methyl 2,2,2-trichloroethanimidate

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

Procedure: 1.0 Gram of an o-phenylenediamine compound [compound (207)] of the formula (XII) in which X is H and Z is CF2CF2O was dissolved in 20 ml of acetic acid. 1.4 Grams of methyl trichloroacetoimidate was added thereto at room temperature. The resulting mixture was stirred for 12 hours. The reaction solution was poured into ice water, and precipitated crystals were filtered off. The crystals were dissolved in ethyl acetate. The resulting solution was washed with water and dried over anhydrous sodium sulfate. Removing the solvent from the dried layer by distillation gave 1.0 g of a 2-(trichloromethyl)benzimidazole compound [compound (107)] of the formula (XI) in which X is H and Z is CF2CF2O. at room temperature precipitated crystals were filtered off The crystals were dissolved in ethyl acetate The resulting solution was washed with water dried over anhydrous sodium sulfate Removing the solvent from the dried layer by distillation

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

Procedure: 8.6 Grams of an o-phenylenediamine compound [compound (204)] of the formula (XII) in which X is H and Z is OCF2O was dissolved in 80 ml of acetic acid. 8.7 Grams of methyl trichloroacetoimidate was added thereto at room temperature. The resulting mixture was stirred for 20 minutes. The reaction solution was poured into ice water, and precipitated crystals were filtered off. The crystals were dissolved in ethyl acetate. The resulting solution was washed with water and dried over anhydrous sodium sulfate. Removing the solvent from the dried layer by distillation gave 5.35 g of a 2-(trichloromethyl)benzimidazole compound [compound (104)] of the formula (XI) in which X is H and Z is OCF2O. at room temperature precipitated crystals were filtered off The crystals were dissolved in ethyl acetate The resulting solution was washed with water dried over anhydrous sodium sulfate Removing the solvent from the dried layer by distillation

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

Procedure: 8.6 Grams of an o-phenylenediamine compound [compound (204)] of the formula (XII) in which X is H and Z is OCF2O was dissolved in 80 ml of acetic acid. 8.7 Grams of methyl trichloroacetoimidate was added thereto at room temperature. The resulting mixture was stirred for 20 minutes. The reaction solution was poured into ice water, and precipitated crystals were filtered off. The crystals were dissolved in ethyl acetate. The resulting solution was washed with water and dried over anhydrous sodium sulfate. Removing the solvent from the dried layer by distillation gave 5.35 g of a 2-(trichloromethyl)benzimidazole compound [compound (104)] of the formula (XI) in which X is H and Z is OCF2O. at room temperature precipitated crystals were filtered off The crystals were dissolved in ethyl acetate The resulting solution was washed with water dried over anhydrous sodium sulfate Removing the solvent from the dried layer by distillation

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

Procedure: 2.5 Grams of an o-phenylenediamine compound [compound (201)] of the formula (XII) in which X is H and Z is OCF2CFHO was dissolved in 50 ml of acetic acid. 3.8 Grams of methyl trichloroacetoimidate was added thereto at room temperature. The resulting mixture was stirred for 1 hour. The reaction solution was poured into ice water, and precipitated crystals were filtered off. The crystals were dissolved in ethyl acetate. The resulting solution was washed with water and dried over anhydrous sodium sulfate. Removing the solvent from the dried layer by distillation gave 3.2 g of a 2-(trichloromethyl)benzimidazole compound [compound (101)] of the formula (XI) in which X is H and Z is OCF2CFHO. at room temperature precipitated crystals were filtered off The crystals were dissolved in ethyl acetate The resulting solution was washed with water dried over anhydrous sodium sulfate Removing the solvent from the dried layer by distillation

Conditions: temp:60.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Formic acid (2.8 mL) and trifluoroethanol (61 mL) were added to (R)-(1-(5,6-diaminopyridin-2-yl)piperidin-3-yl)(pyrrolidin-1-yl)methanone dihydrochloride. Methyl 2,2,2-trichloroacetimidate (1.65 mL) was added and the reaction mixture was stirred at 60° C. for 3 h. The mixture was used for the next step without further workup or purification. The mixture was used for the next step without further workup or purification

Conditions: temp:60.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Formic acid (2.8 mL) and trifluoroethanol (61 mL) were added to (R)-(1-(5,6-diaminopyridin-2-yl)piperidin-3-yl)(pyrrolidin-1-yl)methanone dihydrochloride. Methyl 2,2,2-trichloroacetimidate (1.65 mL) was added and the reaction mixture was stirred at 60° C. for 3 h. The mixture was used for the next step without further workup or purification. The mixture was used for the next step without further workup or purification

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

Procedure: Into a vial containing (R)-(1-(5,6-diaminopyridin-2-yl)piperidin-3-yl)(pyrrolidin-1-yl)methanone dihydrochloride (125 mg, 0.3 mmol) was added formic acid (73.5 μL, 1.7 mmol) followed by 2,2,-trifluoroethanol (1.7 mL) and methyl 2,2,2-trichloroacetimidate (47.0 μL, 0.4 mmol). The vial was sealed and stirred at room temperature for 13 min. The reaction mixture was heated to 60° C. and stirred for 3 h at that temperature. An aliquot of 0.3 mL was transferred into another vial containing diethylamine (89.1 μL, 0.9 mmol). The resulting mixture was heated to 60° C. and stirred for 16 h. The reaction mixture was concentrated under reduced pressure and the resulting residue was partitioned between water and ethyl acetate. The aqueous was further extracted with ethyl acetate. The combined organics were concentrated under reduced pressure. The residue was purified via HPLC to afford the title compound. MS (ESI+) (M+H) 399.1; HPLC retention time 1.9864 min (Method A). The vial was sealed The reaction mixture was heated to 60° C. stirred for 3 h at that temperature The resulting mixture was heated to 60° C. stirred for 16 h The reaction mixture was concentrated under reduced pressure the resulting residue was partitioned between water and ethyl acetate The aqueous was further extracted with ethyl acetate The combined organics were concentrated under reduced pressure The residue was purified via HPLC

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

Procedure: A mixture of 4.2 g (0.07 mole) formylhydrazine and 20 ml (28.5 g, 0.16 mole) methyl 2,2,2-trichloroacetimidate was stirred at room temperature. After 10 minutes a vigorous reaction occurred and the temperature rose to 65° C. The beige solid that formed was washed with petroleum ether and dried to give 11.0 g [77%, mp 124°-126° C. (decomposed)] of product. An analytical sample was recrystallized from toluene [mp 128°-130° C. (decomposed)]. The structure was confirmed via infrared and elemental analysis. After 10 minutes a vigorous reaction rose to 65° C The beige solid that formed was washed with petroleum ether dried to give 11.0 g [77%, mp 124°-126° C. (decomposed)] of product An analytical sample was recrystallized from toluene [mp 128°-130° C. (decomposed)]

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

Procedure: A mixture of 2.9 g (0.025 mole) t-butyl carbazate and 10 ml (14.3 g, 0.08 mole) methyl 2,2,2-trichloroacetimidate was stirred 16 hours at room temperature. The solid that was left was washed with petroleum ether and dried to give 6.0 g (86% yield mp 150° C.). The structure was confirmed via infrared and elemental analysis. The solid that was left was washed with petroleum ether dried to give 6.0 g (86% yield mp 150° C.)

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

Procedure: A mixture of 2.9 g (0.025 mole) t-butyl carbazate and 10 ml (14.3 g, 0.08 mole) methyl 2,2,2-trichloroacetimidate was stirred 16 hours at room temperature. The solid that was left was washed with petroleum ether and dried to give 6.0 g (86% yield mp 150° C.). The structure was confirmed via infrared and elemental analysis. The solid that was left was washed with petroleum ether dried to give 6.0 g (86% yield mp 150° C.)

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

Procedure: A mixture of 3.8 g (0.025 mole) salicoylhydrazine and 10 ml (14.3 g, 0.08 mole) methyl 2,2,2-trichloroacetimidate was stirred 16 hours at room temperature. The solid that formed was washed with petroleum ether and dried to give 7.5 g (100% Yield; mp 168°-169° C.). The structure was confirmed via infrared and elemental analysis. The solid that formed was washed with petroleum ether dried to give 7.5 g (100% Yield; mp 168°-169° C.)

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

Procedure: A mixture of 5.0 g (0.07 mole) acetylhydrazine and 20 ml (28.5 g, 0.16 mole) methyl 2,2,2-trichloroacetimidate was stirred 16 hours at room temperature. The resulting solid was recrystallized from toluene to yield 7.3 g. Addition of petroleum ether to the filtrate gave another 1.5 g. The total yield was 8.8 g (59%; mp 130°-132° C.). An analytical sample (mp 131°-132° C.) was prepared by recrystallization from toluene. The structure was confirmed via infrared and elemental analysis. The resulting solid was recrystallized from toluene to yield 7.3 g gave another 1.5 g