2,2,2-trifluoroethanamine;hydrochloride

Conditions: temp:120.01; pressure:0.00; stir:

Conditions: temp:120.01; pressure:0.00; stir:

Conditions: temp:120.01; pressure:0.00; stir:

Conditions: temp:120.01; pressure:0.00; stir:

Conditions: temp:120.01; pressure:0.00; stir:

Conditions: temp:120.01; pressure:0.00; stir:

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

Procedure: 2-(4-Nitro-1H-imidazol-1-yl)octanoic acid (7.8 mmoles,2.0 g) was treated with 25 ml oxalyl chloride, concentrated and added to a solution of trifluoroethylamine hydrochloride (7.8 mmoles, 1.06 g) and triethylamine (2 ml) in 50 ml THF. After stirring at room temperature for 16 hours, the mixture was added to ice, extracted with ethyl acetate, dried over sodium sulfate, and concentrated. The intermediate was chromatographed over silica gel to yield 0.6 g of N-(2,2,2-trifluoro)ethyl-2-(4-nitro-1H-imidazol-1-yl)octanoamide. (MS). concentrated the mixture was added to ice extracted with ethyl acetate dried over sodium sulfate concentrated The intermediate was chromatographed over silica gel

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

Procedure: 2,2,2-Trifluoroethylisothiocyanate (2.12 g.) was added to a mixture of 2,2,2-trifluoroethylamine hydrochloride (1.36 g.), triethylamine (1.01 g.) and acetonitrile (10 ml.), and the mixture stirred at room temperature for 4 hours and then evaporated to dryness. The residue was partitioned between water and ethyl acetate, and the ethyl acetate phase was dried and evaporated to dryness. The residue was recrystallised from a mixture of acetone and light petroleum ether (b.p. 60°-80°) to give 1,3-di(2,2,2-trifluoroethyl)thiourea, m.p. 152°-153°. evaporated to dryness The residue was partitioned between water and ethyl acetate the ethyl acetate phase was dried evaporated to dryness The residue was recrystallised from a mixture of acetone and light petroleum ether (b.p. 60°-80°)

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

Procedure: To a solution of 2,2,2-trifluoroethylamine hydrochloride (2.7 grams; 0.02 moles) in tetrahydrofuran (150 ml) and triethylamine (2.8 ml; 0.02 moles) was added acetyl carnitine chloride (4.8 grams; 0.02 moles) in water (10 ml) and lastly N,N'-dicyclohexylcarbodiimide (4.2 grams; 0.02 moles) dissolved in tetrahydrofuran (50 ml). The reaction mixture was kept for a whole day under stirring at room temperature. A precipitate formed. The precipitate consisting of dicyclohexyl urea was filtered and the filtrate was concentrated until complete removal of tetrahydrofuran. The residual aqueous solution was washed with CHCl3 (2×50 ml), then evaporated to dryness. The raw solid was taken up with CH3CN (30 ml), and the resulting mixture was kept at 0° C.-5° C. for 2 hours. After filtering off the unreacted acetyl carnitine, if any, upon addition of ethyl acetate-ethyl ether to the filtrate a product crystallized as a very hygroscopic solid which was stored in a nitrogen atmosphere in anhydrous conditions. The reaction mixture was kept for a whole day A precipitate formed was filtered the filtrate was concentrated until complete removal of tetrahydrofuran The residual aqueous solution was washed with CHCl3 (2×50 ml) evaporated to dryness After filtering off the unreacted acetyl carnitine if any, upon addition of ethyl acetate-ethyl ether to the filtrate a product crystallized as a very hygroscopic solid which

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

Procedure: In 15 ml of water was dissolved 12.55 g of 2,2,2-trifluoroethylamine hydrochloride, followed by addition of 68 ml of CH3CN, and further 9.35 g of Et3N and then 3.00 g (0.0185 mole) of 6-chloro-3-pyridylmethyl chloride under cooling with ice-water and stirring. The mixture was stirred at room temperature for one hour, at 50° C. for one hour and at 70° C. for 90 hours. The CH3CN was distilled off, and the residue was followed by addition of NaHCO3 and then extracted with CH2Cl2 (100 ml×3). The extract was dried over MgSO4 and distilled to remove CH2Cl2. To the residue was added 100 ml of Et2O and the resulting unsoluble matter was filtered off. The filtrate was concentrated to give 3.85 g of the title compound as yellow oil. The mixture was stirred at room temperature for one hour, at 50° C. for one hour and at 70° C. for 90 hours The CH3CN was distilled off the residue was followed by addition of NaHCO3 extracted with CH2Cl2 (100 ml×3) The extract was dried over MgSO4 distilled to remove CH2Cl2 To the residue was added 100 ml of Et2O the resulting unsoluble matter was filtered off The filtrate was concentrated

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

Procedure: In 15 ml of water was dissolved 12.55 g of 2,2,2-trifluoroethylamine hydrochloride, followed by addition of 68 ml of CH3CN, and further 9.35 g of Et3N and then 3.00 g (0.0185 mole) of 6-chloro-3-pyridylmethyl chloride under cooling with ice-water and stirring. The mixture was stirred at room temperature for one hour, at 50° C. for one hour and at 70° C. for 90 hours. The CH3CN was distilled off, and the residue was followed by addition of NaHCO3 and then extracted with CH2Cl2 (100 ml×3). The extract was dried over MgSO4 and distilled to remove CH2Cl2. To the residue was added 100 ml of Et2O and the resulting unsoluble matter was filtered off. The filtrate was concentrated to give 3.85 g of the title compound as yellow oil. The mixture was stirred at room temperature for one hour, at 50° C. for one hour and at 70° C. for 90 hours The CH3CN was distilled off the residue was followed by addition of NaHCO3 extracted with CH2Cl2 (100 ml×3) The extract was dried over MgSO4 distilled to remove CH2Cl2 To the residue was added 100 ml of Et2O the resulting unsoluble matter was filtered off The filtrate was concentrated

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

Procedure: A solution of 7-methylsulphonyl-4-oxo-2-(2-propoxyphenyl)-3,4-dihydropyrimido[4,5-d]pyrimidine (0.72 g), 2,2,2-trifluoroethylamine hydrochloride (0.97 g) and triethylamine (0.73 g) in dichloromethane (15 ml) was stirred at ambient temperature for 48 hours and allowed to stand for 4 days. A yellow solid had formed which was collected by filtration and washed with dichloromethane. The filtrate was washed with dilute hydrochloric acid (15 ml) then water (10 ml) and the aqueous layers extracted with dichloromethane (2×7.5 ml). The combined organic layers were dried (magnesium sulphate) and evaporated under reduced pressure to yield a crude product. This was eluted from a silica column with diethyl ether:chloroform (4:1) and the combined fractions containing product were evaporated under reduced pressure to yield a residue which was recrystallized from isopropanol to yield the title compound, 0.13 g, m.p. 214-215.5° C. A yellow solid had formed which was collected by filtration washed with dichloromethane The filtrate was washed with dilute hydrochloric acid (15 ml) water (10 ml) and the aqueous layers extracted with dichloromethane (2×7.5 ml) The combined organic layers were dried (magnesium sulphate) evaporated under reduced pressure to yield a crude product This was eluted from a silica column with diethyl ether:chloroform (4:1) the combined fractions containing product were evaporated under reduced pressure to yield a residue which was recrystallized from isopropanol