pentane-1-thiol

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

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

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

Procedure: A mixture of 6-chloro-3-propyl-1-[[2'-(N-trityltetrazol-5-yl)biphenyl-4-yl]methyl]pyrimidine-2,4(1H,3H)-dione (0.5 g), pentylmercaptan (0.12 ml) and potassium carbonate (0.13 g) in acetonitrile (10 ml) was heated under reflux for 4 hours with stirring. The reaction mixture was allowed to cool and the precipitate was removed by filtration. The filtrate was concentrated to dryness. The resulting residue was dissolved in methanol (15 ml) and then 1N hydrochloric acid (1.5 ml) was added to the solution, followed by stirring at room temperature for 2 hours. The reaction mixture was concentrated to dryness and then the residue was extracted with methylene chloride-water. The organic layer was washed with water, dried, and evaporated to dryness. The resulting residue was purified by column chromatography on silica gel to give colorless amorphous powders (0.16 g, 43%). was heated under reflux for 4 hours to cool the precipitate was removed by filtration The filtrate was concentrated to dryness The resulting residue was dissolved in methanol (15 ml) 1N hydrochloric acid (1.5 ml) was added to the solution by stirring at room temperature for 2 hours The reaction mixture was concentrated to dryness the residue was extracted with methylene chloride-water The organic layer was washed with water dried evaporated to dryness The resulting residue was purified by column chromatography on silica gel

Conditions: temp:-78.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A suspension of sodium hydride (4.0 g, 100 mmole) in dry tetrahydrofuran (350 mL) under a nitrogen atmosphere was cooled in an ice bath. Pentyl mercaptan (10.8 g, 100 mmole) was added dropwise over 10 minutes. The resulting suspension of sodium alkylmercaptide was added in portions over 30 minutes to a stirred solution of 1-chloro-3-iodopropane (20.44 g, 100 mmole) in tetrahydrofuran (450 mL) that had been cooled to -78° C. The mixture was allowed to warm to ambient temperature overnight, then washed with brine, dried over MgSO4, and concentrated under vacuum. The resultant oil was distilled under water aspirator pressure to yield the desired product (10.67 g, 59% yield), b.p. 113°-119° C. (20 mm Hg). was cooled in an ice bath to warm to ambient temperature overnight washed with brine dried over MgSO4 concentrated under vacuum The resultant oil was distilled under water aspirator pressure

Conditions: temp:-78.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A suspension of sodium hydride (4.0 g, 100 mmole) in dry tetrahydrofuran (350 mL) under a nitrogen atmosphere was cooled in an ice bath. Pentyl mercaptan (10.8 g, 100 mmole) was added dropwise over 10 minutes. The resulting suspension of sodium alkylmercaptide was added in portions over 30 minutes to a stirred solution of 1-chloro-3-iodopropane (20.44 g, 100 mmole) in tetrahydrofuran (450 mL) that had been cooled to -78° C. The mixture was allowed to warm to ambient temperature overnight, then washed with brine, dried over MgSO4, and concentrated under vacuum. The resultant oil was distilled under water aspirator pressure to yield the desired product (10.67 g, 59% yield), b.p. 113°-119° C. (20 mm Hg). was cooled in an ice bath to warm to ambient temperature overnight washed with brine dried over MgSO4 concentrated under vacuum The resultant oil was distilled under water aspirator pressure

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

Procedure: To a degassed solution of xylene (100 ml) containing 73 (1.82 g, 5.16 mmol), were added 1.25 eq (0.80 ml) of pentane-1-thiol and 1.25 eq of K2CO3 (0.8 g). The resulting mixture was stirred for another 2 hours under N2. Successively were added 10 mol % of Pd2(dba)3 (470 mg) and 20 mol % mmol Xantphos (600 mg). After the addition, the resulting solution was stirred for 18 hours at 130° C. under N2. After cooling to room temperature, the mixture was diluted with ethyl acetate, washed with a saturated NaHCO3 solution, dried (Na2SO4), filtered and concentrated. The resulting residue was purified by flash chromatography (diethyl ether followed by ethyl acetate) to afford 3-[5-pentylsulfanyl-3-(2-trimethylsilanyl-ethoxymethyl)-3H-imidazol-4-yl]-pyridine (74A) as an oil (530 mg, 30%) and starting material (73, 380 mg, 21%), 1H-NMR (400 MHz, CDCl3): δ 9.38 (d, J=2 Hz, 1H), 8.53 (dd, J=5 Hz, 2 Hz, 1H), 8.42 (dt, J=8 Hz, 2 Hz, 1H), 7.82 (s, 1H), 7.35-7.30 (m, 1H), 5.43 (s, 2H), 3.59-3.54 (m, 2H), 2.66 (t, J=7 Hz, 2H), 1.47-1.38 (m, 2H), 1.28-1.10 (m, 4H), 0.96-0.89 (m, 2H), 0.80 (t, J=7 Hz, 3H), 0.0 (s, 9H). After the addition the resulting solution was stirred for 18 hours at 130° C. under N2 washed with a saturated NaHCO3 solution dried (Na2SO4) filtered concentrated The resulting residue was purified by flash chromatography (diethyl ether followed by ethyl acetate)

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

Procedure: The same operation as in Example 1-1 or 1-2 was carried out using trans-2-decenoic acid and 1-pentanethiol as starting materials to give the aimed compound.

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

Procedure: Pentyl mercaptan (0.83 g, 7.9 mmol) was dissolved in tetrahydrofuran (100 ml) and added dropwise to sodium hydride (60% oil, 0.35 g, 8.7 mmol). The reaction mixture was stirred at room temperature for 1 hr. A solution of 2-chloro-6-cyanopyridine (1.00 g, 7.2 mmol) in tetrahydrofuran (10 ml) was added to the mixture, and the mixture was stirred at room temperature for 18 hrs. The reaction mixture was concentrated under reduced pressure, diluted with water and extracted with ethyl acetate. The extract was washed with saturated brine and dried. The solvent was evaporated under reduced pressure to give the titled compound (1.48 g, ca. 100%) as an oil. the mixture was stirred at room temperature for 18 hrs The reaction mixture was concentrated under reduced pressure diluted with water extracted with ethyl acetate The extract was washed with saturated brine dried The solvent was evaporated under reduced pressure

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

Procedure: Pentyl mercaptan (0.83 g, 7.9 mmol) was dissolved in tetrahydrofuran (100 ml) and added dropwise to sodium hydride (60% oil, 0.35 g, 8.7 mmol). The reaction mixture was stirred at room temperature for 1 hr. A solution of 2-chloro-6-cyanopyridine (1.00 g, 7.2 mmol) in tetrahydrofuran (10 ml) was added to the mixture, and the mixture was stirred at room temperature for 18 hrs. The reaction mixture was concentrated under reduced pressure, diluted with water and extracted with ethyl acetate. The extract was washed with saturated brine and dried. The solvent was evaporated under reduced pressure to give the titled compound (1.48 g, ca. 100%) as an oil. the mixture was stirred at room temperature for 18 hrs The reaction mixture was concentrated under reduced pressure diluted with water extracted with ethyl acetate The extract was washed with saturated brine dried The solvent was evaporated under reduced pressure

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

Procedure: To a degassed solution of xylene (100 ml) containing 73 (1.82 g, 5.16 mmol), were added 1.25 eq (0.80 ml) of pentane-1-thiol and 1.25 eq of K2CO3 (0.8 g). The resulting mixture was stirred for another 2 hours under N2. Successively were added 10 mol % of Pd2(dba)3 (470 mg) and 20 mol % mmol Xantphos (600 mg). After the addition, the resulting solution was stirred for 18 hours at 130° C. under N2. After cooling to room temperature, the mixture was diluted with ethyl acetate, washed with a saturated NaHCO3 solution, dried (Na2SO4), filtered and concentrated. The resulting residue was purified by flash chromatography (diethyl ether followed by ethyl acetate) to afford 3-[5-pentylsulfanyl-3-(2-trimethylsilanyl-ethoxymethyl)-3H-imidazol-4-yl]-pyridine (74A) as an oil (530 mg, 30%) and starting material (73, 380 mg, 21%), 1H-NMR (400 MHz, CDCl3): δ 9.38 (d, J=2 Hz, 1H), 8.53 (dd, J=5 Hz, 2 Hz, 1H), 8.42 (dt, J=8 Hz, 2 Hz, 1H), 7.82 (s, 1H), 7.35-7.30 (m, 1H), 5.43 (s, 2H), 3.59-3.54 (m, 2H), 2.66 (t, J=7 Hz, 2H), 1.47-1.38 (m, 2H), 1.28-1.10 (m, 4H), 0.96-0.89 (m, 2H), 0.80 (t, J=7 Hz, 3H), 0.0 (s, 9H). After the addition the resulting solution was stirred for 18 hours at 130° C. under N2 washed with a saturated NaHCO3 solution dried (Na2SO4) filtered concentrated The resulting residue was purified by flash chromatography (diethyl ether followed by ethyl acetate)

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

Procedure: To a degassed solution of xylene (100 ml) containing 73 (1.82 g, 5.16 mmol), were added 1.25 eq (0.80 ml) of pentane-1-thiol and 1.25 eq of K2CO3 (0.8 g). The resulting mixture was stirred for another 2 hours under N2. Successively were added 10 mol % of Pd2(dba)3 (470 mg) and 20 mol % mmol Xantphos (600 mg). After the addition, the resulting solution was stirred for 18 hours at 130° C. under N2. After cooling to room temperature, the mixture was diluted with ethyl acetate, washed with a saturated NaHCO3 solution, dried (Na2SO4), filtered and concentrated. The resulting residue was purified by flash chromatography (diethyl ether followed by ethyl acetate) to afford 3-[5-pentylsulfanyl-3-(2-trimethylsilanyl-ethoxymethyl)-3H-imidazol-4-yl]-pyridine (74A) as an oil (530 mg, 30%) and starting material (73, 380 mg, 21%), 1H-NMR (400 MHz, CDCl3): δ 9.38 (d, J=2 Hz, 1H), 8.53 (dd, J=5 Hz, 2 Hz, 1H), 8.42 (dt, J=8 Hz, 2 Hz, 1H), 7.82 (s, 1H), 7.35-7.30 (m, 1H), 5.43 (s, 2H), 3.59-3.54 (m, 2H), 2.66 (t, J=7 Hz, 2H), 1.47-1.38 (m, 2H), 1.28-1.10 (m, 4H), 0.96-0.89 (m, 2H), 0.80 (t, J=7 Hz, 3H), 0.0 (s, 9H). After the addition the resulting solution was stirred for 18 hours at 130° C. under N2 washed with a saturated NaHCO3 solution dried (Na2SO4) filtered concentrated The resulting residue was purified by flash chromatography (diethyl ether followed by ethyl acetate)

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

Procedure: To a solution of pentanethiol (248 μL, 2.0 mmol) in DMSO (2.5 mL) at 0° C. under nitrogen was added NaH (60% in oil, 80 mg, 2.0 mmol). The suspension was stirred for 0.5 h at 0° C. then treated with 1-(diphenylmethyl)azetidin-3-yl methanesulfonate (317 mg, 1.0 mmol; which may be prepared as described in Step 1) and the mixture allowed to warm to room temperature overnight. Saturated NaHCO3 (5 mL) was added and the mixture was extracted with diethyl ether. The organic layer was separated from the aqueous and the organic washed with brine, dried over Na2SO4 and concentrated to give the product (312 mg, 96%) as a yellow oil. to warm to room temperature overnight the mixture was extracted with diethyl ether The organic layer was separated from the aqueous and the organic washed with brine dried over Na2SO4 concentrated