3,3,3-三氟丙烷-1-yne

反应条件: temp:-78.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: 5-[(Benzyloxy)carbonyl]-4,5,6,7-tetrahydro[1,2,3]oxadiazolo[3,4-a]pyrazin-8-ium-3-olate (C58, prepared from 4-[(benzyloxy)carbonyl]piperazine-2-carboxylic acid using the general procedure described by T. S. Mansour et al., 2006, PCT Intl. Appl. WO 2006/130588) (65 g, 0.24 mol) was dissolved in o-xylene (250 mL) and cooled to −78° C. in a bomb reactor. 3,3,3-Trifluoroprop-1-yne (25 g, 0.27 mol) was injected into the reaction mixture, and the bomb was heated to 270° C. for 24 hours. After cooling to room temperature, the reaction was concentrated in vacuo, and the residue was purified by silica gel chromatography to provide C60 as white crystals. Yield: 7.5 g, 23 mmol, 10%. [The major regioisomer, benzyl 2-(trifluoromethyl)-6,7-dihydropyrazolo[1,5-a]pyrazine-5(4H)-carboxylate (C59), was also isolated, in 61% yield.] the bomb was heated to 270° C. for 24 hours After cooling to room temperature the reaction was concentrated in vacuo the residue was purified by silica gel chromatography to provide C60 as white crystals

反应条件: temp:-78.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: 5-[(Benzyloxy)carbonyl]-4,5,6,7-tetrahydro[1,2,3]oxadiazolo[3,4-a]pyrazin-8-ium-3-olate (C58, prepared from 4-[(benzyloxy)carbonyl]piperazine-2-carboxylic acid using the general procedure described by T. S. Mansour et al., 2006, PCT Intl. Appl. WO 2006/130588) (65 g, 0.24 mol) was dissolved in o-xylene (250 mL) and cooled to −78° C. in a bomb reactor. 3,3,3-Trifluoroprop-1-yne (25 g, 0.27 mol) was injected into the reaction mixture, and the bomb was heated to 270° C. for 24 hours. After cooling to room temperature, the reaction was concentrated in vacuo, and the residue was purified by silica gel chromatography to provide C60 as white crystals. Yield: 7.5 g, 23 mmol, 10%. [The major regioisomer, benzyl 2-(trifluoromethyl)-6,7-dihydropyrazolo[1,5-a]pyrazine-5(4H)-carboxylate (C59), was also isolated, in 61% yield.] the bomb was heated to 270° C. for 24 hours After cooling to room temperature the reaction was concentrated in vacuo the residue was purified by silica gel chromatography to provide C60 as white crystals

反应条件: temp:-78.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: 5-[(Benzyloxy)carbonyl]-4,5,6,7-tetrahydro[1,2,3]oxadiazolo[3,4-a]pyrazin-8-ium-3-olate (C58, prepared from 4-[(benzyloxy)carbonyl]piperazine-2-carboxylic acid using the general procedure described by T. S. Mansour et al., 2006, PCT Intl. Appl. WO 2006/130588) (65 g, 0.24 mol) was dissolved in o-xylene (250 mL) and cooled to −78° C. in a bomb reactor. 3,3,3-Trifluoroprop-1-yne (25 g, 0.27 mol) was injected into the reaction mixture, and the bomb was heated to 270° C. for 24 hours. After cooling to room temperature, the reaction was concentrated in vacuo, and the residue was purified by silica gel chromatography to provide C60 as white crystals. Yield: 7.5 g, 23 mmol, 10%. [The major regioisomer, benzyl 2-(trifluoromethyl)-6,7-dihydropyrazolo[1,5-a]pyrazine-5(4H)-carboxylate (C59), was also isolated, in 61% yield.] the bomb was heated to 270° C. for 24 hours After cooling to room temperature the reaction was concentrated in vacuo the residue was purified by silica gel chromatography to provide C60 as white crystals

反应条件: temp:-78.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: 5-[(Benzyloxy)carbonyl]-4,5,6,7-tetrahydro[1,2,3]oxadiazolo[3,4-a]pyrazin-8-ium-3-olate (C58, prepared from 4-[(benzyloxy)carbonyl]piperazine-2-carboxylic acid using the general procedure described by T. S. Mansour et al., 2006, PCT Intl. Appl. WO 2006/130588) (65 g, 0.24 mol) was dissolved in o-xylene (250 mL) and cooled to −78° C. in a bomb reactor. 3,3,3-Trifluoroprop-1-yne (25 g, 0.27 mol) was injected into the reaction mixture, and the bomb was heated to 270° C. for 24 hours. After cooling to room temperature, the reaction was concentrated in vacuo, and the residue was purified by silica gel chromatography to provide C60 as white crystals. Yield: 7.5 g, 23 mmol, 10%. [The major regioisomer, benzyl 2-(trifluoromethyl)-6,7-dihydropyrazolo[1,5-a]pyrazine-5(4H)-carboxylate (C59), was also isolated, in 61% yield.] the bomb was heated to 270° C. for 24 hours After cooling to room temperature the reaction was concentrated in vacuo the residue was purified by silica gel chromatography to provide C60 as white crystals

反应条件: temp:-78.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: 5-[(Benzyloxy)carbonyl]-4,5,6,7-tetrahydro[1,2,3]oxadiazolo[3,4-a]pyrazin-8-ium-3-olate (C58, prepared from 4-[(benzyloxy)carbonyl]piperazine-2-carboxylic acid using the general procedure described by T. S. Mansour et al., 2006, PCT Intl. Appl. WO 2006/130588) (65 g, 0.24 mol) was dissolved in o-xylene (250 mL) and cooled to −78° C. in a bomb reactor. 3,3,3-Trifluoroprop-1-yne (25 g, 0.27 mol) was injected into the reaction mixture, and the bomb was heated to 270° C. for 24 hours. After cooling to room temperature, the reaction was concentrated in vacuo, and the residue was purified by silica gel chromatography to provide C60 as white crystals. Yield: 7.5 g, 23 mmol, 10%. [The major regioisomer, benzyl 2-(trifluoromethyl)-6,7-dihydropyrazolo[1,5-a]pyrazine-5(4H)-carboxylate (C59), was also isolated, in 61% yield.] the bomb was heated to 270° C. for 24 hours After cooling to room temperature the reaction was concentrated in vacuo the residue was purified by silica gel chromatography to provide C60 as white crystals

反应条件: temp:-78.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: 3,3,3-Trifluoro-1-propyne (approx. 0.6 mL, approx. 6 mmol) was condensed in a flame-dried Schlenk tube immersed in a dry ice/acetone bath. Tetrahydrofuran (3 mL) was added followed by a solution of butyllithium in hexanes (2.15 mL, 3.44 mmol, 1.6 M). After stirring 2.5 h at −78° C., zinc chloride (6.87 mL, 3.44 mmol, 0.5 M solution in tetrahydrofuran) was added to the reaction mixture and the reaction vessel was transferred to an ice-water bath and maintained at 0° C. for 30 min. Ethyl 2-ethoxy-4-iodobenzoate (1.00 g, 3.12 mmol, prepared as described in example 14) and tetrakis(triphenylphosphine)palladium(0) (0.18 g, 0.16 mmol) were then added. The reaction vessel was allowed to warm to room temperature and then after 1 h warmed to 50° C. for 18 h. After cooling, the reaction mixture was partitioned between brine (70 mL) and methylene chloride (2×100 mL), dried over magnesium sulfate and evaporated. Purification of the crude residue by flash column chromatography (silica gel, eluting with 1/1 mixture of methylene chloride and hexanes) gave ethyl 4-trifluoroprop-1-ynylbenzoate as an off-white solid (0.474 g, 53%). condensed in a flame-dried Schlenk tube immersed in a dry ice/acetone bath the reaction vessel was transferred to an ice-water bath maintained at 0° C. for 30 min to warm to room temperature after 1 h warmed to 50° C. for 18 h After cooling the reaction mixture was partitioned between brine (70 mL) and methylene chloride (2×100 mL) dried over magnesium sulfate evaporated Purification of the crude residue by flash column chromatography (silica gel, eluting with 1/1 mixture of methylene chloride and hexanes)

反应条件: temp:-78.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: The method is based upon a procedure detailed by Yoneda et al in Bulletin Chemical Society Japan 1990, 63, 2124-2126. A solution of n-butyl lithium (2.5M in hexanes; 1 eq) was added carefully to a solution of 3,3,3-trifluoroprop-1-yne (1 eq) in THF at −78° C. under nitrogen. The mixture was stirred at −78° C. for 30 min then a solution of ZnCl2 (3 eq) in THF was added slowly. The mixture was allowed to warm to room temperature, stirred for 30 min then Pd(Ph3P)4 (5 mol %) was added, followed by 4-iodo-3-methylbenzoic acid (0.5 eq). The mixture was heated to 50° C. and stirred for 15 h, then heated further to 80° C. for 5 h, and finally at 100° C. overnight. After allowing to cool to room temperature the mixture was concentrated under vacuum to a crude residue. The residue was purified by column chromatography on silica gel to give the product as a solid. m/z=227 (M−1). to warm to room temperature stirred for 30 min The mixture was heated to 50° C. stirred for 15 h heated further to 80° C. for 5 h finally at 100° C. overnight to cool to room temperature the mixture was concentrated under vacuum to a crude residue The residue was purified by column chromatography on silica gel

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

实验步骤: The compound was prepared from N-methyl-N-(4-trifluoroacetyl-phenyl)-benzenesulfonamide (Example 22, Step A) and 3,3,3-trifluoroprop-1-yne following the procedure described in Example 29. 1H NMR (CDCl3) δ 3.19 (s, 3 H), 4.30 (br s, 1H), 7.11-7.63 (m, 9 H). Mass Spectrum (CI+) m/e=438 (M+1).

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

实验步骤: The compound was prepared from N-methyl-N-(4-trifluoroacetyl-phenyl)-benzenesulfonamide (Example 22, Step A) and 3,3,3-trifluoroprop-1-yne following the procedure described in Example 29. 1H NMR (CDCl3) δ 3.19 (s, 3H), 4.30 (br s, 1H), 7.11–7.63 (m, 9H). Mass Spectrum (CI+) m/e=438 (M+1).

反应条件: temp:-78.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: 5-[(Benzyloxy)carbonyl]-4,5,6,7-tetrahydro[1,2,3]oxadiazolo[3,4-a]pyrazin-8-ium-3-olate (C58, prepared from 4-[(benzyloxy)carbonyl]piperazine-2-carboxylic acid using the general procedure described by T. S. Mansour et al., 2006, PCT Intl. Appl. WO 2006/130588) (65 g, 0.24 mol) was dissolved in o-xylene (250 mL) and cooled to −78° C. in a bomb reactor. 3,3,3-Trifluoroprop-1-yne (25 g, 0.27 mol) was injected into the reaction mixture, and the bomb was heated to 270° C. for 24 hours. After cooling to room temperature, the reaction was concentrated in vacuo, and the residue was purified by silica gel chromatography to provide C60 as white crystals. Yield: 7.5 g, 23 mmol, 10%. [The major regioisomer, benzyl 2-(trifluoromethyl)-6,7-dihydropyrazolo[1,5-a]pyrazine-5(4H)-carboxylate (C59), was also isolated, in 61% yield.] the bomb was heated to 270° C. for 24 hours After cooling to room temperature the reaction was concentrated in vacuo the residue was purified by silica gel chromatography to provide C60 as white crystals

反应条件: temp:-78.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: 5-[(Benzyloxy)carbonyl]-4,5,6,7-tetrahydro[1,2,3]oxadiazolo[3,4-a]pyrazin-8-ium-3-olate (C58, prepared from 4-[(benzyloxy)carbonyl]piperazine-2-carboxylic acid using the general procedure described by T. S. Mansour et al., 2006, PCT Intl. Appl. WO 2006/130588) (65 g, 0.24 mol) was dissolved in o-xylene (250 mL) and cooled to −78° C. in a bomb reactor. 3,3,3-Trifluoroprop-1-yne (25 g, 0.27 mol) was injected into the reaction mixture, and the bomb was heated to 270° C. for 24 hours. After cooling to room temperature, the reaction was concentrated in vacuo, and the residue was purified by silica gel chromatography to provide C60 as white crystals. Yield: 7.5 g, 23 mmol, 10%. [The major regioisomer, benzyl 2-(trifluoromethyl)-6,7-dihydropyrazolo[1,5-a]pyrazine-5(4H)-carboxylate (C59), was also isolated, in 61% yield.] the bomb was heated to 270° C. for 24 hours After cooling to room temperature the reaction was concentrated in vacuo the residue was purified by silica gel chromatography to provide C60 as white crystals