2,2,2-三氟乙烷-1-磺酰胺

反应条件: temp:0.00; pressure:0.00; stir:

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: In the same manner as in Example 1, step 6 and using 7-(2-methylphenylamino)-6-(4-phenylpiperidine-1-carbonyl)pyrazolo[1,5-a]pyrimidine-3-carboxylic acid (0.12 g, 0.27 mmol) obtained in Example 39, step 2 and 2,2,2-trifluoroethanesulfonamide (WO1984/02650, 0.21 g, 1.33 mmol), the title compound (0.07 g, 43%) was obtained.

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: To a solution of O-protected trifluoroethyl piperidine (1.13 g, 3.6 mmol) in DCE (15 mL) was added triethylamine (0.6 mL, 4.3 mmol) then 4-chlorobenzenesulfonyl chloride (1.13 g, 5.4 mmol) and the reaction mixture was heated at reflux overnight. The final mixture was concentrated and directly purified by flash chromatography over silica gel (eluting with hexane to DCM) to afford 0.67 g (38%) of O-protected trifluoroethyl sulfonamide. at reflux overnight The final mixture was concentrated directly purified by flash chromatography over silica gel (eluting with hexane to DCM)

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: The CF3CH2SO2NH2 was prepared by cooling a solution of commercially available CF3CH2SO2Cl (0.6 ml, 1 eq) in CH2Cl2 to 0° C. NH4OH (0.75 ml, 14.8 N, 2 eq) was then added dropwise. The mixture was allowed to warm to room temperature overnight. The reaction was diluted with water and extracted three times with CH2Cl2. The combined organic layers were dried with Na2SO4 and concentrated. The sulfonamide was used without further purification. extracted three times with CH2Cl2 The combined organic layers were dried with Na2SO4 concentrated The sulfonamide was used without further purification

反应条件: temp:0.00; pressure:0.00; stir:

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: The CF3CH2SO2NH2 was prepared by cooling a solution of commercially available CF3CH2SO2Cl (0.6 ml, 1 eq) in CH2Cl2 to 0° C. NH4OH (0.75 ml, 14.8 N, 2 eq) was then added dropwise. The mixture was allowed to warm to room temperature overnight. The reaction was diluted with water and extracted three times with CH2Cl2. The combined organic layers were dried with Na2SO4 and concentrated. The sulfonamide was used without further purification. extracted three times with CH2Cl2 The combined organic layers were dried with Na2SO4 concentrated The sulfonamide was used without further purification

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: Prepared by coupling 1a and 2,2,2-trifluoroethanesulfonamide (Synlett, 1997, 375) in accordance with Procedure 1, Method A described hereinabove. Yield (34%); 1H NMR (d6-DMSO) δ 7.39-7.01 (m, 13H), 6.83 (d, J=8.1 Hz, 2H), 6.40 (d, J=15.7 Hz, 1H), 2.85 (s, 1H), 2.69 (s, 1H), 2.36 (q, J=7.3 Hz, 2H), 0.83 (t, J=7.3 Hz, 3H); ESI m/z: 498 (M−H−). Prepared Yield (34%)

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: Prepared by coupling 1a and 2,2,2-trifluoroethanesulfonamide (Synlett, 1997, 375) in accordance with Procedure 1, Method A described hereinabove. Yield (34%); 1H NMR (d6-DMSO) δ 7.39–7.01 (m, 13H), 6.83 (d, J=8.1 Hz, 2H), 6.40 (d, J=15.7 Hz, 1H), 2.85 (s, 1H), 2.69 (s, 1H), 2.36 (q, J=7.3 Hz, 2H), 0.83 (t, J=7.3 Hz, 3H); ESI m/z: 498 (M−H−). Prepared Yield (34%)

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: A solution of [6-(4-cyanophenyl)-5-(2-furoyl)-4-methyl-2-oxo-3-[3-(trifluoromethyl)phen-yl]-3,6-dihydropyrimidin-1(2H)-yl]acetic acid (Example 29A) (75 mg, 0.15 mmol), 2,2,2-trifluoroethane-sulfonamide (23 mg, 0.16 mmol), 1,3-dicyclohexylcarbodiimide (33 mg, 0.16 mmol) and 4-dimethylaminopyridine (20 mg, 0.16 mmol) in dichloromethane (4 ml) is stirred at room temperature for 4 days. The product is extracted with dichloromethane (100 ml), washed with 2 N hydrochloric acid and brine, dried over magnesium sulfate, filtered and concentrated in vacuo. The residue is purified by preparative HPLC(RP18 column; eluent: acetonitrile/0.1% aq. formic acid 30:70→90:10). The title compound is isolated as a colourless solid. The product is extracted with dichloromethane (100 ml) washed with 2 N hydrochloric acid and brine dried over magnesium sulfate filtered concentrated in vacuo The residue is purified by preparative HPLC(RP18 column

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: The CF3CH2SO2NH2 was prepared by cooling a solution of commercially available CF3CH2SO2Cl (0.6 ml, 1 eq) in CH2Cl2 to 0° C. NH4OH (0.75 ml, 14.8 N, 2 eq) was then added dropwise. The mixture was allowed to warm to room temperature overnight. The reaction was diluted with water and extracted three times with CH2Cl2. The combined organic layers were dried with Na2SO4 and concentrated. The sulfonamide was used without further purification. extracted three times with CH2Cl2 The combined organic layers were dried with Na2SO4 concentrated The sulfonamide was used without further purification

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: A solution of [6-(4-cyanophenyl)-5-(2-furoyl)-4-methyl-2-oxo-3-[3-(trifluoromethyl)phenyl]-3,6-dihydropyrimidin-1(2H)-yl]acetic acid (Example 29A) (75 mg, 0.15 mmol), 2,2,2-trifluoroethane-sulfonamide (23 mg, 0.16 mmol), 1,3-dicyclohexylcarbodiimide (33 mg, 0.16 mmol) and 4-dimethylaminopyridine (20 mg, 0.16 mmol) in dichloromethane (4 ml) is stirred at room temperature for 4 days. The product is extracted with dichloromethane (100 ml), washed with 2 N hydrochloric acid and brine, dried over magnesium sulfate, filtered and concentrated in vacuo. The residue is purified by preparative HPLC (RP18 column; eluent: acetonitrile/0.1% aq. formic acid 30:70→90:10). The title compound is isolated as a colourless solid. The product is extracted with dichloromethane (100 ml) washed with 2 N hydrochloric acid and brine dried over magnesium sulfate filtered concentrated in vacuo The residue is purified by preparative HPLC (RP18 column; eluent: acetonitrile/0.1% aq. formic acid 30:70→90:10)

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: The CF3CH2SO2NH2 was prepared by cooling a solution of commercially available CF3CH2SO2Cl (0.6 ml, 1 eq) in CH2Cl2 to 0° C. NH4OH (0.75 ml, 14.8 N, 2 eq) was then added dropwise. The mixture was allowed to warm to room temperature overnight. The reaction was diluted with water and extracted three times with CH2Cl2. The combined organic layers were dried with Na2SO4 and concentrated. The sulfonamide was used without further purification. extracted three times with CH2Cl2 The combined organic layers were dried with Na2SO4 concentrated The sulfonamide was used without further purification