonate. The combined aqueous solutions were extracted three times with DCM. The organic layers were combined, dried over sodium sulfate, the solvent was removed under reduced pressure to give 245 mg of a yellow solid (0.82 mmol, 66%). MS (APCI) m/z=298.2 [M+1]+. the resulting mixture was stirred at room temperature overnight The volatiles were removed under reduced pressure the residue was dissolved in DCM washed with a saturated solution of sodium bicarbonate The combined aqueous solutions were extracted three times with DCM dried over sodium sulfate the solvent was removed under reduced pressure

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

Procedure: (E)-4-Methylpent-2-enoic acid (46 mg, 0.4 mmol), HBTU (152 mg, 0.4 mmol) and triethylamine (82 μl, 0.6 mmol) were dissolved in a 1:1 mixture of anhydrous DMF and anhydrous acetonitrile (2 ml), after 20 minutes N-(5-ethyl-6-methyl-pyrimidin-4-yl)ethane-1,2-diamine hydrochloride (40 mg, 0.185 mmol) was added. The mixture was stirred at room temperature for 2 hours and left to stand at room temperature overnight. The reaction mixture was diluted with ethyl acetate, washed with water, saturated sodium bicarbonate solution and brine, dried over magnesium sulfate and evaporated to dryness under reduced pressure. The residue was purified by preparative HPLC (gradient of water containing 0.1% NH3 and acetonitrile) to yield 9 mg (0.033 mmol, 18%). was added left to stand at room temperature overnight washed with water, saturated sodium bicarbonate solution and brine dried over magnesium sulfate evaporated to dryness under reduced pressure The residue was purified by preparative HPLC (gradient of water containing 0.1% NH3 and acetonitrile) to yield 9 mg (0.033 mmol, 18%)

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

Procedure: (E)-4-Methylpent-2-enoic acid (46 mg, 0.4 mmol), HBTU (152 mg, 0.4 mmol) and triethylamine (82 μl, 0.6 mmol) were dissolved in a 1:1 mixture of anhydrous DMF and anhydrous acetonitrile (2 ml), after 20 minutes N-(5-ethyl-6-methyl-pyrimidin-4-yl)ethane-1,2-diamine hydrochloride (40 mg, 0.185 mmol) was added. The mixture was stirred at room temperature for 2 hours and left to stand at room temperature overnight. The reaction mixture was diluted with ethyl acetate, washed with water, saturated sodium bicarbonate solution and brine, dried over magnesium sulfate and evaporated to dryness under reduced pressure. The residue was purified by preparative HPLC (gradient of water containing 0.1% NH3 and acetonitrile) to yield 9 mg (0.033 mmol, 18%). was added left to stand at room temperature overnight washed with water, saturated sodium bicarbonate solution and brine dried over magnesium sulfate evaporated to dryness under reduced pressure The residue was purified by preparative HPLC (gradient of water containing 0.1% NH3 and acetonitrile) to yield 9 mg (0.033 mmol, 18%)

Conditions: temp:200.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A mixture of 70 g (0.61 mol) of trans-4-methyl-2-pentenoic acid and 49 g (0.72 mol) of 1,3-pentadiene was heated for 12 hours at approx. 200° C. in an autoclave. After the reaction mixture had cooled, it was checked by means of GLC for the presence of 4-methyl-2-pentenoic acid. A further 25 g (0.36 mol) of 1,3-pentadiene were added, after which the mixture was again heated for 12 hours at 200° C. This procedure was repeated until no further decrease in the content of 4-methyl-2-pentenoic acid was any longer observed. The reaction mixture obtained was dissolved in 300 ml of ether and extracted with 300 ml of 10% NaOH solution. The alkaline solution thus obtained was acidified with 40 g of concentrated sulphuric acid and then extracted three times with ether. The ether extract was washed with water, dried on MgSO4, evaporated down and distilled. 73 g of 6-isopropyl-2-methyl-3-cyclohexene-1-carboxylic acid were obtained, b.p.: 95°-100° C./70 Pa. After the reaction mixture had cooled after which the mixture was again heated for 12 hours at 200° C The reaction mixture obtained extracted with 300 ml of 10% NaOH solution The alkaline solution thus obtained extracted three times with ether The ether extract was washed with water dried on MgSO4 evaporated down distilled

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

Procedure: (E)-4-Methylpent-2-enoic acid (26 mg, 0.23 mmol) was dissolved in dichloromethane (1 ml), oxalyl chloride (20 μl, 0.23 mmol) and one drop of DMF were added and the resulting solution was stirred at room temperature for 15 minutes. This solution was added to a solution of 2-methyl-3-(4-piperidyl)pyridine hydrochloride (27 mg, 0.125 mmol) in DCM (2 ml). DIPEA (120 μl, 0.7 mmol) was added and the resulting mixture was stirred at room temperature overnight. The mixture was concentrated under reduced pressure and the resulting residue was purified by preparative HPLC (Waters XBridge, gradient of water containing 0.1% NH3 and acetonitrile) to yield 9.6 mg of a white solid (0.035 mmol, 15%). the resulting mixture was stirred at room temperature overnight The mixture was concentrated under reduced pressure the resulting residue was purified by preparative HPLC (Waters XBridge, gradient of water containing 0.1% NH3 and acetonitrile)

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

Procedure: (E)-4-Methylpent-2-enoic acid (57 mg, 0.5 mmol) was dissolved in dichloromethane (2 ml), oxalyl chloride (42 μl, 0.5 mmol) and one drop of DMF were added and the resulting solution was stirred at room temperature for 15 minutes. This solution was added to a solution of (1S,4S)-5-(2-methyl-3-pyridyl)-2,5-diazabicyclo[2.2.1]heptane hydrochloride (66 mg, 0.3 mmol) in DCM (2 ml). DIPEA (175 μl, 1 mmol) was added and the resulting mixture was stirred at room temperature overnight. The mixture was concentrated under reduced pressure and the resulting residue was purified by preparative HPLC (Waters XBridge, gradient of water containing 0.1% NH3 and acetonitrile) to yield 59 mg of a solid (0.21 mmol, 69%). the resulting mixture was stirred at room temperature overnight The mixture was concentrated under reduced pressure the resulting residue was purified by preparative HPLC (Waters XBridge, gradient of water containing 0.1% NH3 and acetonitrile)

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

Procedure: (E)-4-Methylpent-2-enoic acid (26 mg, 0.23 mmol) was dissolved in dichloromethane (1 ml), oxalyl chloride (20 μl, 0.23 mol) and one drop of DMF were added and the resulting solution was stirred at room temperature for 15 minutes. This solution was added to a solution of 1-(4-methyl-2-pyridyl)-1,4-diazepane dihydrochloride (40 mg, 0.15 mmol) in DCM (2 ml). DIPEA (80 μl, 0.5 mmol) was added and the resulting mixture was stirred at room temperature overnight. The mixture was concentrated under reduced pressure and the resulting residue was purified by preparative HPLC (Waters XBridge, gradient of water containing 0.1% NH3 and acetonitrile) to yield 13 mg of a solid (0.047 mmol, 20%). the resulting mixture was stirred at room temperature overnight The mixture was concentrated under reduced pressure the resulting residue was purified by preparative HPLC (Waters XBridge, gradient of water containing 0.1% NH3 and acetonitrile)

Conditions: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: (E)-4-Methylpent-2-enoic acid (190 mg, 1.3 mmol) was mixed together with HBTU (470 mg, 1.3 mmol) and N-(2-methyl-4-quinolyl)ethane-1,2-diamine (250 mg, 1.2 mmol) in acetonitrile (5 ml). Triethylamine (1 mll) was added with stirring at 0° C. over 15 minutes and the resulting mixture was stirred at room temperature overnight. The volatiles were removed under reduced pressure, the residue was dissolved in DCM and washed with a saturated solution of sodium bicarbonate. The combined aqueous solutions were extracted three times with DCM. The organic layers were combined, dried over sodium sulfate, the solvent was removed under reduced pressure to give 245 mg of a yellow solid (0.82 mmol, 66%). MS (APCI) m/z=298.2 [M+1]+. the resulting mixture was stirred at room temperature overnight The volatiles were removed under reduced pressure the residue was dissolved in DCM washed with a saturated solution of sodium bicarbonate The combined aqueous solutions were extracted three times with DCM dried over sodium sulfate the solvent was removed under reduced pressure

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

Procedure: (E)-4-Methylpent-2-enoic acid (46 mg, 0.4 mmol), HBTU (152 mg, 0.4 mmol) and triethylamine (82 μl, 0.6 mmol) were dissolved in a 1:1 mixture of anhydrous DMF and anhydrous acetonitrile (2 ml), after 20 minutes N-(5-ethyl-6-methyl-pyrimidin-4-yl)ethane-1,2-diamine hydrochloride (40 mg, 0.185 mmol) was added. The mixture was stirred at room temperature for 2 hours and left to stand at room temperature overnight. The reaction mixture was diluted with ethyl acetate, washed with water, saturated sodium bicarbonate solution and brine, dried over magnesium sulfate and evaporated to dryness under reduced pressure. The residue was purified by preparative HPLC (gradient of water containing 0.1% NH3 and acetonitrile) to yield 9 mg (0.033 mmol, 18%). was added left to stand at room temperature overnight washed with water, saturated sodium bicarbonate solution and brine dried over magnesium sulfate evaporated to dryness under reduced pressure The residue was purified by preparative HPLC (gradient of water containing 0.1% NH3 and acetonitrile) to yield 9 mg (0.033 mmol, 18%)