N'-hydroxy-2-methylpropanimidamide

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

Procedure: The title compound was prepared by following the procedure as described for Example-40 by using methyl 4-(3-(2,6-dichlorophenyl)-5-oxo-4,5-dihydro-1H-1,2,4-triazol-1-yl)-2-methoxybenzoate (Intermediate-21, 0.100 g, 0.25 mmol), N′-hydroxyisobutyrimidamide (0.077 g, 0.529 mmol), sodium hydride (0.020 g, 0.50 mmol) and dry THF (5.0 mL) at RT to afford 0.019 g of desired product. 1HNMR (DMSO-d6): δ 1.31 (d, J=6.9 Hz, 6H), 3.12 (m, 1H), 3.95 (s, 3H), 7.65-7.78 (m, 4H), 7.56 (s, 1H), 8.09 (d, J=8.7 Hz, 1H), 12.83 (br s, 1H); MS (m/z): 447.96 [M+H]+. The title compound was prepared at RT

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

Procedure: The title compound was prepared by following the procedure as described for Example-40 by using methyl 4-(3-(2,6-dichlorophenyl)-5-oxo-4,5-dihydro-1H-1,2,4-triazol-1-yl)-2-methoxybenzoate (Intermediate-21, 0.100 g, 0.25 mmol), N′-hydroxyisobutyrimidamide (0.077 g, 0.529 mmol), sodium hydride (0.020 g, 0.50 mmol) and dry THF (5.0 mL) at RT to afford 0.019 g of desired product. 1HNMR (DMSO-d6): δ 1.31 (d, J=6.9 Hz, 6H), 3.12 (m, 1H), 3.95 (s, 3H), 7.65-7.78 (m, 4H), 7.56 (s, 1H), 8.09 (d, J=8.7 Hz, 1H), 12.83 (br s, 1H); MS (m/z): 447.96 [M+H]+. The title compound was prepared at RT

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

Procedure: The title compound was prepared by following the procedure as described for Example-40 by using methyl 4-(3-(2,6-dichlorophenyl)-5-oxo-4,5-dihydro-1H-1,2,4-triazol-1-yl)-2-methoxybenzoate (Intermediate-21, 0.100 g, 0.25 mmol), N′-hydroxyisobutyrimidamide (0.077 g, 0.529 mmol), sodium hydride (0.020 g, 0.50 mmol) and dry THF (5.0 mL) at RT to afford 0.019 g of desired product. 1H NMR (DMSO-d6): 1.31 (d, J=6.9 Hz, 6H), 3.12 (m, 1H), 3.95 (s, 3H), 7.65-7.78 (m, 4H), 7.56 (s, 1H), 8.09 (d, J=8.7 Hz, 1H), 12.83 (br s, 1H); MS (m/z): 447.96 [M+H]+. The title compound was prepared at RT

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

Procedure: The title compound was prepared by following the procedure as described for Example-40 by using methyl 4-(3-(2,6-dichlorophenyl)-5-oxo-4,5-dihydro-1H-1,2,4-triazol-1-yl)-2-methoxybenzoate (Intermediate-21, 0.100 g, 0.25 mmol), N′-hydroxyisobutyrimidamide (0.077 g, 0.529 mmol), sodium hydride (0.020 g, 0.50 mmol) and dry THF (5.0 mL) at RT to afford 0.019 g of desired product. 1H NMR (DMSO-d6): 1.31 (d, J=6.9 Hz, 6H), 3.12 (m, 1H), 3.95 (s, 3H), 7.65-7.78 (m, 4H), 7.56 (s, 1H), 8.09 (d, J=8.7 Hz, 1H), 12.83 (br s, 1H); MS (m/z): 447.96 [M+H]+. The title compound was prepared at RT

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

Procedure: A solution of (2R)-2-[2-(tert-butoxy)-2-oxoethyl]-5-cyclohexylpentanoic acid (Preparation 1) (500 mg, 1.70 mmol) in dichloromethane (30 ml) was treated with 1,1′-carbonyldiimidazole (272 mg, 1.70 mol) and the solution was stirred at room temperature for 1 hour. The N′-hydroxy-2-methylpropanimidamide (Monatsh.Chem.; 113; 1982; 781-792) (174 mg, 1.70 mmol) was then added and the mixture was stirred for 30 minutes. The solvent was removed under reduced pressure and the residue was heated neat at 120° C. under a nitrogen atmosphere for 18 hours. The crude product was then purified by column chromatography on silica gel eluting with dichloromethane to afford the title compound as a colourless oil (250 mg). the mixture was stirred for 30 minutes The solvent was removed under reduced pressure the residue was heated neat at 120° C. under a nitrogen atmosphere for 18 hours The crude product was then purified by column chromatography on silica gel eluting with dichloromethane

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

Procedure: The compound was synthesized as described in Example 17 using 1,6-dimethyl-3-ethoxycarbonyl-1,2,5,6-tetrahydropyridinium oxalate (Bishop, Z. Naturforsch. 25b, 1249-1251 (1970)) and acetamide oxime instead of arecoline, HBr and isopropylcarboxamide oxime, respectively. M.P. 115°-117° C. The compound was synthesized

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

Procedure: The compound was synthesized as described in Example 17 using (RS)-3-methoxycarbonyl-5-methyl-1,2,5,6-tetrahydropyridinium oxalate and propionamide oxime instead of arecoline, HBr and isopropylcarboxamide oxime, respectively. M.P. 188°-189° C. The compound was synthesized

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

Procedure: 2 g of ethyl 4-trifluoromethylpyrimidine-5-carboxylate and 1.56 g of isobutyramide oxime were initially charged in 15 ml of ethanol and cooled to 0° C. 10 ml of a 1.2 molar sodium ethoxide solution were added dropwise to this solution. The mixture was allowed to warm to room temperature over a period of one hour and then heated under reflux until the reaction, according to TLC, had ended. The reaction mixture was concentrated and the residue was taken up in saturated ammonium chloride solution and extracted with diethyl ether. Chromatographic purification of the crude product gave the desired compound as a yellowish oil. to warm to room temperature over a period of one hour heated under reflux until the reaction The reaction mixture was concentrated extracted with diethyl ether Chromatographic purification of the crude product

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

Procedure: 2 g of methyl 4-trifluoromethylnicotinate and 1.56 g of isobutyramide oxime were initially charged in 15 ml of ethanol and cooled to 0° C. 10 ml of a 1.2 molar sodium ethoxide solution were added dropwise to this solution. The mixture was allowed to warm to room temperature over a period of two hours and stirring was then continued at this temperature until the reaction, according to TLC, had ended. The reaction mixture was concentrated and the residue was taken up in saturated ammonium chloride solution and extracted with diethyl ether. Chromatographic purification of the crude product gave the desired compound as a yellowish oil. to warm to room temperature over a period of two hours was then continued at this temperature until the reaction The reaction mixture was concentrated extracted with diethyl ether Chromatographic purification of the crude product

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

Procedure: The compound was synthesized as described in Example 17 using 1,6-dimethyl-3-ethoxycarbonyl-1,2,5,6-tetrahydropyridinium oxalate (Bishop, Z. Naturforsch. 25b, 1249-1251 (1970)) and acetamide oxime instead of arecoline, HBr and isopropylcarboxamide oxime, respectivelY. M.P. 115°-117° C. The compound was synthesized

Conditions: temp:80.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 816 mg(8.0 mmol) of isopropylcarboxamide oxime was added to a solution of sodium ethoxide (7.8 mmol) in 20 ml of distilled ethanol and 5 g molecular sieves. The mixture was stirred at room temperature for 10 min whereafter 1.0 g(4.23 mmol) of arecoline, HBr was added. The mixture was heated at 80° C. for 12 hours, filtered, and evaporated in vacuo. 10 ml of water was added to the residue and the mixture was extracted with ether (3×50 ml). The combined extracts were dried with MgSO4 and evaporated in vacuo. The residue was dissolved in 5 ml of 99.9% ethanol and a solution of 380 mg(4.23 mmol) of oxalic acid in 10 ml of 99.9% ethanol was added. Crystallization from ether gave the title compound in 37% yield. M.P. 133°-134° C. was added filtered evaporated in vacuo 10 ml of water was added to the residue the mixture was extracted with ether (3×50 ml) The combined extracts were dried with MgSO4 evaporated in vacuo The residue was dissolved in 5 ml of 99.9% ethanol Crystallization from ether

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

Procedure: Under nitrogen atmosphere, to a solution of N′-hydroxyisobutyrimidamide (0.028 g, 0.268 mmol) in THF was added sodium hydride (0.021 g, 0.51 mmol). The reaction mass was refluxed for 15-20 minutes. Then added methyl 2-((2-chloro-6-fluorophenyl)amino)-7,7-dimethyl-7,8-dihydro-1H-benzofuro[4,5-d]imidazole-5-carboxylate (Step-1 of Intermediate-15, 0.100 g, 0.255 mmol) and continued reflux for 4-5 h. The reaction mass was diluted with water and extracted with ethyl acetate. The organic layer was dried over anhydrous sodium sulphate and concentrated. The obtained crude was purified column chromatography to afford 0.020 g of the desired product. 1HNMR (DMSO-d6): δ 1.28 (d, 6H), 1.48 (s, 6H), 3.09 (m, 3H), 7.24 (m, 1H), 7.39 (m, 1H), 7.54 (d, J=7.2 Hz, 1H), 9-10 (s, 1H), 10.5 (s, 1H); MS [M]+: 458.14. The reaction mass was refluxed for 15-20 minutes extracted with ethyl acetate The organic layer was dried over anhydrous sodium sulphate concentrated The obtained crude was purified column chromatography