1-(propyldisulfanyl)propane

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:-20.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: 3-(2,4-Dichlorophenoxy)phenol (0.1 mole) and methylene chloride (200 ml) are charged into a glass reaction vessel equipped with a mechanical stirrer and addition funnel. The mixture is stirred until dissolved and cooled to about -20° C. A solution of propyl sulfenyl chloride freshly prepared by reacting dipropyl disulfide (0.15 mole) with chlorine (0.18 mole) in methylene chloride (100 ml) is then added dropwise to the reaction vessel over a period of about 40 minutes. After the addition is completed stirring is continued for 30 minutes with cooling and 30 minutes at room temperature. After this time the reaction mixture is washed with water (200 ml), with 5% aqueous sodium bicarbonate (200 ml) and again with water (200 ml). The washed solution is then dried by passing it through a phase separator. The dried solution is stripped of solvent under reduced pressure and the residue chromatographed using a clay column and hexane/ethyl acetate as the eluant. The fractions containing the product are combined and stripped of solvent to yield the desired product 5-(2,4-dichlorophenoxy) 2-(propylthio)phenol as the residue. equipped with a mechanical stirrer and addition funnel until dissolved is then added dropwise to the reaction vessel over a period of about 40 minutes After the addition is completed stirring with cooling and 30 minutes at room temperature After this time the reaction mixture is washed with water (200 ml), with 5% aqueous sodium bicarbonate (200 ml) and again with water (200 ml) The washed solution is then dried the residue chromatographed The fractions containing the product

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: Compound 21E was prepared following the procedure as described for the synthesis of compound 21A using (see scheme 3) 1-propyldisulfanyl-propane as the disulfide and 3-(4-bromo-1H-pyrazol-3-yl)-pyridine (compound 20A). (flash chromatography conditions ethyl acetate/diethyl ether 5/1).

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: Compound 21E was prepared following the procedure as described for the synthesis of compound 21A using (see scheme 3) 1-propyldisulfanyl-propane as the disulfide and 3-(4-bromo-1H-pyrazol-3-yl)-pyridine (compound 20A). (flash chromatography conditions ethyl acetate/diethyl ether 5/1).

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: Compound 21E was prepared following the procedure as described for the synthesis of compound 21A using (see scheme 3) 1-propyldisulfanyl-propane as the disulfide and 3-(4-bromo-1H-pyrazol-3-yl)-pyridine (compound 20A). (flash chromatography conditions ethyl acetate/diethyl ether 5/1).

反応条件: temp:-20.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: 3-(2,4-Dichlorophenoxy)phenol (0.1 mole) and methylene chloride (200 ml) are charged into a glass reaction vessel equipped with a mechanical stirrer and addition funnel. The mixture is stirred until dissolved and cooled to about -20° C. A solution of propyl sulfenyl chloride freshly prepared by reacting dipropyl disulfide (0.15 mole) with chlorine (0.18 mole) in methylene chloride (100 ml) is then added dropwise to the reaction vessel over a period of about 40 minutes. After the addition is completed stirring is continued for 30 minutes with cooling and 30 minutes at room temperature. After this time the reaction mixture is washed with water (200 ml), with 5% aqueous sodium bicarbonate (200 ml) and again with water (200 ml). The washed solution is then dried by passing it through a phase separator. The dried solution is stripped of solvent under reduced pressure and the residue chromatographed using a clay column and hexane/ethyl acetate as the eluant. The fractions containing the product are combined and stripped of solvent to yield the desired product 5-(2,4-dichlorophenoxy) 2-(propylthio)phenol as the residue. equipped with a mechanical stirrer and addition funnel until dissolved is then added dropwise to the reaction vessel over a period of about 40 minutes After the addition is completed stirring with cooling and 30 minutes at room temperature After this time the reaction mixture is washed with water (200 ml), with 5% aqueous sodium bicarbonate (200 ml) and again with water (200 ml) The washed solution is then dried the residue chromatographed The fractions containing the product

反応条件: temp:-20.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: 3-(2,4-Dichlorophenoxy)phenol (0.1 mole) and methylene chloride (200 ml) are charged into a glass reaction vessel equipped with a mechanical stirrer and addition funnel. The mixture is stirred until dissolved and cooled to about -20° C. A solution of propyl sulfenyl chloride freshly prepared by reacting dipropyl disulfide (0.15 mole) with chlorine (0.18 mole) in methylene chloride (100 ml) is then added dropwise to the reaction vessel over a period of about 40 minutes. After the addition is completed stirring is continued for 30 minutes with cooling and 30 minutes at room temperature. After this time the reaction mixture is washed with water (200 ml), with 5% aqueous sodium bicarbonate (200 ml) and again with water (200 ml). The washed solution is then dried by passing it through a phase separator. The dried solution is stripped of solvent under reduced pressure and the residue chromatographed using a clay column and hexane/ethyl acetate as the eluant. The fractions containing the product are combined and stripped of solvent to yield the desired product 5-(2,4-dichlorophenoxy) 2-(propylthio)phenol as the residue. equipped with a mechanical stirrer and addition funnel until dissolved is then added dropwise to the reaction vessel over a period of about 40 minutes After the addition is completed stirring with cooling and 30 minutes at room temperature After this time the reaction mixture is washed with water (200 ml), with 5% aqueous sodium bicarbonate (200 ml) and again with water (200 ml) The washed solution is then dried the residue chromatographed The fractions containing the product

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: Compound 21E was prepared following the procedure as described for the synthesis of compound 21A using (see scheme 3) 1-propyldisulfanyl-propane as the disulfide and 3-(4-bromo-1H-pyrazol-3-yl)-pyridine (compound 20A). (flash chromatography conditions ethyl acetate/diethyl ether 5/1).

反応条件: temp:40.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a solution of N-(2-amino-6-methylpyridin-3-ylmethyl)-N-{2-[2-[(2-amino-6-methyl-pyridin-3-ylmethyl)formylamino]-1-(2-hydroxyethyl)-propenyldisulfanyl]-4-hydroxy-1-methylbut-1-enyl}formamide (250 mg, 0.45 mmol) and propyl disulfide (0.21 mL, 1.34 mmol) in methanol (3 ml) was added 1 molar aqueous sodium hydroxide (0.089 mL, 0.089 mmol). The resulting solution was stirred at 35-45° C. for 18 hr. The solution was diluted with water (10 mL) and chloroform (10 mL), but the product remained as a milky insoluble layer. Addition of ethyl acetate (10 mL) and methanol (2 mL) resulted in the formation of two clear layers. The product was contained in the lower layer. This layer was washed with brine (10 mL) dried over sodium sulfate, and evaporated. The residual oil was dissolved in chloroform (1 mL) and chromatographed on silica gel (Waters Sep-Pak 5 g column, using 97.5/2.5 chloroform/methanol as eluent, Fraction size 9 mL). Fractions 4-9 were pooled and evaporated to give 130 mg (41%) of the title compound as nearly colorless oil. MS (LCMS): 356.0 (M+H)+. 1H NMR (CDCl3) δ 0.95 (t, 3H), 1.55 (m, 3H), 1.97 (s, 3H), 2.35 (s, 3H), 2.42 (t, 2H), 2.84 (t, 2H) 3.76 (t, 2H), 5.36 (br. s, 1H), 6.35 (d, 1H), 7.02 (d, 1H), 7.96 (s, 1H). resulted in the formation of two clear layers This layer was washed with brine (10 mL) dried over sodium sulfate evaporated The residual oil was dissolved in chloroform (1 mL) chromatographed on silica gel (Waters Sep-Pak 5 g column, using 97.5/2.5 chloroform/methanol as eluent, Fraction size 9 mL) evaporated

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: Compound 21E was prepared following the procedure as described for the synthesis of compound 21A using (see scheme 3) 1-propyldisulfanyl-propane as the disulfide and 3-(4-bromo-1H-pyrazol-3-yl)-pyridine (compound 20A). (flash chromatography conditions ethyl acetate/diethyl ether 5/1).

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: Compound 21E was prepared following the procedure as described for the synthesis of compound 21A using (see scheme 3) 1-propyldisulfanyl-propane as the disulfide and 3-(4-bromo-1H-pyrazol-3-yl)-pyridine (compound 20A). (flash chromatography conditions ethyl acetate/diethyl ether 5/1).